Gene frequencies

1. Hypophysectomy results in a loss of ability to survive in fresh water by the euryhaline cyprinodont, Fundulus heteroclitus. The average survival time is 6-7 days for salt water-adapted fish. Preadaptation in fresh water before operation may prolong survival but does not prevent ultimate death. 2. Hypophysectomized fish are unable to survive in salinities up to 13 %o. 3. Symptoms of death are those of asthenia accompanied by a slight weight increase, averaging 4.3% in fish not being handled daily. 4. Serum chloride determinations showed that normal fish in either fresh or salt water maintain a uniform level of ca. 0.886 gm.% NaCl. Serum of hypophysectomized fish in salt water is not significantly lower (ca. 0.817 gm.%). Hypophysectomized fish dying in fresh water have only ca. 0.383 gm.%. 5. Replacement therapy with Fundulus pituitary brei enabled hypophysectomized fish to survive in fresh water. Pituitary extract from Perca flavescens, a strictly fresh water species, was partially effective, whereas extracts from glands of Pollachius virens/, a marine species, had no beneficial influence. 6. Injections of ACTH, GH, TSH, thyroxin, DOCA, posterior lobe extract, and an ACTH-GH-TSH combination failed to enable the fish to survive in fresh water. 7. The data presented above appear to indicate that the pituitary of F. heteroclitus secretes an unknown factor(s) which regulates salt balance in that fish in fresh water. This factor is apparently lacking in the stenohaline marine species, P. virens, but may be present in the fresh water species, P. flavescens. 8. Hypophysectomy has no effect on the cytology of the chloride cells either in the active (sea water) or regressed (fresh water) condition. 9. Mucous cells were more abundant in the gills of normal fish when adapted to fresh water than when adapted to salt water. Hypophysectomy resulted in atrophy of the mucous cells in either medium and a decreased abundance in fish dying in fresh water. The abundance and condition of the mucous cells was restored to normal in hypophysectomized fish which were induced to survive in fresh water by injections of Fundulus pituitary brei. 10. The data suggest that the chloride cells are not concerned in the failure of hypophysectomized fish to survive in fresh water, but that atrophy of the mucous cells may be involved.

@article{doi1023071538889,
    author = "BURDEN, CHARLES E.",
    title = "THE FAILURE OF HYPOPHYSECTOMIZED FUNDULUS HETEROCLITUS TO SURVIVE IN FRESH WATER",
    year = "1956",
    journal = "Biological Bulletin",
    abstract = "1. Hypophysectomy results in a loss of ability to survive in fresh water by the euryhaline cyprinodont, Fundulus heteroclitus. The average survival time is 6-7 days for salt water-adapted fish. Preadaptation in fresh water before operation may prolong survival but does not prevent ultimate death. 2. Hypophysectomized fish are unable to survive in salinities up to 13 \%o. 3. Symptoms of death are those of asthenia accompanied by a slight weight increase, averaging 4.3\% in fish not being handled daily. 4. Serum chloride determinations showed that normal fish in either fresh or salt water maintain a uniform level of ca. 0.886 gm.\% NaCl. Serum of hypophysectomized fish in salt water is not significantly lower (ca. 0.817 gm.\%). Hypophysectomized fish dying in fresh water have only ca. 0.383 gm.\%. 5. Replacement therapy with Fundulus pituitary brei enabled hypophysectomized fish to survive in fresh water. Pituitary extract from Perca flavescens, a strictly fresh water species, was partially effective, whereas extracts from glands of Pollachius virens/, a marine species, had no beneficial influence. 6. Injections of ACTH, GH, TSH, thyroxin, DOCA, posterior lobe extract, and an ACTH-GH-TSH combination failed to enable the fish to survive in fresh water. 7. The data presented above appear to indicate that the pituitary of F. heteroclitus secretes an unknown factor(s) which regulates salt balance in that fish in fresh water. This factor is apparently lacking in the stenohaline marine species, P. virens, but may be present in the fresh water species, P. flavescens. 8. Hypophysectomy has no effect on the cytology of the chloride cells either in the active (sea water) or regressed (fresh water) condition. 9. Mucous cells were more abundant in the gills of normal fish when adapted to fresh water than when adapted to salt water. Hypophysectomy resulted in atrophy of the mucous cells in either medium and a decreased abundance in fish dying in fresh water. The abundance and condition of the mucous cells was restored to normal in hypophysectomized fish which were induced to survive in fresh water by injections of Fundulus pituitary brei. 10. The data suggest that the chloride cells are not concerned in the failure of hypophysectomized fish to survive in fresh water, but that atrophy of the mucous cells may be involved.",
    url = "https://doi.org/10.2307/1538889",
    doi = "10.2307/1538889",
    openalex = "W1870182586"
}

The variation in gene frequency among populations or between generations within a population is a result of breeding structure and selection. But breeding structure should affect all loci and alleles in the same way. If there is significant heterogeneity between loci in their apparent inbreeding coefficients F=s(p) (2)/p(1-p), this heterogeneity may be taken as evidence for selection. We have given the statistical properties of F and shown how tests of heterogeneity can be made. Using data from human populations we have shown highly significant heterogeneity in F values for human polymorphic genes over the world, thus demonstrating that a significant fraction of human polymorphisms owe their current gene frequencies to the action of natural selection. We have also applied the method to temporal variation within a population for data on Dacus oleae and have found no significant evidence of selection.

@article{doi101093genetics741175,
    author = "Lewontin, Richard C and Krakauer, Jesse",
    title = "DISTRIBUTION OF GENE FREQUENCY AS A TEST OF THE THEORY OF THE SELECTIVE NEUTRALITY OF POLYMORPHISMS",
    year = "1973",
    journal = "Genetics",
    abstract = "The variation in gene frequency among populations or between generations within a population is a result of breeding structure and selection. But breeding structure should affect all loci and alleles in the same way. If there is significant heterogeneity between loci in their apparent inbreeding coefficients F=s(p) (2)/p(1-p), this heterogeneity may be taken as evidence for selection. We have given the statistical properties of F and shown how tests of heterogeneity can be made. Using data from human populations we have shown highly significant heterogeneity in F values for human polymorphic genes over the world, thus demonstrating that a significant fraction of human polymorphisms owe their current gene frequencies to the action of natural selection. We have also applied the method to temporal variation within a population for data on Dacus oleae and have found no significant evidence of selection.",
    url = "https://doi.org/10.1093/genetics/74.1.175",
    doi = "10.1093/genetics/74.1.175",
    openalex = "W2103286878"
}

Populations of Fundulus heteroclitus, (Cyprinodontidae) a widespread coastal marine fish, were studied in control and artificially heated environments on the North Shore of Long Island, New York to determine (1) patterns of variation in biochemical phenotypes and (2) the extent to which this variation reflected adaptation to environmental characteristics. Variation at three of twelve polymorphic isoenzyme loci from the warm water population was beyond the range of variation among control populations, and resembled those determined for populations living at more southern latitudes. Hence, these differences were interpreted as adaptations to warm environments. Significant differences in allele frequencies and zygotic proportions at ten of twelve isoenzyme loci were found associated with differences in environments, sexes, and/or age classes. These data strongly support the view that protein polymorphisms are adaptive. Several observations suggested that selection acts upon multilocus phenotypes rather than upon those of single loci. Several di-locus phenotypic distributions were demonstrated to be nonrandom, and those that exhibited similar patterns of dependence over years were postulated to be maintained by selection. Highly heterozygous fish exhibited superior viability when cohorts were compared over successive years. The consequences of the polygynous mating system in this species for maintaining genetic variation and for allowing rapid evolutionary response to a variable environment are discussed.

@article{doi101093genetics79197,
    author = "Mitton, Jeffry B. and Koehn, Richard K.",
    title = "GENETIC ORGANIZATION AND ADAPTIVE RESPONSE OF ALLOZYMES TO ECOLOGICAL VARIABLES IN FUNDULUS HETEROCLITUS",
    year = "1975",
    journal = "Genetics",
    abstract = "Populations of Fundulus heteroclitus, (Cyprinodontidae) a widespread coastal marine fish, were studied in control and artificially heated environments on the North Shore of Long Island, New York to determine (1) patterns of variation in biochemical phenotypes and (2) the extent to which this variation reflected adaptation to environmental characteristics. Variation at three of twelve polymorphic isoenzyme loci from the warm water population was beyond the range of variation among control populations, and resembled those determined for populations living at more southern latitudes. Hence, these differences were interpreted as adaptations to warm environments. Significant differences in allele frequencies and zygotic proportions at ten of twelve isoenzyme loci were found associated with differences in environments, sexes, and/or age classes. These data strongly support the view that protein polymorphisms are adaptive. Several observations suggested that selection acts upon multilocus phenotypes rather than upon those of single loci. Several di-locus phenotypic distributions were demonstrated to be nonrandom, and those that exhibited similar patterns of dependence over years were postulated to be maintained by selection. Highly heterozygous fish exhibited superior viability when cohorts were compared over successive years. The consequences of the polygynous mating system in this species for maintaining genetic variation and for allowing rapid evolutionary response to a variable environment are discussed.",
    url = "https://doi.org/10.1093/genetics/79.1.97",
    doi = "10.1093/genetics/79.1.97",
    openalex = "W2137118500"
}

@article{doi101007bf00484222,
    author = "Powers, Dennis A. and Place, Allen R.",
    title = "Biochemical genetics of Fundulus heteroclitus (L.). I. Temporal and spatial variation in gene frequencies of Ldh-B, Mdh-A, Gpi-B, and Pgm-A",
    year = "1978",
    journal = "Biochemical Genetics",
    url = "https://doi.org/10.1007/bf00484222",
    doi = "10.1007/bf00484222",
    openalex = "W2019968569",
    references = "doi101001jama195102920260071031, doi101093aibsbulletin2214b, doi101093genetics762379, doi101111j146918091937tb02153x, doi101111j155856461975tb00851x, doi1015159780691209418, doi1023072407692, doi102307jctvx5wbbh, openalexw2062594085"
}

@article{powers1978biochemical,
    author = "Powers, Dennis A. and Place, Allen R.",
    title = "Biochemical genetics of Fundulus heteroclitus (L.). I. Temporal and spatial variation in gene frequencies of Ldh-B, Mdh-A, Gpi-B, and Pgm-A",
    year = "1978",
    journal = "Biochemical Genetics",
    url = "https://doi.org/10.1007/bf00484222",
    doi = "10.1007/bf00484222",
    number = "5-6",
    openalex = "W2019968569",
    pages = "593-607",
    volume = "16",
    references = "doi101001jama195102920260071031, doi101093aibsbulletin2214b, doi101093genetics762379, doi101111j146918091937tb02153x, doi101111j155856461975tb00851x, doi1015159780691209418, doi1023072407692, doi102307jctvx5wbbh, openalexw2062594085"
}

@misc{powers1978biochemical1,
    author = "Powers, D. A. and Place, A. R",
    title = "Biochemical genetics of Fundulus heteroclitus (L.). 1. Temporal and spatial variation in gene frequencies of Ldh-B, Mdh-A, Gpi-B and Pgm-A",
    year = "1978",
    howpublished = "Biochemical Genetics, v. 16, p. 593-607",
    note = "talkorigins\_source = {true}; raw\_reference = {Powers, D. A., and Place, A. R., 1978, Biochemical genetics of Fundulus heteroclitus (L.). 1. Temporal and spatial variation in gene frequencies of Ldh-B, Mdh-A, Gpi-B and Pgm-A: Biochemical Genetics, v. 16, p. 593-607.}"
}

In order to evaluate whether functional differences exist between allelic variants of a B type lactate dehydrogenase (LDH; L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) in the teleost fish Fundulus heteroclitus (Linnaeus), the kinetic properties of pyruvate reduction were examined. While the pH dependence and the temperature dependence for maximal catalysis were indistinguishable among the allozymes, reaction velocities at low pyruvate concentrations were significantly different. At pH values below 8.00, the LDH-BbBb allozyme showed a greater reaction rate at lower temperatures (e.g., 10 degrees C) than LDH-BaBa. The phenomenon was reversed at higher temperatures (e.g., greater than 25 degrees C) for pH values between 6.50 and 7.00. The rates for the heterozygous phenotype, LDH-BaBb, were not the arithmetic average of the two homotetrameric allozymes. When reaction rates were compared at constant relative alkalinity, that is, a constant [OH-]/[H+] ratio, the findings were similar. The differences in the temperature dependence and the pH dependence for pyruvate reduction found between the LDH-B allozymes may reflect a selective adaptation and help explain the geographical variation in the Ldh-B gene frequencies of F. heteroclitus.

