@article{doi101038202147a0,
    author = "Doolittle, Russell F. and Blombäck, Birger",
    title = "Amino-Acid Sequence Investigations of Fibrinopeptides from Various Mammals: Evolutionary Implications",
    year = "1964",
    journal = "Nature",
    url = "https://doi.org/10.1038/202147a0",
    doi = "10.1038/202147a0",
    openalex = "W2093311325",
    references = "doi1010160006300252902138, doi1010160006300256903936, doi101016s0021925818501319, doi101021ja01639a073, doi101038189704a0, doi1010381921227a0, doi101038193883a0, doi101073pnas48122087, doi101073pnas484613, doi101126science1403566477"
}

@incollection{doi101016b9781483227344500176,
    author = "Zuckerkandl, Emile and Pauling, Linus",
    title = "Evolutionary Divergence and Convergence in Proteins",
    year = "1965",
    booktitle = "Elsevier eBooks",
    url = "https://doi.org/10.1016/b978-1-4832-2734-4.50017-6",
    doi = "10.1016/b978-1-4832-2734-4.50017-6",
    openalex = "W1534406401",
    references = "doi1043249781315081083"
}

@article{doi101016s0022283666802589,
    author = "Fitch, Walter M.",
    title = "An improved method of testing for evolutionary homology",
    year = "1966",
    journal = "Journal of Molecular Biology",
    url = "https://doi.org/10.1016/s0022-2836(66)80258-9",
    doi = "10.1016/s0022-2836(66)80258-9",
    openalex = "W1967627390"
}

@article{doi101093genetics542577,
    author = "Hubby, J L and Lewontin, Richard C",
    title = "A MOLECULAR APPROACH TO THE STUDY OF GENIC HETEROZYGOSITY IN NATURAL POPULATIONS. I. THE NUMBER OF ALLELES AT DIFFERENT LOCI IN DROSOPHILA PSEUDOOBSCURA",
    year = "1966",
    journal = "Genetics",
    abstract = "cornerstone of the theory of evolution by gradual change is that the rate of A evolution is absolutely limited by the amount of genetic variation in the evolving population. FISHER’S “Fundamental Theorem of Natural Selection” (1930) is a mathematical statement of this generalization, but even without mathematics it is clear that genetic change caused by natural selection presupposes genetic differences already existing, on which natural selection can operate. In a sense, a description of the genetic variation in a population is the fundamental datum of evolutionary studies; and it is necessary to explain the origin and maintenance of this variation and to predict its evolutionary consequences. It is not surprising, then, that a major effort of genetics in the last 50 years has been to characterize the amounts and kinds of genetic variation existing in natural or laboratory populations of various organisms. The results so far have told us a great deal about cytological variation such as polymorphisms for inversions and translocations, about frequencies of rare visible mutations at many loci, and about frequencies of chromosomes that are deleterious when homozygous together with the degree of that deleterious effect. In addition, we know of some striking singlelocus polymorphisms. These results are familiar to all students of population genetics and evolution, and have been well reviewed by DOBZHANSKY (195 1) and more recently by MAYR (1 963). Yet, for all the wealth of observation and experiment, the techniques of population genetics have not allowed us to ask directly the most elementary question about the genetic structure of a population: At w h t proportion of his loci can we expect a diploid individual to be heterozygous? Put in another way, this is the question of how much genetic variation there is in any given population. That this question remains unanswered is best shown by a statement of MAYR (1963) at the end of more than 100 pages of review of our present knowledge.",
    url = "https://doi.org/10.1093/genetics/54.2.577",
    doi = "10.1093/genetics/54.2.577",
    openalex = "W1961168765"
}

@article{doi101073pnas581142,
    author = "Sarich, Vincent M. and Wilson, Allan C.",
    title = "Rates of albumin evolution in primates.",
    year = "1967",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = "Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.",
    url = "https://doi.org/10.1073/pnas.58.1.142",
    doi = "10.1073/pnas.58.1.142",
    openalex = "W2095123791",
    references = "doi101002ajpa1330220242, doi1010160003986154904750, doi1010160019279164900527, doi101111j174966321962tb13656x, doi101126science1473660836, doi101126science15137171530, doi101126science15437561563, doi101210endo773563, openalexw2417198282"
}

@article{doi101038217624a0,
    author = "KIMURA, MOTOO",
    title = "Evolutionary Rate at the Molecular Level",
    year = "1968",
    journal = "Nature",
    url = "https://doi.org/10.1038/217624a0",
    doi = "10.1038/217624a0",
    openalex = "W1993351732",
    references = "doi101001jama196603100230164053, doi101007bf02984069, doi101016b9781483227344500176, doi101093genetics16297, doi101093genetics494725, doi101093genetics542577, doi101093genetics542595, doi101098rspb19660032, doi101126science147365368, openalexw2171582839"
}

@article{doi101111j174966321968tb11901x,
    author = "Margoliash, E. and Fitch, W M",
    title = "EVOLUTIONARY VARIABILITY OF CYTOCHROME C PRIMARY STRUCTURES",
    year = "1968",
    journal = "Annals of the New York Academy of Sciences",
    url = "https://doi.org/10.1111/j.1749-6632.1968.tb11901.x",
    doi = "10.1111/j.1749-6632.1968.tb11901.x",
    openalex = "W2026299436",
    references = "doi101016s0021925818969450, doi101016s002192581897184x, doi101021bi00872a016"
}

@article{doi101038224149a0,
    author = "Laird, Charles D. and McConaughy, Betty L. and McCarthy, Brian J.",
    title = "Rate of Fixation of Nucleotide Substitutions in Evolution",
    year = "1969",
    journal = "Nature",
    url = "https://doi.org/10.1038/224149a0",
    doi = "10.1038/224149a0",
    openalex = "W1968561408",
    references = "doi1010160022283668904142, doi101016b9781483227344500176, doi101016c20130119812, doi101016s0022283661800478, doi101016s0022283666800220, doi101038202147a0, doi101038217624a0, doi101073pnas504672, doi101126science147365368, doi101126science1613841529, doi101126science1643881788"
}

@article{doi101073pnas6341181,
    author = "Kimura, Motoo",
    title = "THE RATE OF MOLECULAR EVOLUTION CONSIDERED FROM THE STANDPOINT OF POPULATION GENETICS",
    year = "1969",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = {The rate of amino acid substitutions in the evolution of homologous proteins is remarkably constant. Furthermore, estimated rates of amino acid substitutions based on comparisons of the alpha hemoglobin chains of various mammals with that of the carp are about the same as those based on comparisons of the carp alpha and mammalian beta or the alpha and beta chains in mammals. These uniformities are regarded as evidence for the hypothesis that a majority of amino acid substitutions that occurred in these proteins are the result of random fixation of selectively neutral or nearly neutral mutations. TWO IMPLICATIONS OF THIS POSSIBILITY ARE DISCUSSED: (a) Random gene frequency drift is playing an important role in determining the genetic structure of biological populations and (b) genes in "living fossils" may be expected to have undergone as many DNA base (and therefore amino acid) substitutions as corresponding genes (proteins) in more rapidly evolving species.},
    url = "https://doi.org/10.1073/pnas.63.4.1181",
    doi = "10.1073/pnas.63.4.1181",
    openalex = "W1972639541",
    references = "doi101017s0016672300011459, doi101038201847a0, doi101038217624a0, doi101073pnas484582, doi101073pnas5851895, doi101093genetics613763, doi101111j160152231968tb02169x, doi101126science1643881788"
}

@article{doi101007bf00486096,
    author = "Fitch, Walter M. and Markowitz, Etan",
    title = "An improved method for determining codon variability in a gene and its application to the rate of fixation of mutations in evolution",
    year = "1970",
    journal = "Biochemical Genetics",
    url = "https://doi.org/10.1007/bf00486096",
    doi = "10.1007/bf00486096",
    openalex = "W2029423438"
}

@article{doi101007bf01659391,
    author = "Ohta, Tomoko and Kimura, Motoo",
    title = "On the constancy of the evolutionary rate of cistrons",
    year = "1971",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf01659391",
    doi = "10.1007/bf01659391",
    openalex = "W2083365573",
    references = "doi101073pnas6341181"
}