@article{doi101073pnas7652354,
    author = "Place, Allen R. and Powers, Dennis A.",
    title = "Genetic variation and relative catalytic efficiencies: lactate dehydrogenase B allozymes of Fundulus heteroclitus.",
    year = "1979",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = "In order to evaluate whether functional differences exist between allelic variants of a B type lactate dehydrogenase (LDH; L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) in the teleost fish Fundulus heteroclitus (Linnaeus), the kinetic properties of pyruvate reduction were examined. While the pH dependence and the temperature dependence for maximal catalysis were indistinguishable among the allozymes, reaction velocities at low pyruvate concentrations were significantly different. At pH values below 8.00, the LDH-BbBb allozyme showed a greater reaction rate at lower temperatures (e.g., 10 degrees C) than LDH-BaBa. The phenomenon was reversed at higher temperatures (e.g., greater than 25 degrees C) for pH values between 6.50 and 7.00. The rates for the heterozygous phenotype, LDH-BaBb, were not the arithmetic average of the two homotetrameric allozymes. When reaction rates were compared at constant relative alkalinity, that is, a constant [OH-]/[H+] ratio, the findings were similar. The differences in the temperature dependence and the pH dependence for pyruvate reduction found between the LDH-B allozymes may reflect a selective adaptation and help explain the geographical variation in the Ldh-B gene frequencies of F. heteroclitus.",
    url = "https://doi.org/10.1073/pnas.76.5.2354",
    doi = "10.1073/pnas.76.5.2354",
    openalex = "W2059454129",
    references = "doi1010160003269764902003, doi1010160160932778900819, doi101016b9780120913046x50010, doi101042bj1390715, doi101042bj1390721, doi101111j155856461975tb00851x, doi1013182nse61a15616, doi1023072407274, openalexw1889077695, openalexw1964262399"
}

@article{cashon1981biochemical,
    author = "Cashon, Robert E. and Van Beneden, Rebecca J. and Powers, Dennis A.",
    title = "Biochemical genetics of Fundulus heteroclitus (L.). IV. Spatial variation in gene frequencies of Idh-A, Idh-B, 6-Pgdh-A, and Est-S",
    year = "1981",
    journal = "Biochemical Genetics",
    url = "https://doi.org/10.1007/bf00484004",
    doi = "10.1007/bf00484004",
    number = "7-8",
    openalex = "W2091365386",
    pages = "715-728",
    volume = "19",
    references = "doi101007bf00391612, doi1010160040580978900394, doi101038hdy197489, doi101073pnas7652354, doi101111j155856461975tb00851x, doi1023071442526, doi1023071935311, doi1023072407274, doi1023072407692, powers1978biochemical"
}

Adenosine triphosphate levels in erythrocytes are correlated with LDH-B genotype in Fundulus heteroclitus. Adenosine triphosphate is the fish's allosteric modifier of hemoglobin oxygen affinity. Since oxygen delivery to muscle affects swimming performance, fish of each homozygous LDH-B phenotype were swum to exhaustion at 10 degrees or 25 degrees C to determine whether in vitro differences attributed to the LDH-B allelic isozymes were manifest in vivo. At 10 degrees C, the critical swimming speed of the LDH-BaBa phenotype was 3.6 body lengths per second, whereas that of the LDH-BbBb phenotype was 4.3 body lengths per second. At 25 degrees C there were no differences between LDH-B phenotypes in erythrocyte adenosine triphosphate levels, blood oxygen affinity, or swimming performance.

@article{doi101126science7079747,
    author = "DiMichele, Leonard and Powers, Dennis A.",
    title = "Physiological Basis for Swimming Endurance Differences Between LDH-B Genotypes of Fundulus heteroclitus",
    year = "1982",
    journal = "Science",
    abstract = "Adenosine triphosphate levels in erythrocytes are correlated with LDH-B genotype in Fundulus heteroclitus. Adenosine triphosphate is the fish's allosteric modifier of hemoglobin oxygen affinity. Since oxygen delivery to muscle affects swimming performance, fish of each homozygous LDH-B phenotype were swum to exhaustion at 10 degrees or 25 degrees C to determine whether in vitro differences attributed to the LDH-B allelic isozymes were manifest in vivo. At 10 degrees C, the critical swimming speed of the LDH-BaBa phenotype was 3.6 body lengths per second, whereas that of the LDH-BbBb phenotype was 4.3 body lengths per second. At 25 degrees C there were no differences between LDH-B phenotypes in erythrocyte adenosine triphosphate levels, blood oxygen affinity, or swimming performance.",
    url = "https://doi.org/10.1126/science.7079747",
    doi = "10.1126/science.7079747",
    openalex = "W2023346689"
}

In order to evaluate whether functional differences exist between allelic variants (allozymes) of the B-type lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) in the fish Fundulus heteroclitus, the kinetic properties were examined. Differences in product inhibition between allelic isozymes were observed. LDH-Bb4 was found to be inhibited by lower concentrations of both lactate and pyruvate than either LDH-Ba/Bb or LDH-Ba4. While the pH and temperature dependence for maximal catalysis (Vmax) in both the forward and reverse directions were indistinguishable among the allozymes, reaction velocities at low substrate concentrations (Vmax/Km) were significantly different. These differences could be explained by LDH-Bb4 having a greater substrate affinity than LDH-Ba4 at cold temperatures while the reverse was true at elevated temperatures. At a given pH, LDH-Bb4 showed a greater reaction rate at lower temperatures (e.g. 10 degrees C) than LDH-Ba4. The phenomenon was reversed at higher temperatures (e.g. greater than 35 degrees C). When reaction rates were compared at constant relative alkalinity, that is, a constant [OH-]/[H+] ratio, similar findings were obtained. The response for the heterozygous allozyme, LDH-Ba/Bb, was not the arithmetic average of the two homotetrameric allozymes. The biological significance of these allozymic differences is discussed.

@article{doi101016s0021925817436040,
    author = "Place, Allen R. and Powers, Dennis A.",
    title = "Kinetic characterization of the lactate dehydrogenase (LDH-B4) allozymes of Fundulus heteroclitus.",
    year = "1984",
    journal = "Journal of Biological Chemistry",
    abstract = "In order to evaluate whether functional differences exist between allelic variants (allozymes) of the B-type lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) in the fish Fundulus heteroclitus, the kinetic properties were examined. Differences in product inhibition between allelic isozymes were observed. LDH-Bb4 was found to be inhibited by lower concentrations of both lactate and pyruvate than either LDH-Ba/Bb or LDH-Ba4. While the pH and temperature dependence for maximal catalysis (Vmax) in both the forward and reverse directions were indistinguishable among the allozymes, reaction velocities at low substrate concentrations (Vmax/Km) were significantly different. These differences could be explained by LDH-Bb4 having a greater substrate affinity than LDH-Ba4 at cold temperatures while the reverse was true at elevated temperatures. At a given pH, LDH-Bb4 showed a greater reaction rate at lower temperatures (e.g. 10 degrees C) than LDH-Ba4. The phenomenon was reversed at higher temperatures (e.g. greater than 35 degrees C). When reaction rates were compared at constant relative alkalinity, that is, a constant [OH-]/[H+] ratio, similar findings were obtained. The response for the heterozygous allozyme, LDH-Ba/Bb, was not the arithmetic average of the two homotetrameric allozymes. The biological significance of these allozymic differences is discussed.",
    url = "https://doi.org/10.1016/s0021-9258(17)43604-0",
    doi = "10.1016/s0021-9258(17)43604-0",
    openalex = "W1515088892"
}

Starch gel electrophoresis has shown that natural populations of Fundulus heteroclitus have electrophoretic variants for at least 21 loci. We provide inheritance data for 10 polymorphic systems: esterases (Est-B, EST-C, and Est-D); aspartate amlnotransferases (Aat-A, and Aat-B); mannosephosphate isomerase (Mpl-A); acid phosphatase (Ap-A); phosphoglucomutase (Pgm-B); hexose-6-phosphate dehydrogenase (H6pdh-A); and fumarase (Fum-A). Variants for nine of these loci segregate as autosomally inherited codominant alleles. The other system, EST-C, does not reflect such inheritance. We have identified two possible linkage groups: H6pdh-A may be loosely linked to Pgm-B, and Fum-A appears to be linked to Pgm-A. Tissue specificity and intracellular localization for all these loci are also presented.

@article{brown1988biochemical,
    author = "Brown, D. C. and Ropson, I. J. and Powers, D. A.",
    title = "Biochemical Genetics of Fundulus heteroclitus (L.): V. Inheritance of 10 Biochemical Loci",
    year = "1988",
    journal = "Journal of Heredity",
    abstract = "Starch gel electrophoresis has shown that natural populations of Fundulus heteroclitus have electrophoretic variants for at least 21 loci. We provide inheritance data for 10 polymorphic systems: esterases (Est-B, EST-C, and Est-D); aspartate amlnotransferases (Aat-A, and Aat-B); mannosephosphate isomerase (Mpl-A); acid phosphatase (Ap-A); phosphoglucomutase (Pgm-B); hexose-6-phosphate dehydrogenase (H6pdh-A); and fumarase (Fum-A). Variants for nine of these loci segregate as autosomally inherited codominant alleles. The other system, EST-C, does not reflect such inheritance. We have identified two possible linkage groups: H6pdh-A may be loosely linked to Pgm-B, and Fum-A appears to be linked to Pgm-A. Tissue specificity and intracellular localization for all these loci are also presented.",
    url = "https://doi.org/10.1093/oxfordjournals.jhered.a110528",
    doi = "10.1093/oxfordjournals.jhered.a110528",
    number = "5",
    openalex = "W2278152654",
    pages = "359-365",
    volume = "79"
}

At the extremes of its natural distribution, populations of the common killifish Fundulus heteroclitus experience a difference of more than 15 degrees C in mean annual temperature. These populations are virtually fixed for two different codominant alleles at the heart-type lactate dehydrogenase locus (Ldh-B) which code for allozymes with different and adaptive kinetic responses to temperature. Two populations near the extremes of the species range (i.e., Maine and Georgia) were further studied for thermal adaptation at this locus. In the absence of any kinetic differences one would predict that to maintain a constant reaction velocity, 2 to 3 times as much enzyme would be required for each 10 degrees C decrease in environmental temperature. Consistent with this adaptive strategy and in addition to the adaptive kinetic characteristics, the LDH-B4 enzyme (EC 1.1.1.27) concentration and its mRNA concentration were approximately twice as great in the northern population as in the southern population. Acclimation experiments allow us to conclude that these differences are due to a combination of fixed genetic traits (evolutionary adaptation) and plastic responses to temperature (physiological acclimation). Furthermore, our calculations show that the LDH-B4 reaction velocities are essentially equivalent for these two populations, even though they live in significantly different thermal environments.

@article{doi101073pnas86239365,
    author = "Crawford, D. L. and Powers, Dennis A.",
    title = "Molecular basis of evolutionary adaptation at the lactate dehydrogenase-B locus in the fish Fundulus heteroclitus.",
    year = "1989",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = "At the extremes of its natural distribution, populations of the common killifish Fundulus heteroclitus experience a difference of more than 15 degrees C in mean annual temperature. These populations are virtually fixed for two different codominant alleles at the heart-type lactate dehydrogenase locus (Ldh-B) which code for allozymes with different and adaptive kinetic responses to temperature. Two populations near the extremes of the species range (i.e., Maine and Georgia) were further studied for thermal adaptation at this locus. In the absence of any kinetic differences one would predict that to maintain a constant reaction velocity, 2 to 3 times as much enzyme would be required for each 10 degrees C decrease in environmental temperature. Consistent with this adaptive strategy and in addition to the adaptive kinetic characteristics, the LDH-B4 enzyme (EC 1.1.1.27) concentration and its mRNA concentration were approximately twice as great in the northern population as in the southern population. Acclimation experiments allow us to conclude that these differences are due to a combination of fixed genetic traits (evolutionary adaptation) and plastic responses to temperature (physiological acclimation). Furthermore, our calculations show that the LDH-B4 reaction velocities are essentially equivalent for these two populations, even though they live in significantly different thermal environments.",
    url = "https://doi.org/10.1073/pnas.86.23.9365",
    doi = "10.1073/pnas.86.23.9365",
    openalex = "W2034334508",
    references = "cashon1981biochemical, doi101002jez1402010102, doi1010079781461263302, doi1010160003269783904189, doi1010160003986177903460, doi101016s0021925817436040, doi101021bi00591a005, doi101073pnas74104562, doi101073pnas7652354, doi101126science7079747, powers1978biochemical"
}

@article{duggins1989biochemical,
    author = "Duggins, Charles F. and Relyea, Kenneth G. and Karlin, Alvan A.",
    title = "Biochemical Systematics in Southeastern Populations of Fundulus heteroclitus and Fundulus grandis",
    year = "1989",
    journal = "Northeast Gulf Science",
    url = "https://doi.org/10.18785/negs.1002.03",
    doi = "10.18785/negs.1002.03",
    number = "2",
    openalex = "W2804340583",
    volume = "10",
    references = "doi101007bf00121817, doi1010160305197883900662, doi101093oxfordjournalsjhereda109497, doi105479si00963801983229215, doi1058782flmnhtlym5013, openalexw106653420"
}

Geographic variation in the gene frequencies corresponding to 15 polymorphic enzymes were studied in the common killifish Fundulus heteroclitus. Aat-A, Est-B, Fum-A, H6pdh-A, Mpi-A and Pgm-B showed clinal variation in allelic frequencies along the Atlantic coast of North America, while Aat-B, Ap-A, and the EST-C phenotypes did not. The clinal allelic variation of six previously examined loci (Ldh-B, Mdh-A, Gpi-B, Idh-A, Pgm-A, and 6-Pgdh-A) was extended to locations farther north. Gene diversity was lowest in the cold waters of northern latitudes and highest in the warmer waters of southern latitudes. The variety of clinal shapes and widths suggests that selection has affected the allelic distributions for at least some of these loci. This hypothesis is discussed with regard to the range contractions and extensions caused by the glacial advances and retreats during the Pleistocene.

@article{doi101111j155856461990tb04276x,
    author = "Ropson, Ira J. and ew C. Brown and Powers, Dennis A.",
    title = "BIOCHEMICAL GENETICS OF FUNDULUS HETEROCLITUS (L.). VI. GEOGRAPHICAL VARIATION IN THE GENE FREQUENCIES OF 15 LOCI",
    year = "1990",
    journal = "Evolution",
    abstract = "Geographic variation in the gene frequencies corresponding to 15 polymorphic enzymes were studied in the common killifish Fundulus heteroclitus. Aat-A, Est-B, Fum-A, H6pdh-A, Mpi-A and Pgm-B showed clinal variation in allelic frequencies along the Atlantic coast of North America, while Aat-B, Ap-A, and the EST-C phenotypes did not. The clinal allelic variation of six previously examined loci (Ldh-B, Mdh-A, Gpi-B, Idh-A, Pgm-A, and 6-Pgdh-A) was extended to locations farther north. Gene diversity was lowest in the cold waters of northern latitudes and highest in the warmer waters of southern latitudes. The variety of clinal shapes and widths suggests that selection has affected the allelic distributions for at least some of these loci. This hypothesis is discussed with regard to the range contractions and extensions caused by the glacial advances and retreats during the Pleistocene.",
    url = "https://doi.org/10.1111/j.1558-5646.1990.tb04276.x",
    doi = "10.1111/j.1558-5646.1990.tb04276.x",
    openalex = "W2326890067",
    references = "brown1988biochemical"
}

Fundulus heteroclitus is a highly polymorphic fish distributed along the Atlantic coast of North America. Several loci show directional changes in gene frequency with latitude (i.e., clines). Such directional changes have classically been described by two general models: primary and secondary intergradation. Previously, it has not been possible to distinguish between these models for Fundulus heteroclitus on the basis of allelic isozymes or morphological data. However, recent analysis of mitochondrial-DNA (mtDNA) restriction electromorphs helps resolve this issue. Mitochondrial-DNA samples from 48 individuals representing four populations were digested with 17 restriction endonucleases. After electrophoresis, the sizes of the mtDNA fragments were used to analyze the phylogenetic relatedness of fish collected over most of the species range. The analysis clearly identified two major races within the species: a northern and a southern form. The distribution of the mtDNA electromorphs, combined with zoogeographical changes in allelic isozymes and in eggs and adult morphologies (published elsewhere), makes the secondary-intergradation hypothesis most compelling.

@article{doi101111j155856461990tb04277x,
    author = "González‐Villaseñor, Lucia Irene and Powers, Dennis A.",
    title = "MITOCHONDRIAL‐DNA RESTRICTION‐SITE POLYMORPHISMS IN THE TELEOST FUNDULUS HETEROCLITUS SUPPORT SECONDARY INTERGRADATION",
    year = "1990",
    journal = "Evolution",
    abstract = "Fundulus heteroclitus is a highly polymorphic fish distributed along the Atlantic coast of North America. Several loci show directional changes in gene frequency with latitude (i.e., clines). Such directional changes have classically been described by two general models: primary and secondary intergradation. Previously, it has not been possible to distinguish between these models for Fundulus heteroclitus on the basis of allelic isozymes or morphological data. However, recent analysis of mitochondrial-DNA (mtDNA) restriction electromorphs helps resolve this issue. Mitochondrial-DNA samples from 48 individuals representing four populations were digested with 17 restriction endonucleases. After electrophoresis, the sizes of the mtDNA fragments were used to analyze the phylogenetic relatedness of fish collected over most of the species range. The analysis clearly identified two major races within the species: a northern and a southern form. The distribution of the mtDNA electromorphs, combined with zoogeographical changes in allelic isozymes and in eggs and adult morphologies (published elsewhere), makes the secondary-intergradation hypothesis most compelling.",
    url = "https://doi.org/10.1111/j.1558-5646.1990.tb04277.x",
    doi = "10.1111/j.1558-5646.1990.tb04277.x",
    openalex = "W2312265334",
    references = "brown1988biochemical, doi101007bf01734101, doi1010160307441283900687, doi101073pnas76105269, doi101073pnas7641967, doi101111j146918091937tb02153x, doi101146annureves18110187001413, doi101146annureves18110187002421, doi1023072407738, doi104159harvard9780674865327, openalexw2144634347"
}

@article{ropson1990biochemical,
    author = "Ropson, Ira J. and Brown, Drew C. and Powers, Dennis A.",
    title = "Biochemical Genetics of Fundulus heteroclitus (L.). VI. Geographical Variation in the Gene Frequencies of 15 Loci",
    year = "1990",
    journal = "Evolution",
    url = "https://doi.org/10.2307/2409521",
    doi = "10.2307/2409521",
    number = "1",
    openalex = "W4252252776",
    pages = "16",
    volume = "44"
}

Gulf of Mexico versus Atlantic populations of several coastal species in the southeastern United States are known to differ sharply in genetic composition, but most transitional zones have not previously been examined in detail. Here we employ molecular markers from mitochondrial and nuclear loci to characterize cytonuclear genetic associations at meso- and microgeographic scales along an eastern Florida transitional zone between genetically distinct Atlantic and Gulf populations of the American oyster, Crassostrea virginica. The single- and multilocus cytonuclear patterns display: (1) a cline extending along 340 km of the east Florida coastline; (2) a pronounced step in the cline centered at Cape Canaveral (shifts in allelic frequencies by 50-75% over a 20 km distance); (3) a close agreement of observed genotypic frequencies with Hardy-Weinberg expectations within locales; and (4) mild or nonexistent nuclear and cytonuclear disequilibria in most local population samples. These results imply: (1) considerable restrictions to interpopulational gene flow along the eastern Florida coastline; (2) within locales, free interbreeding (as opposed to mere population admixture) between Gulf and Atlantic forms of oysters; and (3) localized population recruitment in the transition zone localities. These findings demonstrate that marine organisms with high dispersal potential via long-lived pelagic larvae can nonetheless display pronounced spatial population genetic structure, and more generally they exemplify the utility of pronounced genetic transition zones for the study of population level processes.

@article{doi101111j155856461996tb03618x,
    author = "Hare, Matthew P. and Avise, John C.",
    title = "MOLECULAR GENETIC ANALYSIS OF A STEPPED MULTILOCUS CLINE IN THE AMERICAN OYSTER (CRASSOSTREA VIRGINICA)",
    year = "1996",
    journal = "Evolution",
    abstract = "Gulf of Mexico versus Atlantic populations of several coastal species in the southeastern United States are known to differ sharply in genetic composition, but most transitional zones have not previously been examined in detail. Here we employ molecular markers from mitochondrial and nuclear loci to characterize cytonuclear genetic associations at meso- and microgeographic scales along an eastern Florida transitional zone between genetically distinct Atlantic and Gulf populations of the American oyster, Crassostrea virginica. The single- and multilocus cytonuclear patterns display: (1) a cline extending along 340 km of the east Florida coastline; (2) a pronounced step in the cline centered at Cape Canaveral (shifts in allelic frequencies by 50-75\% over a 20 km distance); (3) a close agreement of observed genotypic frequencies with Hardy-Weinberg expectations within locales; and (4) mild or nonexistent nuclear and cytonuclear disequilibria in most local population samples. These results imply: (1) considerable restrictions to interpopulational gene flow along the eastern Florida coastline; (2) within locales, free interbreeding (as opposed to mere population admixture) between Gulf and Atlantic forms of oysters; and (3) localized population recruitment in the transition zone localities. These findings demonstrate that marine organisms with high dispersal potential via long-lived pelagic larvae can nonetheless display pronounced spatial population genetic structure, and more generally they exemplify the utility of pronounced genetic transition zones for the study of population level processes.",
    url = "https://doi.org/10.1111/j.1558-5646.1996.tb03618.x",
    doi = "10.1111/j.1558-5646.1996.tb03618.x",
    openalex = "W2061179033",
    references = "duggins1989biochemical"
}

1. Experiments were designed to reveal geographic differentiation, and its evolutionary significance, in early life-history characters of Fundulus heteroclitus. The inherited capacity for growth was studied for five populations, from South Carolina to Maine, USA, at three temperatures representative of field conditions. Two generations of newly hatched fish were reared and tested. The second generation of fish was produced from parents that were themselves reared in the laboratory, in order to control for maternally transmitted environmental effects. 2. Over the first three weeks post-hatch, individuals from northern populations grew more rapidly than those from southern populations at higher temperatures (21 and 28 °C) whereas there were generally no differences among populations at the lowest temperature (17 °C). 3. The results do not conform to thermal adaptation models, in which northern populations are expected to show higher growth rates than southern populations at cold temperatures, and vice versa at higher temperatures. Instead, the higher growth rate of northern fish is interpreted as an adaptation to a short growing season. This represents an example of countergradient variation, in that genetic influences favouring rapid growth at high latitudes oppose the environmental effect of a shorter growing season. The cline of growth rates is concordant with morphological, behavioural and genetic contrasts between subspecies of Fundulus heteroclitus.

@article{doi1023072390285,
    author = "Schultz, Eric T. and Reynolds, K. E. and Conover, David O.",
    title = "Countergradient Variation in Growth Among Newly Hatched Fundulus Heteroclitus: Geographic Differences Revealed by Common-Environment Experiments",
    year = "1996",
    journal = "Functional Ecology",
    abstract = "1. Experiments were designed to reveal geographic differentiation, and its evolutionary significance, in early life-history characters of Fundulus heteroclitus. The inherited capacity for growth was studied for five populations, from South Carolina to Maine, USA, at three temperatures representative of field conditions. Two generations of newly hatched fish were reared and tested. The second generation of fish was produced from parents that were themselves reared in the laboratory, in order to control for maternally transmitted environmental effects. 2. Over the first three weeks post-hatch, individuals from northern populations grew more rapidly than those from southern populations at higher temperatures (21 and 28 °C) whereas there were generally no differences among populations at the lowest temperature (17 °C). 3. The results do not conform to thermal adaptation models, in which northern populations are expected to show higher growth rates than southern populations at cold temperatures, and vice versa at higher temperatures. Instead, the higher growth rate of northern fish is interpreted as an adaptation to a short growing season. This represents an example of countergradient variation, in that genetic influences favouring rapid growth at high latitudes oppose the environmental effect of a shorter growing season. The cline of growth rates is concordant with morphological, behavioural and genetic contrasts between subspecies of Fundulus heteroclitus.",
    url = "https://doi.org/10.2307/2390285",
    doi = "10.2307/2390285",
    openalex = "W2089469721",
    references = "cashon1981biochemical, doi101007bf00317554, doi101016s0169534700890813, doi101086410622, doi101111j155856461982tb05466x, doi101139f88197, doi101139f91065, doi102307jctvx5wbbh, doi102960jv8a6, openalexw1538205139, openalexw2047770073"
}

Gulf of Mexico versus Atlantic populations of several coastal species in the southeastern United States are known to differ sharply in genetic composition, but most transitional zones have not previously been examined in detail.Here we employ molecular markers from mitochondrial and nuclear loci to characterize cytonuclear genetic associations at meso-and microgeographic scales along an eastern Florida transitional zone between genetically distinct Atlantic and Gulf populations of the American oyster, Crassostrea virginica.The single-and multilocus cytonuclear patterns display: (1) a cline extending along 340 km of the east Florida coastline; (2) a pronounced step in the cline centered at Cape Canaveral (shifts in allelic frequencies by 50-75% over a 20 km distance); (3) a close agreement of observed genotypic frequencies with Hardy-Weinberg expectations within locales; and (4) mild or nonexistent nuclear and cytonuclear disequilibria in most local population samples.These results imply: (1) considerable restrictions to interpopulational gene flow along the eastern Florida coastline; (2) within locales, free interbreeding (as opposed to mere population admixture) between Gulf and Atlantic forms of oysters; and (3) localized population recruitment in the transition zone localities.These findings demonstrate that marine organisms with high dispersal potential via long-lived pelagic larvae can nonetheless display pronounced spatial population genetic structure, and more generally they exemplify the utility of pronounced genetic transition zones for the study of population level processes.

@article{doi1023072410699,
    author = "Hare, Matthew P. and Avise, John C.",
    title = "Molecular Genetic Analysis of a Stepped Multilocus Cline in the American Oyster (Crassostrea virginica)",
    year = "1996",
    journal = "Evolution",
    abstract = "Gulf of Mexico versus Atlantic populations of several coastal species in the southeastern United States are known to differ sharply in genetic composition, but most transitional zones have not previously been examined in detail.Here we employ molecular markers from mitochondrial and nuclear loci to characterize cytonuclear genetic associations at meso-and microgeographic scales along an eastern Florida transitional zone between genetically distinct Atlantic and Gulf populations of the American oyster, Crassostrea virginica.The single-and multilocus cytonuclear patterns display: (1) a cline extending along 340 km of the east Florida coastline; (2) a pronounced step in the cline centered at Cape Canaveral (shifts in allelic frequencies by 50-75\% over a 20 km distance); (3) a close agreement of observed genotypic frequencies with Hardy-Weinberg expectations within locales; and (4) mild or nonexistent nuclear and cytonuclear disequilibria in most local population samples.These results imply: (1) considerable restrictions to interpopulational gene flow along the eastern Florida coastline; (2) within locales, free interbreeding (as opposed to mere population admixture) between Gulf and Atlantic forms of oysters; and (3) localized population recruitment in the transition zone localities.These findings demonstrate that marine organisms with high dispersal potential via long-lived pelagic larvae can nonetheless display pronounced spatial population genetic structure, and more generally they exemplify the utility of pronounced genetic transition zones for the study of population level processes.",
    url = "https://doi.org/10.2307/2410699",
    doi = "10.2307/2410699",
    openalex = "W4254810384",
    references = "duggins1989biochemical"
}

We have used an experimentally based strategy to address molecular mechanisms underlying adaptation in Fundulus heteroclitus. In an attempt to falsify the hypothesis that selection is a major driving force in the maintenance of genetic diversity, we employed a multidisciplinary approach including allelic isozyme and mtDNA phylogeography, kinetic analyses of allelic isozymes, analysis of variation in coding and regulatory DNA sequences, metabolic biochemistry, organismal physiology, and selection experiments. Observed differences in gene structure and expression led us to make testable predictions about differences in metabolic flux, whole organism performance, and differential survival between allotypes. We have shown that variation in the lactate dehydrogenase-B (Ldh-B) protein results in differences in physiological function and is correlated with differences in survival at high temperatures. Recent work has investigated the role of variation in Ldh-B expression. There are differences in the levels of Ldh-B protein, mRNA, and transcription rate. We have addressed the mechanisms responsible for differences in transcription rate by a combination of sequence comparison, DNase I footprinting, and functional analyses both in vitro and in vivo. We have shown that variation in the regulatory sequence of Ldh-B is responsible for the differences in transcription rate between populations and that the patterns of variation are inconsistent with a neutral model of molecular evolution. This functional differentiation, coupled with departures from neutral expectations, suggests that natural selection has acted on the regulation of Ldh-B. This article illustrates the value of a multidisciplinary approach in addressing problems in gene structure, expression, and evolutionary adaptation.