@article{doi101007bf01659392,
    author = "Dickerson, Richard E.",
    title = "The structure of cytochromec and the rates of molecular evolution",
    year = "1971",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf01659392",
    doi = "10.1007/bf01659392",
    openalex = "W2008265915",
    references = "doi1010160012825266900407"
}

@article{doi1010160022283672903270,
    author = "Jukes, Thomas H. and Holmquist, Richard",
    title = "Estimation of evolutionary changes in certain homologous polypeptide chains",
    year = "1972",
    journal = "Journal of Molecular Biology",
    url = "https://doi.org/10.1016/0022-2836(72)90327-0",
    doi = "10.1016/0022-2836(72)90327-0",
    openalex = "W2078647676",
    references = "doi101007bf00486096, doi101007bf00487738, doi101007bf01659160, doi101007bf01659396, doi1010160006291x68904919, doi1010160022283672903269, doi101016s0021925819770021, doi101126science1633868633"
}

@article{doi101126science1774048530,
    author = "Jukes, T H and Holmquist, R",
    title = "Evolutionary clock: nonconstancy of rate in different species.",
    year = "1972",
    journal = "Science (New York, N.Y.)",
    abstract = "By using various methods for comparing polypeptide sequences we find that the evolutionary divergence of rattlesnake cytochrome c from cytochromes c of species in other classes has been more rapid than that of cytochrome c of another reptile, the snapping turtle. This suggests that the evolutionary rate of change of cytochromes c is species-dependent as well as time-dependent.",
    url = "https://pubmed.ncbi.nlm.nih.gov/5065730/",
    doi = "10.1126/science.177.4048.530",
    openalex = "W1985751472",
    pmid = "5065730",
    references = "doi101007bf01659159, doi1010160022283672903269, doi1010160022283672903270, doi101016s0021925818969450, doi101016s002192581897184x, doi101021bi00872a016, doi101038202147a0, doi101038233604a0, doi101073pnas6341181, doi101126science1553760279"
}

@article{jukes1972evolutionary,
    author = "Jukes, Thomas H. and Holmquist, Richard",
    title = "Evolutionary Clock: Nonconstancy of Rate in Different Species",
    year = "1972",
    journal = "Science",
    abstract = "By using various methods for comparing polypeptide sequences we find that the evolutionary divergence of rattlesnake cytochrome c from cytochromes c of species in other classes has been more rapid than that of cytochrome c of another reptile, the snapping turtle. This suggests that the evolutionary rate of change of cytochromes c is species-dependent as well as time-dependent.",
    url = "https://doi.org/10.1126/science.177.4048.530",
    doi = "10.1126/science.177.4048.530",
    number = "4048",
    openalex = "W1985751472",
    pages = "530-532",
    volume = "177",
    references = "doi101007bf01659159, doi1010160022283672903269, doi1010160022283672903270, doi101016s0021925818969450, doi101016s002192581897184x, doi101021bi00872a016, doi101038202147a0, doi101038233604a0, doi101073pnas6341181, doi101126science1553760279"
}

@misc{jukes1972evolutionary2,
    author = "Jukes, T. H. and Holmquist, W. R",
    title = "Evolutionary clocks; nonconstancy of rate in different species",
    year = "1972",
    howpublished = "Science, v. 177, p. 530-532",
    note = "talkorigins\_source = {true}; raw\_reference = {Jukes, T. H., and Holmquist, W. R., 1972, Evolutionary clocks; nonconstancy of rate in different species: Science, v. 177, p. 530-532.}"
}

@article{doi101007bf01797451,
    author = "Langley, Charles H. and Fitch, Walter M.",
    title = "An examination of the constancy of the rate of molecular evolution",
    year = "1974",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf01797451",
    doi = "10.1007/bf01797451",
    openalex = "W2052694431",
    references = "doi1010079783642884153, doi101007bf01659159, doi101038217624a0, doi101038231114a0, doi101038233604a0, doi101073pnas6341181, doi101093sysbio204406, doi101111j155856461967tb03411x, doi101126science1643881788, doi1023072412116, doi105281zenodo10757649"
}