@article{doi101002sici1097010x199809102821271aidjez1130co2j,
    author = "Powers, Dennis A. and Schulte, Patricia M.",
    title = "Evolutionary adaptations of gene structure and expression in natural populations in relation to a changing environment: A multidisciplinary approach to address the million-year saga of a small fish",
    year = "1998",
    journal = "Journal of Experimental Zoology",
    abstract = "We have used an experimentally based strategy to address molecular mechanisms underlying adaptation in Fundulus heteroclitus. In an attempt to falsify the hypothesis that selection is a major driving force in the maintenance of genetic diversity, we employed a multidisciplinary approach including allelic isozyme and mtDNA phylogeography, kinetic analyses of allelic isozymes, analysis of variation in coding and regulatory DNA sequences, metabolic biochemistry, organismal physiology, and selection experiments. Observed differences in gene structure and expression led us to make testable predictions about differences in metabolic flux, whole organism performance, and differential survival between allotypes. We have shown that variation in the lactate dehydrogenase-B (Ldh-B) protein results in differences in physiological function and is correlated with differences in survival at high temperatures. Recent work has investigated the role of variation in Ldh-B expression. There are differences in the levels of Ldh-B protein, mRNA, and transcription rate. We have addressed the mechanisms responsible for differences in transcription rate by a combination of sequence comparison, DNase I footprinting, and functional analyses both in vitro and in vivo. We have shown that variation in the regulatory sequence of Ldh-B is responsible for the differences in transcription rate between populations and that the patterns of variation are inconsistent with a neutral model of molecular evolution. This functional differentiation, coupled with departures from neutral expectations, suggests that natural selection has acted on the regulation of Ldh-B. This article illustrates the value of a multidisciplinary approach in addressing problems in gene structure, expression, and evolutionary adaptation.",
    url = "https://doi.org/10.1002/(sici)1097-010x(199809/10)282:1/2<71::aid-jez11>3.0.co;2-j",
    doi = "10.1002/(sici)1097-010x(199809/10)282:1/2<71::aid-jez11>3.0.co;2-j",
    openalex = "W1982599952",
    references = "brown1988biochemical, cashon1981biochemical, doi1010160092867489901761, doi101017cbo9780511693281002, doi101038351652a0, doi101093genetics1161153, doi101111j155856461975tb00851x, doi101111j155856461986tb05740x, doi101126science1690918, doi101126science2678474, doi101146annureves26110195002155, doi101146annurevge25120191003213"
}

In many marine species, high levels of gene flow ensure that the genetic signal from population differentiation is weak. As a consequence, various errors associated with estimating population genetic parameters that might normally be safely ignored assume a relatively greater importance. This fact has important implications for the use of genetic data to address two common questions in fishery conservation and management: (1) How many stocks of a given species are there? and (2) How much gene flow occurs among stocks? This article discusses strategies to maximize the signal:noise ratio in genetic studies of marine species and suggests a quantitative method to correct for bias due to a common sampling problem. For many marine species, however, genetic methods alone cannot fully resolve these key management questions because the amount of migration necessary to eliminate most genetic evidence of stock structure (only a handful of individuals per generation) will generally be inconsequential as a force for rebuilding depleted populations on a time scale of interest to humans. These limitations emphasize the importance of understanding the biology and life history of the target species-first, to guide design of the sampling program, and second, so that additional information can be used to supplement indirect estimates of migration rates based on genetic data.

@article{doi101093jhered895438,
    author = "Waples, Robin S.",
    title = "Separating the wheat from the chaff: patterns of genetic differentiation in high gene flow species",
    year = "1998",
    journal = "Journal of Heredity",
    abstract = "In many marine species, high levels of gene flow ensure that the genetic signal from population differentiation is weak. As a consequence, various errors associated with estimating population genetic parameters that might normally be safely ignored assume a relatively greater importance. This fact has important implications for the use of genetic data to address two common questions in fishery conservation and management: (1) How many stocks of a given species are there? and (2) How much gene flow occurs among stocks? This article discusses strategies to maximize the signal:noise ratio in genetic studies of marine species and suggests a quantitative method to correct for bias due to a common sampling problem. For many marine species, however, genetic methods alone cannot fully resolve these key management questions because the amount of migration necessary to eliminate most genetic evidence of stock structure (only a handful of individuals per generation) will generally be inconsequential as a force for rebuilding depleted populations on a time scale of interest to humans. These limitations emphasize the importance of understanding the biology and life history of the target species-first, to guide design of the sampling program, and second, so that additional information can be used to supplement indirect estimates of migration rates based on genetic data.",
    url = "https://doi.org/10.1093/jhered/89.5.438",
    doi = "10.1093/jhered/89.5.438",
    openalex = "W2098787755",
    references = "doi101146annureves16110185002141"
}

Adaptation to contaminants in the environment has been studied extensively in microbes, insects, and plants, and increasing evidence suggests that certain vertebrate populations as well are evolving in response to pollution. Here, we show that F1 and F2 laboratory-raised offspring of killifish (Fundulus heteroclitus, also known as mummichog) from a highly contaminated site on the Elizabeth River (Virginia, USA) are more resistant to the toxicity of Elizabeth River sediments than are offspring of reference site killifish. This resistance is more marked in the F1 than in the F2 generation, but it remains significant in the F2 generation, indicating that the resistant phenotype in the feral Elizabeth River killifish is based on both genetic and nongenetic mechanisms. In addition, both the F1 and F2 generation offspring of the Elizabeth River killifish are more susceptible to other stressors, both anthropogenic (photoenhanced toxicity) and natural (hypoxia), suggesting that the changes that have conferred resistance to the toxicity of the Elizabeth River sediments carry a cost of reduced fitness in other contexts. Corresponding Editor: J. E. McDowell.

@article{doi1018901051076120030130490haafci20co2,
    author = "Meyer, Joel N. and Giulio, Richard T. Di",
    title = "HERITABLE ADAPTATION AND FITNESS COSTS IN KILLIFISH (FUNDULUS HETEROCLITUS) INHABITING A POLLUTED ESTUARY",
    year = "2003",
    journal = "Ecological Applications",
    abstract = "Adaptation to contaminants in the environment has been studied extensively in microbes, insects, and plants, and increasing evidence suggests that certain vertebrate populations as well are evolving in response to pollution. Here, we show that F1 and F2 laboratory-raised offspring of killifish (Fundulus heteroclitus, also known as mummichog) from a highly contaminated site on the Elizabeth River (Virginia, USA) are more resistant to the toxicity of Elizabeth River sediments than are offspring of reference site killifish. This resistance is more marked in the F1 than in the F2 generation, but it remains significant in the F2 generation, indicating that the resistant phenotype in the feral Elizabeth River killifish is based on both genetic and nongenetic mechanisms. In addition, both the F1 and F2 generation offspring of the Elizabeth River killifish are more susceptible to other stressors, both anthropogenic (photoenhanced toxicity) and natural (hypoxia), suggesting that the changes that have conferred resistance to the toxicity of the Elizabeth River sediments carry a cost of reduced fitness in other contexts. Corresponding Editor: J. E. McDowell.",
    url = "https://doi.org/10.1890/1051-0761(2003)013[0490:haafci]2.0.co;2",
    doi = "10.1890/1051-0761(2003)013[0490:haafci]2.0.co;2",
    openalex = "W2147639663",
    references = "doi101007s002270050520"
}

Maintenance of ion balance requires that ionoregulatory epithelia modulate ion flux in response to internal or environmental osmotic challenges. We have explored the basis of this functional plasticity in the gills of the euryhaline killifish Fundulus heteroclitus. The expression patterns of several genes encoding ion transport proteins were quantified after transfer from near-isosmotic brackish water [10 parts/thousand (ppt)] to either freshwater (FW) or seawater (SW). Many changes in response to SW transfer were transient. Increased mRNA expression occurred 1 day after transfer for Na(+)-K(+)-ATPase-alpha(1a) (3-fold), Na(+)-K(+)-2Cl(-)-cotransporter 1 (NKCC1) (3-fold), and glucocorticoid receptor (1.3-fold) and was paralleled by elevated Na(+)-K(+)-ATPase activity (2-fold). The transient increase in NKCC1 mRNA expression was followed by a later 2-fold rise in NKCC protein abundance. In contrast to the other genes studied in the present work, mRNA expression of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel generally remained elevated (2-fold) in SW. No change in protein abundance was detected, however, suggesting posttranscriptional regulation. The responses to FW transfer were quite different from those to SW transfer. In particular, FW transfer increased Na(+)-K(+)-ATPase-alpha(1a) mRNA expression and Na(+)-K(+)-ATPase activity to a greater extent than did SW transfer but had no effect on V-type H(+)-ATPase expression, supporting the current suggestion that killifish gills transport Na(+) via Na(+)/H(+) exchange. These findings demonstrate unique patterns of ion transporter expression in killifish gills after salinity transfer and illustrate important mechanisms of functional plasticity in ion-transporting epithelia.

@article{doi101152ajpcell000542004,
    author = "Scott, Graham R. and Richards, Jeff G. and Forbush, Biff and Isenring, Paul and Schulte, Patricia M.",
    title = "Changes in gene expression in gills of the euryhaline killifish Fundulus heteroclitus after abrupt salinity transfer",
    year = "2004",
    journal = "American Journal of Physiology-Cell Physiology",
    abstract = "Maintenance of ion balance requires that ionoregulatory epithelia modulate ion flux in response to internal or environmental osmotic challenges. We have explored the basis of this functional plasticity in the gills of the euryhaline killifish Fundulus heteroclitus. The expression patterns of several genes encoding ion transport proteins were quantified after transfer from near-isosmotic brackish water [10 parts/thousand (ppt)] to either freshwater (FW) or seawater (SW). Many changes in response to SW transfer were transient. Increased mRNA expression occurred 1 day after transfer for Na(+)-K(+)-ATPase-alpha(1a) (3-fold), Na(+)-K(+)-2Cl(-)-cotransporter 1 (NKCC1) (3-fold), and glucocorticoid receptor (1.3-fold) and was paralleled by elevated Na(+)-K(+)-ATPase activity (2-fold). The transient increase in NKCC1 mRNA expression was followed by a later 2-fold rise in NKCC protein abundance. In contrast to the other genes studied in the present work, mRNA expression of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel generally remained elevated (2-fold) in SW. No change in protein abundance was detected, however, suggesting posttranscriptional regulation. The responses to FW transfer were quite different from those to SW transfer. In particular, FW transfer increased Na(+)-K(+)-ATPase-alpha(1a) mRNA expression and Na(+)-K(+)-ATPase activity to a greater extent than did SW transfer but had no effect on V-type H(+)-ATPase expression, supporting the current suggestion that killifish gills transport Na(+) via Na(+)/H(+) exchange. These findings demonstrate unique patterns of ion transporter expression in killifish gills after salinity transfer and illustrate important mechanisms of functional plasticity in ion-transporting epithelia.",
    url = "https://doi.org/10.1152/ajpcell.00054.2004",
    doi = "10.1152/ajpcell.00054.2004",
    openalex = "W2058526501",
    references = "doi1023071442526"
}

Variation among populations in gene expression should be related to the accumulation of random-neutral changes and evolution by natural selection. The following evolutionary analysis has general applicability to biological and medical science because it accounts for genetic relatedness and identifies patterns of expression variation that are affected by natural selection. To identify genes evolving by natural selection, we allocate the maximum among-population variation to genetic distance and then examine the remaining variation relative to a hypothesized important ecological parameter (temperature). These analyses measure the expression of metabolic genes in common-gardened populations of the fish Fundulus heteroclitus whose habitat is distributed along a steep thermal gradient. Although much of the variation in gene expression fits a null model of neutral drift, the variation in expression for 22% of the genes that regress with habitat temperature was far greater than could be accounted for by genetic distance alone. The most parsimonious explanation for among-population variation for these genes is evolution by natural selection. In addition, many metabolic genes have patterns of variation incongruent with neutral evolution: They have too much or too little variation. These patterns of biological variation in expression may reflect important physiological or ecological functions.

@article{doi101073pnas0507648103,
    author = "Whitehead, Andrew and Crawford, D. L.",
    title = "Neutral and adaptive variation in gene expression",
    year = "2006",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = "Variation among populations in gene expression should be related to the accumulation of random-neutral changes and evolution by natural selection. The following evolutionary analysis has general applicability to biological and medical science because it accounts for genetic relatedness and identifies patterns of expression variation that are affected by natural selection. To identify genes evolving by natural selection, we allocate the maximum among-population variation to genetic distance and then examine the remaining variation relative to a hypothesized important ecological parameter (temperature). These analyses measure the expression of metabolic genes in common-gardened populations of the fish Fundulus heteroclitus whose habitat is distributed along a steep thermal gradient. Although much of the variation in gene expression fits a null model of neutral drift, the variation in expression for 22\% of the genes that regress with habitat temperature was far greater than could be accounted for by genetic distance alone. The most parsimonious explanation for among-population variation for these genes is evolution by natural selection. In addition, many metabolic genes have patterns of variation incongruent with neutral evolution: They have too much or too little variation. These patterns of biological variation in expression may reflect important physiological or ecological functions.",
    url = "https://doi.org/10.1073/pnas.0507648103",
    doi = "10.1073/pnas.0507648103",
    openalex = "W2171931257",
    references = "cashon1981biochemical, doi101038ng1201365, doi101073pnas1530509100, doi101073pnas86239365, doi101086284325, doi101093oso97801985464120010001, doi101093sysbio41118, doi101111j001438202003tb00285x, doi101111j1365294x200602859x, doi101111j155856461967tb03411x, doi101126science1090005, doi105860choice295104, openalexw2080618944"
}

Knowledge of geographic and temporal scales of adaptive genetic variation is crucial to species conservation, yet understanding of these phenomena, particularly in marine systems, is scant. Until recently, the belief has been that because most marine species have highly dispersive or mobile life stages, local adaptation could occur only on broad geographic scales. This view is supported by comparatively low levels of genetic variation among populations as detected by neutral markers. Similarly, the time scale of adaptive divergence has also been assumed to be very long, requiring thousands of generations. Recent studies of a variety of species have challenged these beliefs. First, there is strong evidence of geographically structured local adaptation in physiological and morphological traits. Second, the proportion of quantitative trait variation at the among‐population level (Q ST) is much higher than it is for neutral markers (F ST) and these two metrics of genetic variation are poorly correlated. Third, evidence that selection is a potent evolutionary force capable of sustaining adaptive divergence on contemporary time scales is summarized. The differing spatial and temporal scales of adaptive v. neutral genetic divergence call for a new paradigm in thinking about the relationship between phenogeography (the geography of phenotypic variation) and phylogeography (the geography of lineages) in marine species. The idea that contemporary selective processes can cause fine‐scale spatial and temporal divergence underscores the need for a new emphasis on Darwinian fishery science.

@article{doi101111j10958649200601274x,
    author = "Conover, David O. and Clarke, Lora M. and Munch, Stephan B. and Wagner, Gunar",
    title = "Spatial and temporal scales of adaptive divergence in marine fishes and the implications for conservation",
    year = "2006",
    journal = "Journal of Fish Biology",
    abstract = "Knowledge of geographic and temporal scales of adaptive genetic variation is crucial to species conservation, yet understanding of these phenomena, particularly in marine systems, is scant. Until recently, the belief has been that because most marine species have highly dispersive or mobile life stages, local adaptation could occur only on broad geographic scales. This view is supported by comparatively low levels of genetic variation among populations as detected by neutral markers. Similarly, the time scale of adaptive divergence has also been assumed to be very long, requiring thousands of generations. Recent studies of a variety of species have challenged these beliefs. First, there is strong evidence of geographically structured local adaptation in physiological and morphological traits. Second, the proportion of quantitative trait variation at the among‐population level (Q ST) is much higher than it is for neutral markers (F ST) and these two metrics of genetic variation are poorly correlated. Third, evidence that selection is a potent evolutionary force capable of sustaining adaptive divergence on contemporary time scales is summarized. The differing spatial and temporal scales of adaptive v. neutral genetic divergence call for a new paradigm in thinking about the relationship between phenogeography (the geography of phenotypic variation) and phylogeography (the geography of lineages) in marine species. The idea that contemporary selective processes can cause fine‐scale spatial and temporal divergence underscores the need for a new emphasis on Darwinian fishery science.",
    url = "https://doi.org/10.1111/j.1095-8649.2006.01274.x",
    doi = "10.1111/j.1095-8649.2006.01274.x",
    openalex = "W2157229536",
    references = "doi101002sici1097010x199809102821271aidjez1130co2j, doi101071mf03023, doi1023072390285"
}

The mummichog, Fundulus heteroclitus, exhibits extensive latitudinal clinal variation in a number of physiological and biochemical traits, coupled with phylogeographical patterns at mitochondrial and nuclear DNA loci that suggest a complicated history of spatially variable selection and secondary intergradation. This species continues to serve as a model for understanding local and regional adaptation to variable environments. Resolving the influences of historical processes on the distribution of genetic variation within and among extant populations of F. heteroclitus is crucial to a better understanding of how populations evolve in the context of contemporary environments. In this study, we analysed geographical patterns of genetic variation at eight microsatellite loci among 15 populations of F. heteroclitus distributed throughout the North American range of the species from Nova Scotia to Georgia. Genetic variation in Northern populations was lower than in Southern populations and was strongly correlated with latitude throughout the species range. The most common Northern alleles at all eight loci exhibited concordant latitudinal clinal patterns, and the existence of an abrupt transition zone in allele frequencies between Northern and Southern populations was similar to that observed for mitochondrial DNA and allozyme loci. A significant pattern of isolation by distance was observed both within and between northern and southern regions. This pattern was unexpected, particularly for northern populations, given the recent colonization history of post-Pleistocene habitats, and was inconsistent with either a recent northward population expansion or a geographically restricted northern Pleistocene refugium. The data provided no evidence for recent population bottlenecks, and estimates of historical effective population sizes suggest that post-Pleistocene populations have been large throughout the species distribution. These results suggest that F. heteroclitus was broadly distributed throughout most of its current range during the last glacial event and that the abrupt transition in allele frequencies that separate Northern and Southern populations may reflect regional disequilibrium conditions associated with the post-Pleistocene colonization history of habitats in that region.

@article{doi101111j1365294x200602859x,
    author = "Adams, Stephanie M. and LINDMEIER, JAMES B. and Duvernell, David D.",
    title = "Microsatellite analysis of the phylogeography, Pleistocene history and secondary contact hypotheses for the killifish, Fundulus heteroclitus",
    year = "2006",
    journal = "Molecular Ecology",
    abstract = "The mummichog, Fundulus heteroclitus, exhibits extensive latitudinal clinal variation in a number of physiological and biochemical traits, coupled with phylogeographical patterns at mitochondrial and nuclear DNA loci that suggest a complicated history of spatially variable selection and secondary intergradation. This species continues to serve as a model for understanding local and regional adaptation to variable environments. Resolving the influences of historical processes on the distribution of genetic variation within and among extant populations of F. heteroclitus is crucial to a better understanding of how populations evolve in the context of contemporary environments. In this study, we analysed geographical patterns of genetic variation at eight microsatellite loci among 15 populations of F. heteroclitus distributed throughout the North American range of the species from Nova Scotia to Georgia. Genetic variation in Northern populations was lower than in Southern populations and was strongly correlated with latitude throughout the species range. The most common Northern alleles at all eight loci exhibited concordant latitudinal clinal patterns, and the existence of an abrupt transition zone in allele frequencies between Northern and Southern populations was similar to that observed for mitochondrial DNA and allozyme loci. A significant pattern of isolation by distance was observed both within and between northern and southern regions. This pattern was unexpected, particularly for northern populations, given the recent colonization history of post-Pleistocene habitats, and was inconsistent with either a recent northward population expansion or a geographically restricted northern Pleistocene refugium. The data provided no evidence for recent population bottlenecks, and estimates of historical effective population sizes suggest that post-Pleistocene populations have been large throughout the species distribution. These results suggest that F. heteroclitus was broadly distributed throughout most of its current range during the last glacial event and that the abrupt transition in allele frequencies that separate Northern and Southern populations may reflect regional disequilibrium conditions associated with the post-Pleistocene colonization history of habitats in that region.",
    url = "https://doi.org/10.1111/j.1365-294x.2006.02859.x",
    doi = "10.1111/j.1365-294x.2006.02859.x",
    openalex = "W2140008960",
    references = "cashon1981biochemical, doi101007bf02300753, doi10103835016000, doi101093genetics1312479, doi101093genetics1391457, doi101093genetics14442001, doi101093genetics1552945, doi101111j1365294x200402396x, doi101111j146918091949tb02451x, doi101111j155856461984tb05657x, doi101146annureves16110185000553, whitmore1967elephant"
}

Populations of common killifish, Fundulus heteroclitus, are distributed along the Atlantic coast of North America through a steep latitudinal thermal gradient. We examined intraspecific variation in whole-animal thermal tolerance and its relationship to the heat shock response in killifish from the northern and southern extremes of the species range. Critical thermal maxima were significantly higher in southern than in northern fish by approximately 1.5 degrees C at a wide range of acclimation temperatures (from 2-34 degrees C), and critical thermal minima differed by approximately 1.5 degrees C at acclimation temperatures above 22 degrees C, converging on the freezing point of brackish water at lower acclimation temperatures. To determine whether these differences in whole-organism thermal tolerance were reflected in differences in either the sequence or regulation of the heat shock protein genes (hsps) we obtained complete cDNA sequences for hsc70, hsp70-1 and hsp70-2, and partial sequences of hsp90alpha and hsp90beta. There were no fixed differences in amino acid sequence between populations in either hsp70-1 or hsp70-2, and only a single conservative substitution between populations in hsc70. By contrast, there were significant differences between populations in the expression of many, but not all, of these genes. Both northern and southern killifish significantly increased hsp70-2 levels above control values (T(on)) at a heat shock temperature of 33 degrees C, but the magnitude of this induction was greater in northern fish, suggesting that northern fish may be more susceptible to thermal damage than are southern fish. In contrast, hsp70-1 mRNA levels increased gradually and to the same extent in response to heat shock in both populations. Hsc70 mRNA levels were significantly elevated by heat shock in southern fish, but not in northern fish. Similarly, the more thermotolerant southern killifish had a T(on) for hsp90alpha of 30 degrees C, 2 degrees C lower than that of northern fish. This observation combined with the ability of southern killifish to upregulate hsc70 in response to heat shock suggests a possible role for these hsps in whole-organism differences in thermal tolerance. These data highlight the importance of considering the complexity of the heat shock response across multiple isoforms when attempting to make linkages to whole-organism traits such as thermal tolerance.

@article{doi101242jeb02260,
    author = "Fangue, Nann A. and Hofmeister, Myriam and Schulte, Patricia M.",
    title = "Intraspecific variation in thermal tolerance and heat shock protein gene expression in common killifish, Fundulus heteroclitus",
    year = "2006",
    journal = "Journal of Experimental Biology",
    abstract = "Populations of common killifish, Fundulus heteroclitus, are distributed along the Atlantic coast of North America through a steep latitudinal thermal gradient. We examined intraspecific variation in whole-animal thermal tolerance and its relationship to the heat shock response in killifish from the northern and southern extremes of the species range. Critical thermal maxima were significantly higher in southern than in northern fish by approximately 1.5 degrees C at a wide range of acclimation temperatures (from 2-34 degrees C), and critical thermal minima differed by approximately 1.5 degrees C at acclimation temperatures above 22 degrees C, converging on the freezing point of brackish water at lower acclimation temperatures. To determine whether these differences in whole-organism thermal tolerance were reflected in differences in either the sequence or regulation of the heat shock protein genes (hsps) we obtained complete cDNA sequences for hsc70, hsp70-1 and hsp70-2, and partial sequences of hsp90alpha and hsp90beta. There were no fixed differences in amino acid sequence between populations in either hsp70-1 or hsp70-2, and only a single conservative substitution between populations in hsc70. By contrast, there were significant differences between populations in the expression of many, but not all, of these genes. Both northern and southern killifish significantly increased hsp70-2 levels above control values (T(on)) at a heat shock temperature of 33 degrees C, but the magnitude of this induction was greater in northern fish, suggesting that northern fish may be more susceptible to thermal damage than are southern fish. In contrast, hsp70-1 mRNA levels increased gradually and to the same extent in response to heat shock in both populations. Hsc70 mRNA levels were significantly elevated by heat shock in southern fish, but not in northern fish. Similarly, the more thermotolerant southern killifish had a T(on) for hsp90alpha of 30 degrees C, 2 degrees C lower than that of northern fish. This observation combined with the ability of southern killifish to upregulate hsc70 in response to heat shock suggests a possible role for these hsps in whole-organism differences in thermal tolerance. These data highlight the importance of considering the complexity of the heat shock response across multiple isoforms when attempting to make linkages to whole-organism traits such as thermal tolerance.",
    url = "https://doi.org/10.1242/jeb.02260",
    doi = "10.1242/jeb.02260",
    openalex = "W2153013358",
    references = "doi101002sici1097010x199809102821271aidjez1130co2j"
}

A number of evolutionary mechanisms have been suggested for generating low but significant genetic structuring among marine fish populations. We used nine microsatellite loci and recently developed methods in landscape genetics and coalescence-based estimation of historical gene flow and effective population sizes to assess temporal and spatial dynamics of the population structure in European flounder (Platichthys flesus L.). We collected 1062 flounders from 13 localities in the northeast Atlantic and Baltic Seas and found temporally stable and highly significant genetic differentiation among samples covering a large part of the species' range (global F(ST) = 0.024, P < 0.0001). In addition to historical processes, a number of contemporary acting evolutionary mechanisms were associated with genetic structuring. Physical forces, such as oceanographic and bathymetric barriers, were most likely related with the extreme isolation of the island population at the Faroe Islands. A sharp genetic break was associated with a change in life history from pelagic to benthic spawners in the Baltic Sea. Partial Mantel tests showed that geographical distance per se was not related with genetic structuring among Atlantic and western Baltic Sea samples. Alternative factors, such as dispersal potential and/or environmental gradients, could be important for generating genetic divergence in this region. The results show that the magnitude and scale of structuring generated by a specific mechanism depend critically on its interplay with other evolutionary mechanisms, highlighting the importance of investigating species with wide geographical and ecological distributions to increase our understanding of evolution in the marine environment.