@article{penny1974evolutionary,
    author = "Penny, David",
    title = "Evolutionary clock: The rate of evolution of rattlesnake cytochromec",
    year = "1974",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf01797452",
    doi = "10.1007/bf01797452",
    number = "3",
    openalex = "W2035113788",
    pages = "179-188",
    volume = "3",
    references = "doi101007bf01659390, doi101007bf01659391, doi101007bf01659392, doi101007bf01659396, doi101016c2013010058x, doi101093sysbio204406, doi1023071441916, doi1023072412116, doi105962bhltitle6856, openalexw2601913882"
}

@article{doi1010160022283675902259,
    author = "de Haën, Christoph and Neurath, Hans and Teller, David C.",
    title = "The phylogeny of trypsin-related serine proteases and their zymogens. New methods for the investigation of distant evolutionary relationships",
    year = "1975",
    journal = "Journal of Molecular Biology",
    url = "https://doi.org/10.1016/0022-2836(75)90225-9",
    doi = "10.1016/0022-2836(75)90225-9",
    openalex = "W1966470624",
    references = "doi1010160022283672903270"
}

@article{doi101111j143210331975tb04062x,
    author = "de Jong, Wilfried W. and van der Ouderaa, F.J.G. and Versteeg, Marlies and Groenewoud, Gerrit and van Amelsvoort, Johan M and Bloemendal, H.",
    title = "Primary Structures of the alpha-Crystallin A Chains of Seven Mammalian Species",
    year = "1975",
    journal = "European Journal of Biochemistry",
    abstract = "The sequence determination of the αA chains of α-crystallin from pig, horse, dog, cat, rabbit, rat and thesus monkey is described. Most residues were placed by homology with the known bovine sequence, after amino acid analyses of tryptic and thermolytic peptides. Sequences were established, using the dansyl-Edman method, whenever peptides differed in composition from the homologous bovine peptides. The number of observed amino acid replacements among these mammalian αA chains is relatively small, but the rate at which substitutions have occurred varies greatly between the different evolutionary lineages. The amino acid replacements are not randomly distributed along the αA chain, most substitutions occurring in the C-terminal part of the chain. The rabbit, rat and monkey αA chains have four substitutions in common, indicating a phylogenetic relationship between these species.",
    url = "https://doi.org/10.1111/j.1432-1033.1975.tb04062.x",
    doi = "10.1111/j.1432-1033.1975.tb04062.x",
    openalex = "W2043847621",
    references = "penny1974evolutionary"
}

@article{doi101111j155856461975tb00851x,
    author = "Felsenstein, Joseph",
    title = "THE GENETIC BASIS OF EVOLUTIONARY CHANGE",
    year = "1975",
    journal = "Evolution",
    url = "https://doi.org/10.1111/j.1558-5646.1975.tb00851.x",
    doi = "10.1111/j.1558-5646.1975.tb00851.x",
    openalex = "W1547248981"
}

@article{doi101007bf01730998,
    author = "Mazin, A L",
    title = "Evolution of DNA structure: Direction, mechanism, rate",
    year = "1976",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf01730998",
    doi = "10.1007/bf01730998",
    openalex = "W2059549140",
    references = "penny1974evolutionary"
}

@article{doi101007bf01796122,
    author = "Prager, Ellen M. and Wilson, Allan C.",
    title = "Congruency of phylogenies derived from different proteins",
    year = "1976",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf01796122",
    doi = "10.1007/bf01796122",
    openalex = "W2008985528",
    references = "penny1974evolutionary"
}

@article{doi101007bf01751806,
    author = "de Jong, Wilfried W. and Gleaves, J.T. and Boulter, Donald",
    title = "Evolutionary changes ofα-crystallin and the phylogeny of mammalian orders",
    year = "1977",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf01751806",
    doi = "10.1007/bf01751806",
    openalex = "W2077491442",
    references = "penny1974evolutionary"
}

@article{doi101038281605a0,
    author = "Jukes, Thomas H. and King, Jack Lester",
    title = "Evolutionary nucleotide replacements in DNA",
    year = "1979",
    journal = "Nature",
    url = "https://doi.org/10.1038/281605a0",
    doi = "10.1038/281605a0",
    openalex = "W2083747207",
    references = "doi1010160022283672903269"
}