@article{doi101111j1365294x200703367x,
    author = "Hemmer‐Hansen, Jakob and Nielsen, Einar Eg and Grønkjær, Peter and Loeschcke, Volker",
    title = "Evolutionary mechanisms shaping the genetic population structure of marine fishes; lessons from the European flounder (Platichthys flesus L.)",
    year = "2007",
    journal = "Molecular Ecology",
    abstract = "A number of evolutionary mechanisms have been suggested for generating low but significant genetic structuring among marine fish populations. We used nine microsatellite loci and recently developed methods in landscape genetics and coalescence-based estimation of historical gene flow and effective population sizes to assess temporal and spatial dynamics of the population structure in European flounder (Platichthys flesus L.). We collected 1062 flounders from 13 localities in the northeast Atlantic and Baltic Seas and found temporally stable and highly significant genetic differentiation among samples covering a large part of the species' range (global F(ST) = 0.024, P < 0.0001). In addition to historical processes, a number of contemporary acting evolutionary mechanisms were associated with genetic structuring. Physical forces, such as oceanographic and bathymetric barriers, were most likely related with the extreme isolation of the island population at the Faroe Islands. A sharp genetic break was associated with a change in life history from pelagic to benthic spawners in the Baltic Sea. Partial Mantel tests showed that geographical distance per se was not related with genetic structuring among Atlantic and western Baltic Sea samples. Alternative factors, such as dispersal potential and/or environmental gradients, could be important for generating genetic divergence in this region. The results show that the magnitude and scale of structuring generated by a specific mechanism depend critically on its interplay with other evolutionary mechanisms, highlighting the importance of investigating species with wide geographical and ecological distributions to increase our understanding of evolution in the marine environment.",
    url = "https://doi.org/10.1111/j.1365-294x.2007.03367.x",
    doi = "10.1111/j.1365-294x.2007.03367.x",
    openalex = "W2120255171",
    references = "doi101111j1365294x200602859x"
}

Genetic admixture of distinct gene pools is the consequence of complex spatiotemporal processes that could have involved massive migration and local mating during the history of a species. However, current methods for estimating individual admixture proportions lack the incorporation of such a piece of information. Here, we extend Bayesian clustering algorithms by including global trend surfaces and spatial autocorrelation in the prior distribution on individual admixture coefficients. We test our algorithm by using spatially explicit and realistic coalescent simulations of colonization followed by secondary contact. By coupling our multiscale spatial analyses with a Bayesian evaluation of model complexity and fit, we show that the algorithm provides a correct description of smooth clinal variation, while still detecting zones of sharp variation when they are present in the data. We also apply our approach to understand the population structure of the killifish, Fundulus heteroclitus, for which the algorithm uncovers a presumed contact zone in the Atlantic coast of North America.

@article{doi101093molbevmsp106,
    author = "Durand, Éric and Jay, Frédéric and Gaggiotti, Oscar E. and François, Olivier",
    title = "Spatial Inference of Admixture Proportions and Secondary Contact Zones",
    year = "2009",
    journal = "Molecular Biology and Evolution",
    abstract = "Genetic admixture of distinct gene pools is the consequence of complex spatiotemporal processes that could have involved massive migration and local mating during the history of a species. However, current methods for estimating individual admixture proportions lack the incorporation of such a piece of information. Here, we extend Bayesian clustering algorithms by including global trend surfaces and spatial autocorrelation in the prior distribution on individual admixture coefficients. We test our algorithm by using spatially explicit and realistic coalescent simulations of colonization followed by secondary contact. By coupling our multiscale spatial analyses with a Bayesian evaluation of model complexity and fit, we show that the algorithm provides a correct description of smooth clinal variation, while still detecting zones of sharp variation when they are present in the data. We also apply our approach to understand the population structure of the killifish, Fundulus heteroclitus, for which the algorithm uncovers a presumed contact zone in the Atlantic coast of North America.",
    url = "https://doi.org/10.1093/molbev/msp106",
    doi = "10.1093/molbev/msp106",
    openalex = "W2106728534",
    references = "doi101111j1365294x200602859x, doi101146annurevge25120191003213"
}

Although range expansions have occurred recurrently in the history of most species, their genetic consequences have been little investigated. Theoretical studies show that range expansions are quite different from pure demographic expansions and that the extent of recent gene flow conditions expected patterns of molecular diversity within and between populations. Spatially explicit simulation studies have led to unexpected and fascinating results about genetic patterns emerging after a range expansion. For instance, spatial expansions can generate allele frequency gradients, promote the surfing of rare variants into newly occupied territories, induce the structuring of newly colonized areas into distinct sectors of low genetic diversity, or lead to massive introgression of local genes into the genome of an invading species. Interestingly, most of these patterns had been previously attributed to distinct selective processes, showing that taking into account the dynamic nature of a species range can lead to a paradigm shift in our perception of evolutionary processes.

@article{doi101146annurevecolsys39110707173414,
    author = "Excoffier, Laurent and Foll, Matthieu and Petit, Rémy J.",
    title = "Genetic Consequences of Range Expansions",
    year = "2009",
    journal = "Annual Review of Ecology Evolution and Systematics",
    abstract = "Although range expansions have occurred recurrently in the history of most species, their genetic consequences have been little investigated. Theoretical studies show that range expansions are quite different from pure demographic expansions and that the extent of recent gene flow conditions expected patterns of molecular diversity within and between populations. Spatially explicit simulation studies have led to unexpected and fascinating results about genetic patterns emerging after a range expansion. For instance, spatial expansions can generate allele frequency gradients, promote the surfing of rare variants into newly occupied territories, induce the structuring of newly colonized areas into distinct sectors of low genetic diversity, or lead to massive introgression of local genes into the genome of an invading species. Interestingly, most of these patterns had been previously attributed to distinct selective processes, showing that taking into account the dynamic nature of a species range can lead to a paradigm shift in our perception of evolutionary processes.",
    url = "https://doi.org/10.1146/annurev.ecolsys.39.110707.173414",
    doi = "10.1146/annurev.ecolsys.39.110707.173414",
    openalex = "W2113401798",
    references = "doi10103835016000, doi101093genetics1472915, doi101111j146918091937tb02153x, doi101146annurevecolsys39110707173430, doi101146annureves16110185000553"
}

The limits of species ranges can be determined by a number of biotic and abiotic interactions, and in areas where closely related species overlap, some degree of reproductive isolation must exist in order for them to remain distinct. Understanding these interactions is essential for understanding what limits species distributions or causes hybridization. Fundulus heteroclitus (Mummichog) and Fundulus grandis (Gulf Killifish) are two closely related species with similar morphologies and ecological niches. Both species have widespread distributions that overlap in northeastern Florida. In the present study, two highly divergent loci (one nuclear and one mitochondrial) were utilized to distinguish these fundulid species in order to identify their ranges and to detect hybrids. Analysis of specimens collected along a north to south gradient in northeastern Florida salt marshes established that a relatively sharp transition (≈38 km) from relatively pure Mummichog populations to relatively pure F. grandis populations existed south of Jacksonville, FL, centered near Flagler Beach, FL. Putative hybrid genotypes were detected at moderate frequencies within the contact zone, suggesting that successful hybridization is likely occurring between the two species, but is relatively uncommon. These results provide a stepping stone to investigate the types of reproductive barriers that are involved in maintaining species distinctions in this system and their effects on the species' ranges and ecological interactions.

@article{doi1016560580080203,
    author = "Gonzalez, Iara and Levin, Michael and Jermanus, Sura and Watson, Brent and Gilg, Matthew R.",
    title = "Genetic Assessment of Species Ranges in Fundulus heteroclitus and F. grandis in Northeastern Florida Salt Marshes",
    year = "2009",
    journal = "Southeastern Naturalist",
    abstract = "The limits of species ranges can be determined by a number of biotic and abiotic interactions, and in areas where closely related species overlap, some degree of reproductive isolation must exist in order for them to remain distinct. Understanding these interactions is essential for understanding what limits species distributions or causes hybridization. Fundulus heteroclitus (Mummichog) and Fundulus grandis (Gulf Killifish) are two closely related species with similar morphologies and ecological niches. Both species have widespread distributions that overlap in northeastern Florida. In the present study, two highly divergent loci (one nuclear and one mitochondrial) were utilized to distinguish these fundulid species in order to identify their ranges and to detect hybrids. Analysis of specimens collected along a north to south gradient in northeastern Florida salt marshes established that a relatively sharp transition (≈38 km) from relatively pure Mummichog populations to relatively pure F. grandis populations existed south of Jacksonville, FL, centered near Flagler Beach, FL. Putative hybrid genotypes were detected at moderate frequencies within the contact zone, suggesting that successful hybridization is likely occurring between the two species, but is relatively uncommon. These results provide a stepping stone to investigate the types of reproductive barriers that are involved in maintaining species distinctions in this system and their effects on the species' ranges and ecological interactions.",
    url = "https://doi.org/10.1656/058.008.0203",
    doi = "10.1656/058.008.0203",
    openalex = "W2079968376",
    references = "duggins1989biochemical"
}

A major challenges facing landscape geneticists studying adaptive variation is to include all the environmental variables that might be correlated with allele frequencies across the genome. One way of identifying loci that are possibly under selection is to see which ones are associated with environmental gradient or heterogeneity. Since it is difficult to measure all environmental variables, one may take advantage of the spatial nature of environmental filters to incorporate the effect of unaccounted environmental variables in the analysis. Assuming that the spatial signature of these variables is broad-scaled, broad-scale Moran's eigenvector maps (MEM) can be included as explanatory variables in the analysis as proxies for unmeasured environmental variables. We applied this approach to two data sets of the alpine plant Arabis alpina. The first consisted of 140 AFLP loci sampled at 130 sites across the European Alps (large scale). The second one consisted of 712 AFLP loci sampled at 93 sites (regional scale) in three mountain massifs (local scale) of the French Alps. For each scale, we regressed the frequencies of each AFLP allele on a set of eco-climatic and MEM variables as predictors. Twelve (large scale) and 11% (regional scale) of all loci were detected as significantly correlated to at least one of the predictors (> 0.5), and, except for one massif, 17% at the local scale. After accounting for spatial effects, temperature and precipitation were the two major determinants of allele distributions. Our study shows how MEM models can account for unmeasured environmental variation in landscape genetics models.

@article{doi101111j1365294x201004716x,
    author = "Manel, Stéphanie and Poncet, Bénédicte and Legendre, Pierre and Gugerli, Félix and Holderegger, Rolf",
    title = "Common factors drive adaptive genetic variation at different spatial scales in Arabis alpina",
    year = "2010",
    journal = "Molecular Ecology",
    abstract = "A major challenges facing landscape geneticists studying adaptive variation is to include all the environmental variables that might be correlated with allele frequencies across the genome. One way of identifying loci that are possibly under selection is to see which ones are associated with environmental gradient or heterogeneity. Since it is difficult to measure all environmental variables, one may take advantage of the spatial nature of environmental filters to incorporate the effect of unaccounted environmental variables in the analysis. Assuming that the spatial signature of these variables is broad-scaled, broad-scale Moran's eigenvector maps (MEM) can be included as explanatory variables in the analysis as proxies for unmeasured environmental variables. We applied this approach to two data sets of the alpine plant Arabis alpina. The first consisted of 140 AFLP loci sampled at 130 sites across the European Alps (large scale). The second one consisted of 712 AFLP loci sampled at 93 sites (regional scale) in three mountain massifs (local scale) of the French Alps. For each scale, we regressed the frequencies of each AFLP allele on a set of eco-climatic and MEM variables as predictors. Twelve (large scale) and 11\% (regional scale) of all loci were detected as significantly correlated to at least one of the predictors (> 0.5), and, except for one massif, 17\% at the local scale. After accounting for spatial effects, temperature and precipitation were the two major determinants of allele distributions. Our study shows how MEM models can account for unmeasured environmental variation in landscape genetics models.",
    url = "https://doi.org/10.1111/j.1365-294x.2010.04716.x",
    doi = "10.1111/j.1365-294x.2010.04716.x",
    openalex = "W2156951592",
    references = "doi1018900711621"
}

The physiological link between oxygen availability and mitochondrial function is well established. However, whether or not fitness variation is associated with mitochondrial genotypes in the field remains a contested topic in evolutionary biology. In this study, we draw on a population of the teleost fish, Fundulus heteroclitus, where functionally distinct subspecies hybridize, likely as a result of past glacial events. We had two specific aims: (i) to determine the effect of mtDNA genotype on survivorship of male and female fish under hypoxic stress and (ii) to determine the effect of hypoxic stress, sex and mtDNA genotype on gene expression. We found an unexpected and highly significant effect of sex on survivorship under hypoxic conditions, but no significant effect of mtDNA genotype. Gene expression analyses revealed hundreds of transcripts differentially regulated by sex and hypoxia. Mitochondrial transcripts and other predicted pathways were among those influenced by hypoxic stress, and a transcript corresponding to the mtDNA control region was the most highly suppressed transcript under the conditions of hypoxia. An RT-PCR experiment on the control region was consistent with microarray results. Effects of mtDNA sequence variation on genome expression were limited; however, a potentially important epistasis between mtDNA sequence and expression of a nuclear-encoded mitochondrial translation protein was discovered. Overall, these results confirm that mitochondrial regulation is a major component of hypoxia tolerance and further suggest that purifying selection has been the predominant selective force on mitochondrial genomes in these two subspecies.