@article{doi101007bf01731581,
    author = "Kimura, Motoo",
    title = "A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences",
    year = "1980",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf01731581",
    doi = "10.1007/bf01731581",
    openalex = "W2065461553",
    references = "doi101007bf01653945, doi101007bf01732067, doi101007bf01732340, doi101016b9781483232119500097, doi101016s0021925817401566, doi101038217624a0, doi101038267275a0, doi101038scientificamerican117998, doi101073pnas7172848, doi101126science1643881788"
}

@article{doi101007bf01734359,
    author = "Felsenstein, Joseph",
    title = "Evolutionary trees from DNA sequences: A maximum likelihood approach",
    year = "1981",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf01734359",
    doi = "10.1007/bf01734359",
    openalex = "W2102424972",
    references = "doi101007bf01659159, doi101007bf01797451, doi101093sysbio223240, doi101093sysbio274401, doi101111j155856461965tb01722x, doi101111j251761611977tb01600x, doi101126science1553760279, doi101159000152448, doi1023072412810, doi1023072412923, openalexw2341059552, openalexw3141390961"
}

@article{doi101146annureves13110182001035,
    author = "Thorpe, J. P.",
    title = "The Molecular Clock Hypothesis: Biochemical Evolution, Genetic Differentiation and Systematics",
    year = "1982",
    journal = "Annual Review of Ecology and Systematics",
    abstract = "should not be any clearcut borderline between them. The major distinction, if any, probably lies in the aims of various workers; the evolutionary geneticist studies organisms with a view to understanding the role and mechanisms of evolution, while the systematist is concerned with the evolution and interrelationships of particular animals or plants insofar as this information will enable him to place populations, species, or other taxa more accurately within an overall taxonomic scheme.",
    url = "https://doi.org/10.1146/annurev.es.13.110182.001035",
    doi = "10.1146/annurev.es.13.110182.001035",
    openalex = "W2160489262",
    references = "doi101007bf00485780, doi101007bf01731581, doi1010160022283672903269, doi1010160022283672903270, doi101016s002192581861823x, doi101038284604a0, doi101073pnas7641967, doi101086282771, doi101093genetics893583, doi101093sysbio242209, doi101111j155856461975tb00851x, doi101126science1613841529, doi101126science1774048530, doi104324978020376680411, jukes1972evolutionary, openalexw1567849582"
}

@article{doi101007bf02100628,
    author = "Li, Wen‐Hsiung and Wu, Chung‐I and Luo, Chi‐Cheng",
    title = "Nonrandomness of point mutation as reflected in nucleotide substitutions in pseudogenes and its evolutionary implications",
    year = "1984",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf02100628",
    doi = "10.1007/bf02100628",
    openalex = "W2028961943",
    references = "doi1010160022283672903269"
}

@article{doi101073pnas8261741,
    author = "Wu, Chung‐I and Li, Wen‐Hsiung",
    title = "Evidence for higher rates of nucleotide substitution in rodents than in man.",
    year = "1985",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = "When the coding regions of 11 genes from rodents (mouse or rat) and man are compared with those from another mammalian species (usually bovine), it is found that rodents evolve significantly faster than man. The ratio of the number of nucleotide substitutions in the rodent lineage to that in the human lineage since their divergence is 2.0 for synonymous substitutions and 1.3 for nonsynonymous substitutions. Rodents also evolve faster in the 5' and 3' untranslated regions of five different mRNAs; the ratios are 2.6 and 3.1, respectively. The numbers of nucleotide substitutions between members of the beta-globin gene family that were duplicated before the man-mouse split are also higher in mouse than in man. The difference is, again, greater for synonymous substitutions than for nonsynonymous substitutions. This tendency is more consistent with the neutralist view of molecular evolution than with the selectionist view. A simple explanation for the higher rates in rodents is that rodents have shorter generation times and, thus, higher mutation rates. The implication of our findings for the study of molecular phylogeny is discussed.",
    url = "https://doi.org/10.1073/pnas.82.6.1741",
    doi = "10.1073/pnas.82.6.1741",
    openalex = "W1997188744",
    references = "doi101038224149a0"
}

@article{doi101111j109583121985tb02048x,
    author = "Wilson, Allan C. and Cann, Rebecca L. and Carr, Steven M. and George, Matthew and GYLLENSTEN, ULF B. and Helm‐Bychowski, Kathleen and Higuchi, Russell and Palumbi, Stephen R. and Prager, Ellen M. and Sage, Richard D. and Stoneking, Mark",
    title = "Mitochondrial DNA and two perspectives on evolutionary genetics",
    year = "1985",
    journal = "Biological Journal of the Linnean Society",
    abstract = "Journal Article Mitochondrial DNA and two perspectives on evolutionary genetics Get access ALLAN C. WILSON, ALLAN C. WILSON 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A Search for other works by this author on: Oxford Academic Google Scholar REBECCA L. CANN, REBECCA L. CANN 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A2Howard Hughes Medical Institute, U426, University of California, San Francisco, California 94143, U.S.A Search for other works by this author on: Oxford Academic Google Scholar STEVEN M. CARR, STEVEN M. CARR 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A3Wildlife Genetics Laboraiory, Department of Wildlge and Fisheries Sciences, Texas A \& M University, College Station, Texas 77843, U.S.A Search for other works by this author on: Oxford Academic Google Scholar MATTHEW GEORGE, MATTHEW GEORGE 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A4Department of Biochemistry, Howard University, Washington, DC 20059, U.S.A Search for other works by this author on: Oxford Academic Google Scholar ULF B. GYLLENSTEN, ULF B. GYLLENSTEN 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A5Department of Clinical Genetics, Karolinska Hospital, Box 60500, S-104 01 Stockholm, Sweden Search for other works by this author on: Oxford Academic Google Scholar KATHLEEN M. HELM-BYCHOWSKI, KATHLEEN M. HELM-BYCHOWSKI 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A Search for other works by this author on: Oxford Academic Google Scholar RUSSELL G. HIGUCHI, RUSSELL G. HIGUCHI 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A Search for other works by this author on: Oxford Academic Google Scholar STEPHEN R. PALUMBI, STEPHEN R. PALUMBI 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A6Department of Zoology, University of Hawaii, Honolulu, Hawaii 96822, U.S.A Search for other works by this author on: Oxford Academic Google Scholar ELLEN M. PRAGER, ELLEN M. PRAGER 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A Search for other works by this author on: Oxford Academic Google Scholar RICHARD D. SAGE, RICHARD D. SAGE 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A7Museum of Vertebrate Zoology, University of California, Berkeley, California 94720, U.S.A Search for other works by this author on: Oxford Academic Google Scholar... Show more MARK STONEKING MARK STONEKING 1Department of Biochemistry, University of California, Berkeley, California 94720, U.S.A Search for other works by this author on: Oxford Academic Google Scholar Biological Journal of the Linnean Society, Volume 26, Issue 4, December 1985, Pages 375–400, https://doi.org/10.1111/j.1095-8312.1985.tb02048.x Published: 28 June 2008 Article history Accepted: 01 July 1985 Published: 28 June 2008",
    url = "https://doi.org/10.1111/j.1095-8312.1985.tb02048.x",
    doi = "10.1111/j.1095-8312.1985.tb02048.x",
    openalex = "W2065697254",
    references = "doi101038202147a0, doi101073pnas504672, doi101073pnas581142, doi101111j155856461983tb05533x, doi101126science15838051200, doi1023071438156, doi1023072407274, doi107312simp93764, openalexw788933220, sarich1967immunological"
}

@misc{gould1985a1,
    author = "Gould, S. J",
    title = "A clock of evolution",
    year = "1985",
    howpublished = "Natural History Magazine, v. 94, no. 4, p. 12-25",
    note = "talkorigins\_source = {true}; raw\_reference = {Gould, S. J., 1985, A clock of evolution: Natural History Magazine, v. 94, no. 4, p. 12-25.}"
}