@article{doi101111j1365294x201105290x,
    author = "Flight, Patrick A. and Nacci, Diane and Champlin, Denise and Whitehead, Andrew and Rand, David M.",
    title = "The effects of mitochondrial genotype on hypoxic survival and gene expression in a hybrid population of the killifish, Fundulus heteroclitus",
    year = "2011",
    journal = "Molecular Ecology",
    abstract = "The physiological link between oxygen availability and mitochondrial function is well established. However, whether or not fitness variation is associated with mitochondrial genotypes in the field remains a contested topic in evolutionary biology. In this study, we draw on a population of the teleost fish, Fundulus heteroclitus, where functionally distinct subspecies hybridize, likely as a result of past glacial events. We had two specific aims: (i) to determine the effect of mtDNA genotype on survivorship of male and female fish under hypoxic stress and (ii) to determine the effect of hypoxic stress, sex and mtDNA genotype on gene expression. We found an unexpected and highly significant effect of sex on survivorship under hypoxic conditions, but no significant effect of mtDNA genotype. Gene expression analyses revealed hundreds of transcripts differentially regulated by sex and hypoxia. Mitochondrial transcripts and other predicted pathways were among those influenced by hypoxic stress, and a transcript corresponding to the mtDNA control region was the most highly suppressed transcript under the conditions of hypoxia. An RT-PCR experiment on the control region was consistent with microarray results. Effects of mtDNA sequence variation on genome expression were limited; however, a potentially important epistasis between mtDNA sequence and expression of a nuclear-encoded mitochondrial translation protein was discovered. Overall, these results confirm that mitochondrial regulation is a major component of hypoxia tolerance and further suggest that purifying selection has been the predominant selective force on mitochondrial genomes in these two subspecies.",
    url = "https://doi.org/10.1111/j.1365-294x.2011.05290.x",
    doi = "10.1111/j.1365-294x.2011.05290.x",
    openalex = "W1902953741",
    references = "doi1010160003269790905984, doi101038nprot2008211, doi101093bioinformaticsbti551, doi101093bioinformaticsbtp187, doi101093molbevmsm092, doi1011111467986800346, doi101126science1156401, doi101146annureves16110185000553, doi101186gb200345p3, ropson1990biochemical"
}

The killifish Fundulus heteroclitus is abundant in osmotically dynamic estuaries and it can quickly adjust to extremes in environmental salinity. We performed a comparative osmotic challenge experiment to track the transcriptomic and physiological responses to two salinities throughout a time course of acclimation, and to explore the genome regulatory mechanisms that enable extreme osmotic acclimation. One southern and one northern coastal population, known to differ in their tolerance to hypo-osmotic exposure, were used as our comparative model. Both populations could maintain osmotic homeostasis when transferred from 32 to 0.4 p.p.t., but diverged in their compensatory abilities when challenged down to 0.1 p.p.t., in parallel with divergent transformation of gill morphology. Genes involved in cell volume regulation, nucleosome maintenance, ion transport, energetics, mitochondrion function, transcriptional regulation and apoptosis showed population- and salinity-dependent patterns of expression during acclimation. Network analysis confirmed the role of cytokine and kinase signaling pathways in coordinating the genome regulatory response to osmotic challenge, and also posited the importance of signaling coordinated through the transcription factor HNF-4α. These genome responses support hypotheses of which regulatory mechanisms are particularly relevant for enabling extreme physiological flexibility.

@article{doi101242jeb062075,
    author = "Whitehead, Andrew and Roach, Jennifer L. and Zhang, Shujun and Gálvez, Fernando",
    title = "Salinity- and population-dependent genome regulatory response during osmotic acclimation in the killifish (Fundulus heteroclitus) gill",
    year = "2012",
    journal = "Journal of Experimental Biology",
    abstract = "The killifish Fundulus heteroclitus is abundant in osmotically dynamic estuaries and it can quickly adjust to extremes in environmental salinity. We performed a comparative osmotic challenge experiment to track the transcriptomic and physiological responses to two salinities throughout a time course of acclimation, and to explore the genome regulatory mechanisms that enable extreme osmotic acclimation. One southern and one northern coastal population, known to differ in their tolerance to hypo-osmotic exposure, were used as our comparative model. Both populations could maintain osmotic homeostasis when transferred from 32 to 0.4 p.p.t., but diverged in their compensatory abilities when challenged down to 0.1 p.p.t., in parallel with divergent transformation of gill morphology. Genes involved in cell volume regulation, nucleosome maintenance, ion transport, energetics, mitochondrion function, transcriptional regulation and apoptosis showed population- and salinity-dependent patterns of expression during acclimation. Network analysis confirmed the role of cytokine and kinase signaling pathways in coordinating the genome regulatory response to osmotic challenge, and also posited the importance of signaling coordinated through the transcription factor HNF-4α. These genome responses support hypotheses of which regulatory mechanisms are particularly relevant for enabling extreme physiological flexibility.",
    url = "https://doi.org/10.1242/jeb.062075",
    doi = "10.1242/jeb.062075",
    openalex = "W2133306656",
    references = "doi101111j1365294x201105290x"
}

A common geographical pattern of genetic variation is the one-dimensional cline. Clines may be maintained by diversifying selection across a geographical gradient but can also reflect historical processes such as allopatry followed by secondary contact. To identify loci that may be undergoing diversifying selection, we examined the distribution of geographical variation patterns across the range of the killifish (Fundulus heteroclitus) in 310 loci, including microsatellites, allozymes, and single nucleotide polymorphisms. We employed two approaches to detect loci under strong diversifying selection. First, we developed an automated method to identify clinal variation on a per-locus basis and examined the distribution of clines to detect those that exhibited signifcantly steeper slopes. Second, we employed a classic [Formula: see text]-outlier method as a complementary approach. We also assessed performance of these techniques using simulations. Overall, latitudinal clines were detected in nearly half of all loci genotyped (i.e., all eight microsatellite loci, 12 of 16 allozyme loci and 44% of the 285 SNPs). With the exception of few outlier loci (notably mtDNA and malate dehydrogenase), the positions and slopes of Fundulus clines were statistically indistinguishable. The high frequency of latitudinal clines across the genome indicates that secondary contact plays a central role in the historical demography of this species. Our simulation results indicate that accurately detecting diversifying selection using genome scans is extremely difficult in species with a strong signal of secondary contact; neutral evolution under this history produces clines as steep as those expected under selection. Based on these results, we propose that demographic history can explain all clinal patterns observed in F. heteroclitus without invoking natural selection to either establish or maintain the pattern we observe today.

@article{doi101371journalpone0045138,
    author = "Strand, Allan E. and Williams, LM and Oleksiak, Marjorie F. and Sotka, Erik E.",
    title = "Can Diversifying Selection Be Distinguished from History in Geographic Clines? A Population Genomic Study of Killifish (Fundulus heteroclitus)",
    year = "2012",
    journal = "PLoS ONE",
    abstract = "A common geographical pattern of genetic variation is the one-dimensional cline. Clines may be maintained by diversifying selection across a geographical gradient but can also reflect historical processes such as allopatry followed by secondary contact. To identify loci that may be undergoing diversifying selection, we examined the distribution of geographical variation patterns across the range of the killifish (Fundulus heteroclitus) in 310 loci, including microsatellites, allozymes, and single nucleotide polymorphisms. We employed two approaches to detect loci under strong diversifying selection. First, we developed an automated method to identify clinal variation on a per-locus basis and examined the distribution of clines to detect those that exhibited signifcantly steeper slopes. Second, we employed a classic [Formula: see text]-outlier method as a complementary approach. We also assessed performance of these techniques using simulations. Overall, latitudinal clines were detected in nearly half of all loci genotyped (i.e., all eight microsatellite loci, 12 of 16 allozyme loci and 44\% of the 285 SNPs). With the exception of few outlier loci (notably mtDNA and malate dehydrogenase), the positions and slopes of Fundulus clines were statistically indistinguishable. The high frequency of latitudinal clines across the genome indicates that secondary contact plays a central role in the historical demography of this species. Our simulation results indicate that accurately detecting diversifying selection using genome scans is extremely difficult in species with a strong signal of secondary contact; neutral evolution under this history produces clines as steep as those expected under selection. Based on these results, we propose that demographic history can explain all clinal patterns observed in F. heteroclitus without invoking natural selection to either establish or maintain the pattern we observe today.",
    url = "https://doi.org/10.1371/journal.pone.0045138",
    doi = "10.1371/journal.pone.0045138",
    openalex = "W2005710170",
    references = "doi101046j1365294x200302063x, doi101093bioinformatics182337, doi101093oso97801950997440010001, doi101111j1365294x201105290x, doi101111j14718286200400828x, doi101111jbi14281, doi101146annureves16110185000553, doi101242jeb037473, doi1023073390, doi105860choice350883, openalexw1546828436, ropson1990biochemical"
}

Population genomic approaches are making rapid inroads in the study of non-model organisms, including marine taxa. To date, these marine studies have predominantly focused on rudimentary metrics describing the spatial and environmental context of their study region (e.g., geographical distance, average sea surface temperature, average salinity). We contend that a more nuanced and considered approach to quantifying seascape dynamics and patterns can strengthen population genomic investigations and help identify spatial, temporal, and environmental factors associated with differing selective regimes or demographic histories. Nevertheless, approaches for quantifying marine landscapes are complicated. Characteristic features of the marine environment, including pelagic living in flowing water (experienced by most marine taxa at some point in their life cycle), require a well-designed spatial-temporal sampling strategy and analysis. Many genetic summary statistics used to describe populations may be inappropriate for marine species with large population sizes, large species ranges, stochastic recruitment, and asymmetrical gene flow. Finally, statistical approaches for testing associations between seascapes and population genomic patterns are still maturing with no single approach able to capture all relevant considerations. None of these issues are completely unique to marine systems and therefore similar issues and solutions will be shared for many organisms regardless of habitat. Here, we outline goals and spatial approaches for landscape genomics with an emphasis on marine systems and review the growing empirical literature on seascape genomics. We review established tools and approaches and highlight promising new strategies to overcome select issues including a strategy to spatially optimize sampling. Despite the many challenges, we argue that marine systems may be especially well suited for identifying candidate genomic regions under environmentally mediated selection and that seascape genomic approaches are especially useful for identifying robust locus-by-environment associations.

@article{doi101093czzow067,
    author = "Riginos, Cynthia and Crandall, Eric D. and Liggins, Libby and Bongaerts, Pim and Treml, Eric A.",
    title = "Navigating the currents of seascape genomics: how spatial analyses can augment population genomic studies",
    year = "2016",
    journal = "Current Zoology",
    abstract = "Population genomic approaches are making rapid inroads in the study of non-model organisms, including marine taxa. To date, these marine studies have predominantly focused on rudimentary metrics describing the spatial and environmental context of their study region (e.g., geographical distance, average sea surface temperature, average salinity). We contend that a more nuanced and considered approach to quantifying seascape dynamics and patterns can strengthen population genomic investigations and help identify spatial, temporal, and environmental factors associated with differing selective regimes or demographic histories. Nevertheless, approaches for quantifying marine landscapes are complicated. Characteristic features of the marine environment, including pelagic living in flowing water (experienced by most marine taxa at some point in their life cycle), require a well-designed spatial-temporal sampling strategy and analysis. Many genetic summary statistics used to describe populations may be inappropriate for marine species with large population sizes, large species ranges, stochastic recruitment, and asymmetrical gene flow. Finally, statistical approaches for testing associations between seascapes and population genomic patterns are still maturing with no single approach able to capture all relevant considerations. None of these issues are completely unique to marine systems and therefore similar issues and solutions will be shared for many organisms regardless of habitat. Here, we outline goals and spatial approaches for landscape genomics with an emphasis on marine systems and review the growing empirical literature on seascape genomics. We review established tools and approaches and highlight promising new strategies to overcome select issues including a strategy to spatially optimize sampling. Despite the many challenges, we argue that marine systems may be especially well suited for identifying candidate genomic regions under environmentally mediated selection and that seascape genomic approaches are especially useful for identifying robust locus-by-environment associations.",
    url = "https://doi.org/10.1093/cz/zow067",
    doi = "10.1093/cz/zow067",
    openalex = "W2463608285",
    references = "doi101093czzow088, doi101111eva12288"
}

Highly fecund marine species with dispersive life-history stages often display large population sizes and wide geographic distribution ranges. Consequently, they are expected to experience reduced genetic drift, efficient selection fueled by frequent adaptive mutations, and high migration loads. This has important consequences for understanding how local adaptation proceeds in the sea. A key issue in this regard, relates to the genetic architecture underlying fitness traits. Theory predicts that adaptation may involve many genes but with a high variance in effect size. Therefore, the effect of selection on allele frequencies may be substantial for the largest effect size loci, but insignificant for small effect genes. In such a context, the performance of population genomic methods to unravel the genetic basis of adaptation depends on the fraction of adaptive genetic variance explained by the cumulative effect of outlier loci. Here, we address some methodological challenges associated with the detection of local adaptation using molecular approaches. We provide an overview of genome scan methods to detect selection, including those assuming complex demographic models that better describe spatial population structure. We then focus on quantitative genetics approaches that search for genotype-phenotype associations at different genomic scales, including genome-wide methods evaluating the cumulative effect of variants. We argue that the limited power of single locus tests can be alleviated by the use of polygenic scores to estimate the joint contribution of candidate variants to phenotypic variation.