@article{doi101126science3082006,
    author = "Britten, Roy J.",
    title = "Rates of DNA Sequence Evolution Differ Between Taxonomic Groups",
    year = "1986",
    journal = "Science",
    abstract = "The mutation rates of DNA sequences during evolution can be estimated from interspecies DNA sequence differences by assaying changes that have little or no effect on the phenotype (neutral mutations). Examination of available measurements shows that rates of DNA change of different phylogenetic groups differ by a factor of 5. The slowest rates are observed for higher primates and some bird lineages, while faster rates are seen in rodents, sea urchins, and drosophila. The rate of DNA sequence change has decreased markedly during primate evolution. The contrast in rates of DNA sequence change is probably due to evolutionary variation and selection of biochemical mechanisms such as DNA replication or repair.",
    url = "https://doi.org/10.1126/science.3082006",
    doi = "10.1126/science.3082006",
    openalex = "W2027574957",
    references = "doi101038233604a0"
}

@article{doi101007bf02111279,
    author = "Kimura, Motoo",
    title = "Molecular evolutionary clock and the neutral theory",
    year = "1987",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf02111279",
    doi = "10.1007/bf02111279",
    openalex = "W1985154076",
    references = "doi10100703064746897, doi101007bf01731581, doi101016b9781483227344500176, doi101038217624a0, doi101038scientificamerican117998, doi101093aesa383396, doi101126science1774048530, doi101146annurevbi46070177003041, jukes1972evolutionary, openalexw2062594085, openalexw2601913882"
}

@article{doi101007bf02111284,
    author = "Jukes, Thomas H.",
    title = "Transitions, transversions, and the molecular evolutionary clock",
    year = "1987",
    journal = "Journal of Molecular Evolution",
    url = "https://doi.org/10.1007/bf02111284",
    doi = "10.1007/bf02111284",
    openalex = "W1990171433",
    references = "doi101001jama193802790100062037, doi101007bf01731581, doi101007bf01734101, doi101007bf02099755, doi1010160022283672903269, doi1010160022283672903270, doi1010160022283682901371, doi1010160092867481903007, doi101016b9781483227344500176, doi101016b9781483232119500097, doi101038171964b0, doi101038290457a0, doi101126science1774048530, jukes1972evolutionary"
}

@book{doi107312nei92038,
    author = "Nei, Masatoshi",
    title = "Molecular Evolutionary Genetics",
    year = "1987",
    booktitle = "Columbia University Press eBooks",
    url = "https://doi.org/10.7312/nei-92038",
    doi = "10.7312/nei-92038",
    openalex = "W93588716"
}

@article{doi101093genetics1321269,
    author = "Muse, Spencer V. and Weir, B. S.",
    title = "Testing for equality of evolutionary rates.",
    year = "1992",
    journal = "Genetics",
    abstract = "A likelihood ratio test is presented for comparing rates of evolutionary change in the paths of descent leading to two species. The test is compared to previous relative rate tests based on variances of estimated numbers of base substitutions. The likelihood approach allows for different transversion and transition rates, and when these rates are actually different, the likelihood ratio test can be much more powerful than the variance-based tests. For single-parameter mutation models, however, the two tests have similar power. The tests are applied to a set of chloroplast sequences from several species of grasses, and additional indications of significantly different rates leading to barley were found with the likelihood ratio test.",
    url = "https://doi.org/10.1093/genetics/132.1.269",
    doi = "10.1093/genetics/132.1.269",
    openalex = "W2111694912"
}

@article{doi101093oxfordjournalsmolbeva040735,
    author = "Avise, John C. and Bowen, Brian W. and Lamb, Trip and Meylan, Anne B. and Bermingham, Eldredge",
    title = "Mitochondrial DNA evolution at a turtle's pace: evidence for low genetic variability and reduced microevolutionary rate in the Testudines.",
    year = "1992",
    journal = "Molecular Biology and Evolution",
    abstract = {Evidence is compiled suggesting a slowdown in mean microevolutionary rate for turtle mitochondrial DNA (mtDNA). Within each of six species or species complexes of Testudines, representing six genera and three taxonomic families, sequence divergence estimates derived from restriction assays are consistently lower than expectations based on either (a) the dates of particular geographic barriers with which significant mtDNA genetic clades appear associated or (b) the magnitudes of sequence divergence between mtDNA clades in nonturtle species that otherwise exhibit striking phylogeographic concordance with the genetic partitions in turtles. Magnitudes of the inferred rate slowdowns average eightfold relative to the "conventional" mtDNA clock calibration of 2\%/Myr sequence divergence between higher animal lineages. Reasons for the postulated deceleration remain unknown, but two intriguing correlates are (a) the exceptionally long generation length most turtles and (b) turtles' low metabolic rate. Both factors have been suspected of influencing evolutionary rates in the DNA sequences of some other vertebrate groups. Uncertainities about the dates of cladogenetic events in these Testudines leave room for alternatives to the slowdown interpretation, but consistency in the direction of the inferred pattern, across several turtle species and evolutionary settings, suggests the need for caution in acceptance of a universal mtDNA-clock calibration for higher animals.},
    url = "https://doi.org/10.1093/oxfordjournals.molbev.a040735",
    doi = "10.1093/oxfordjournals.molbev.a040735",
    openalex = "W2146549494",
    references = "doi101038233604a0"
}