@article{doi101093czzow088,
    author = "Gagnaire, Pierre‐Alexandre and Gaggiotti, Oscar E.",
    title = "Detecting polygenic selection in marine populations by combining population genomics and quantitative genetics approaches",
    year = "2016",
    journal = "Current Zoology",
    abstract = "Highly fecund marine species with dispersive life-history stages often display large population sizes and wide geographic distribution ranges. Consequently, they are expected to experience reduced genetic drift, efficient selection fueled by frequent adaptive mutations, and high migration loads. This has important consequences for understanding how local adaptation proceeds in the sea. A key issue in this regard, relates to the genetic architecture underlying fitness traits. Theory predicts that adaptation may involve many genes but with a high variance in effect size. Therefore, the effect of selection on allele frequencies may be substantial for the largest effect size loci, but insignificant for small effect genes. In such a context, the performance of population genomic methods to unravel the genetic basis of adaptation depends on the fraction of adaptive genetic variance explained by the cumulative effect of outlier loci. Here, we address some methodological challenges associated with the detection of local adaptation using molecular approaches. We provide an overview of genome scan methods to detect selection, including those assuming complex demographic models that better describe spatial population structure. We then focus on quantitative genetics approaches that search for genotype-phenotype associations at different genomic scales, including genome-wide methods evaluating the cumulative effect of variants. We argue that the limited power of single locus tests can be alleviated by the use of polygenic scores to estimate the joint contribution of candidate variants to phenotypic variation.",
    url = "https://doi.org/10.1093/cz/zow088",
    doi = "10.1093/cz/zow088",
    openalex = "W2518584709",
    references = "doi101007bf00484222, doi101038nature08185, doi101038nbt1486, doi101038ng608, doi101038ng686, doi101046j14390388200200356x, doi101073pnas0506580102, doi101093genetics1233585, doi101111j14610248200400684x, doi101111mec13360, doi101159000353879, doi1023072529912, powers1978biochemical"
}

Chaotic genetic patchiness (CGP) refers to surprising patterns of spatial and temporal genetic structure observed in some marine species at a scale where genetic variation should be efficiently homogenized by gene flow via larval dispersal. Here we review and discuss 4 mechanisms that could generate such unexpected patterns: selection, sweepstakes reproductive success, collective dispersal, and temporal shifts in local population dynamics. First, we review examples where genetic differentiation at specific loci was driven by diversifying selection, which was historically the first process invoked to explain CGP. Second, we turn to neutral demographic processes that may drive genome-wide effects, and whose effects on CGP may be enhanced when they act together. We discuss how sweepstakes reproductive success accelerates genetic drift and can thus generate genetic structure, provided that gene flow is not too strong. Collective dispersal is another mechanism whereby genetic structure can be maintained regardless of dispersal intensity, because it may prevent larval cohorts from becoming entirely mixed. Theoretical analyses of both the sweepstakes and the collective dispersal ideas are presented. Finally, we discuss an idea that has received less attention than the other ones just mentioned, namely temporal shifts in local population dynamics.

@article{doi101093czzow094,
    author = "Eldon, Bjarki and Riquet, Florentine and Yearsley, Jon M. and Jollivet, Didier and Broquet, Thomas",
    title = "Current hypotheses to explain genetic chaos under the sea",
    year = "2016",
    journal = "Current Zoology",
    abstract = "Chaotic genetic patchiness (CGP) refers to surprising patterns of spatial and temporal genetic structure observed in some marine species at a scale where genetic variation should be efficiently homogenized by gene flow via larval dispersal. Here we review and discuss 4 mechanisms that could generate such unexpected patterns: selection, sweepstakes reproductive success, collective dispersal, and temporal shifts in local population dynamics. First, we review examples where genetic differentiation at specific loci was driven by diversifying selection, which was historically the first process invoked to explain CGP. Second, we turn to neutral demographic processes that may drive genome-wide effects, and whose effects on CGP may be enhanced when they act together. We discuss how sweepstakes reproductive success accelerates genetic drift and can thus generate genetic structure, provided that gene flow is not too strong. Collective dispersal is another mechanism whereby genetic structure can be maintained regardless of dispersal intensity, because it may prevent larval cohorts from becoming entirely mixed. Theoretical analyses of both the sweepstakes and the collective dispersal ideas are presented. Finally, we discuss an idea that has received less attention than the other ones just mentioned, namely temporal shifts in local population dynamics.",
    url = "https://doi.org/10.1093/cz/zow094",
    doi = "10.1093/cz/zow094",
    openalex = "W2509367417",
    references = "doi101093czzow088"
}

The oxidative phosphorylation (OxPhos) pathway is responsible for most aerobic ATP production and is the only pathway with both nuclear and mitochondrial encoded proteins. The importance of the interactions between these two genomes has recently received more attention because of their potential evolutionary effects and how they may affect human health and disease. In many different organisms, healthy nuclear and mitochondrial genome hybrids between species or among distant populations within a species affect fitness and OxPhos functions. However, what is less understood is whether these interactions impact individuals within a single natural population. The significance of this impact depends on the strength of selection for mito-nuclear interactions. We examined whether mito-nuclear interactions alter allele frequencies for ~11,000 nuclear SNPs within a single, natural Fundulus heteroclitus population containing two divergent mitochondrial haplotypes (mt-haplotypes). Between the two mt-haplotypes, there are significant nuclear allele frequency differences for 349 SNPs with a p-value of 1% (236 with 10% FDR). Unlike the rest of the genome, these 349 outlier SNPs form two groups associated with each mt-haplotype, with a minority of individuals having mixed ancestry. We use this mixed ancestry in combination with mt-haplotype as a polygenic factor to explain a significant fraction of the individual OxPhos variation. These data suggest that mito-nuclear interactions affect cardiac OxPhos function. The 349 outlier SNPs occur in genes involved in regulating metabolic processes but are not directly associated with the 79 nuclear OxPhos proteins. Therefore, we postulate that the evolution of mito-nuclear interactions affects OxPhos function by acting upstream of OxPhos.

@article{doi101371journalpgen1006517,
    author = "Baris, Tara Z. and Wagner, Dominique N. and Dayan, David I. and Du, Xiao and Blier, Pierre and Pichaud, Nicolas and Oleksiak, Marjorie F. and Crawford, D. L.",
    title = "Evolved genetic and phenotypic differences due to mitochondrial-nuclear interactions",
    year = "2017",
    journal = "PLoS Genetics",
    abstract = "The oxidative phosphorylation (OxPhos) pathway is responsible for most aerobic ATP production and is the only pathway with both nuclear and mitochondrial encoded proteins. The importance of the interactions between these two genomes has recently received more attention because of their potential evolutionary effects and how they may affect human health and disease. In many different organisms, healthy nuclear and mitochondrial genome hybrids between species or among distant populations within a species affect fitness and OxPhos functions. However, what is less understood is whether these interactions impact individuals within a single natural population. The significance of this impact depends on the strength of selection for mito-nuclear interactions. We examined whether mito-nuclear interactions alter allele frequencies for \textasciitilde 11,000 nuclear SNPs within a single, natural Fundulus heteroclitus population containing two divergent mitochondrial haplotypes (mt-haplotypes). Between the two mt-haplotypes, there are significant nuclear allele frequency differences for 349 SNPs with a p-value of 1\% (236 with 10\% FDR). Unlike the rest of the genome, these 349 outlier SNPs form two groups associated with each mt-haplotype, with a minority of individuals having mixed ancestry. We use this mixed ancestry in combination with mt-haplotype as a polygenic factor to explain a significant fraction of the individual OxPhos variation. These data suggest that mito-nuclear interactions affect cardiac OxPhos function. The 349 outlier SNPs occur in genes involved in regulating metabolic processes but are not directly associated with the 79 nuclear OxPhos proteins. Therefore, we postulate that the evolution of mito-nuclear interactions affects OxPhos function by acting upstream of OxPhos.",
    url = "https://doi.org/10.1371/journal.pgen.1006517",
    doi = "10.1371/journal.pgen.1006517",
    openalex = "W2598891531",
    references = "doi101111j1365294x201105290x, doi101111j155856461990tb04277x"
}

Evolutionary genetics has long struggled with understanding how functional genes under selection remain polymorphic in natural populations. Taking as a starting point that natural selection is ultimately a manifestation of ecological processes, we spotlight an underemphasized and potentially ubiquitous ecological effect that may have fundamental effects on the maintenance of genetic variation. Negative frequency dependency is a well-established emergent property of density dependence in ecology, because the relative profitability of different modes of exploiting or utilizing limiting resources tends to be inversely proportional to their frequency in a population. We suggest that this may often generate negative frequency-dependent selection (NFDS) on major effect loci that affect rate-dependent physiological processes, such as metabolic rate, that are phenotypically manifested as polymorphism in pace-of-life syndromes. When such a locus under NFDS shows stable intermediate frequency polymorphism, this should generate epistatic selection potentially involving large numbers of loci with more minor effects on life-history (LH) traits. When alternative alleles at such loci show sign epistasis with a major effect locus, this associative NFDS will promote the maintenance of polygenic variation in LH genes. We provide examples of the kind of major effect loci that could be involved and suggest empirical avenues that may better inform us on the importance and reach of this process.

@article{doi101111mec17062,
    author = "Arnqvist, Göran and Rowe, Locke",
    title = "Ecology, the pace‐of‐life, epistatic selection and the maintenance of genetic variation in life‐history genes",
    year = "2023",
    journal = "Molecular Ecology",
    abstract = "Evolutionary genetics has long struggled with understanding how functional genes under selection remain polymorphic in natural populations. Taking as a starting point that natural selection is ultimately a manifestation of ecological processes, we spotlight an underemphasized and potentially ubiquitous ecological effect that may have fundamental effects on the maintenance of genetic variation. Negative frequency dependency is a well-established emergent property of density dependence in ecology, because the relative profitability of different modes of exploiting or utilizing limiting resources tends to be inversely proportional to their frequency in a population. We suggest that this may often generate negative frequency-dependent selection (NFDS) on major effect loci that affect rate-dependent physiological processes, such as metabolic rate, that are phenotypically manifested as polymorphism in pace-of-life syndromes. When such a locus under NFDS shows stable intermediate frequency polymorphism, this should generate epistatic selection potentially involving large numbers of loci with more minor effects on life-history (LH) traits. When alternative alleles at such loci show sign epistasis with a major effect locus, this associative NFDS will promote the maintenance of polygenic variation in LH genes. We provide examples of the kind of major effect loci that could be involved and suggest empirical avenues that may better inform us on the importance and reach of this process.",
    url = "https://doi.org/10.1111/mec.17062",
    doi = "10.1111/mec.17062",
    openalex = "W4382632412",
    references = "doi101093icbicz124"
}

Signals of natural selection can be quickly eroded in high gene flow systems, curtailing efforts to understand how and when genetic adaptation occurs in the ocean. This long-standing, unresolved topic in ecology and evolution has renewed importance because changing environmental conditions are driving range expansions that may necessitate rapid evolutionary responses. One example occurs in Kellet's whelk (Kelletia kelletii), a common subtidal gastropod with an ~40- to 60-day pelagic larval duration that expanded their biogeographic range northwards in the 1970s by over 300 km. To test for genetic adaptation, we performed a series of experimental crosses with Kellet's whelk adults collected from their historical (HxH) and recently expanded range (ExE), and conducted RNA-Seq on offspring that we reared in a common garden environment. We identified 2770 differentially expressed genes (DEGs) between 54 offspring samples with either only historical range (HxH offspring) or expanded range (ExE offspring) ancestry. Using SNPs called directly from the DEGs, we assigned samples of known origin back to their range of origin with unprecedented accuracy for a marine species (92.6% and 94.5% for HxH and ExE offspring, respectively). The SNP with the highest predictive importance occurred on triosephosphate isomerase (TPI), an essential metabolic enzyme involved in cold stress response. TPI was significantly upregulated and contained a non-synonymous mutation in the expanded range. Our findings pave the way for accurately identifying patterns of dispersal, gene flow and population connectivity in the ocean by demonstrating that experimental transcriptomics can reveal mechanisms for how marine organisms respond to changing environmental conditions.

@article{doi101111mec17511,
    author = "Lee, Andy and Daniels, Benjamin N. and Hemstrom, William and López, Cataixa and Kagaya, Yuki and Kihara, Daisuke and Davidson, Jean M. and Toonen, Robert J. and White, Crow and Christie, Mark R.",
    title = "Genetic adaptation despite high gene flow in a range‐expanding population",
    year = "2024",
    journal = "Molecular Ecology",
    abstract = "Signals of natural selection can be quickly eroded in high gene flow systems, curtailing efforts to understand how and when genetic adaptation occurs in the ocean. This long-standing, unresolved topic in ecology and evolution has renewed importance because changing environmental conditions are driving range expansions that may necessitate rapid evolutionary responses. One example occurs in Kellet's whelk (Kelletia kelletii), a common subtidal gastropod with an \textasciitilde 40- to 60-day pelagic larval duration that expanded their biogeographic range northwards in the 1970s by over 300 km. To test for genetic adaptation, we performed a series of experimental crosses with Kellet's whelk adults collected from their historical (HxH) and recently expanded range (ExE), and conducted RNA-Seq on offspring that we reared in a common garden environment. We identified 2770 differentially expressed genes (DEGs) between 54 offspring samples with either only historical range (HxH offspring) or expanded range (ExE offspring) ancestry. Using SNPs called directly from the DEGs, we assigned samples of known origin back to their range of origin with unprecedented accuracy for a marine species (92.6\% and 94.5\% for HxH and ExE offspring, respectively). The SNP with the highest predictive importance occurred on triosephosphate isomerase (TPI), an essential metabolic enzyme involved in cold stress response. TPI was significantly upregulated and contained a non-synonymous mutation in the expanded range. Our findings pave the way for accurately identifying patterns of dispersal, gene flow and population connectivity in the ocean by demonstrating that experimental transcriptomics can reveal mechanisms for how marine organisms respond to changing environmental conditions.",
    url = "https://doi.org/10.1111/mec.17511",
    doi = "10.1111/mec.17511",
    openalex = "W4402094791",
    references = "doi101002evl3189"
}