@article{doi101093genetics1352599,
    author = "Tajima, Fumio",
    title = "Simple methods for testing the molecular evolutionary clock hypothesis.",
    year = "1993",
    journal = "Genetics",
    abstract = "Simple statistical methods for testing the molecular evolutionary clock hypothesis are developed which can be applied to both nucleotide and amino acid sequences. These methods are based on the chi-square test and are applicable even when the pattern of substitution rates is unknown and/or the substitution rate varies among different sites. Furthermore, some of the methods can be applied even when the outgroup is unknown. Using computer simulations, these methods were compared with the likelihood ratio test and the relative rate test. The results indicate that the powers of the present methods are similar to those of the likelihood ratio test and the relative rate test, in spite of the fact that the latter two tests assume that the pattern of substitution rates follows a certain model and that the substitution rate is the same among different sites, while such assumptions are not necessary to apply the present methods. Therefore, the present methods might be useful.",
    url = "https://doi.org/10.1093/genetics/135.2.599",
    doi = "10.1093/genetics/135.2.599",
    openalex = "W2133104753"
}

@article{doi101006jmbi19960167,
    author = "Lichtarge, Olivier and Bourne, Henry R. and Cohen, Fred E.",
    title = "An Evolutionary Trace Method Defines Binding Surfaces Common to Protein Families",
    year = "1996",
    journal = "Journal of Molecular Biology",
    url = "https://doi.org/10.1006/jmbi.1996.0167",
    doi = "10.1006/jmbi.1996.0167",
    openalex = "W2137991504"
}

@article{doi101093oxfordjournalsmolbeva025558,
    author = "Krajewski, Carey and King, David G.",
    title = "Molecular divergence and phylogeny: rates and patterns of cytochrome b evolution in cranes",
    year = "1996",
    journal = "Molecular Biology and Evolution",
    abstract = "Analyses of complete cytochrome b sequences from all species of cranes (Aves: Gruidae) reveal aspects of sequence evolution in the early stages of divergence. These DNA sequences are > or = 89\% identical, but expected departures from random substitution are evident. Silent, third-position pyrimidine transitions are the dominant substitution type, with transversion comprising only a small fraction of sequence differences. Substitution patterns are not clearly manifested until divergence has reached a moderate level (> 3\%), as expected for a stochastic process. Variation in the frequency of mismatch types among lineages decreases at larger divergences, but the level of bias does not decay. Divergence varies up to fivefold among gene regions but is not correlated with structural domain. All protein structural domains except extramembrane 4 display < 20\% variable residues. Regions corresponding to putative functional domains show the excepted conservation of amino acids, although the C-terminal portion of the Q0 reaction center displays several nonconservative replacements. Phylogenetic analyses incorporating substitution asymmetries produced mixed results. Distances estimated with multiple parameters (transition, codon-position, composition, and pyrimidine-transition biases) yielded identical additive tree topologies with comparable bootstrap values, all consistent with uncontroversial species relationships. Maximum likelihood analysis incorporating these biases, as well as equally weighted parsimony analysis, produced similar results. Static, differential weighting for parsimony did not improve the phylogenetic signal but produced unusual trees with low bootstraps. The overall rate of nucleotide substitution varies slightly but significantly among cranes, and calibration of distances against fossil dates suggests divergence rates of 0.7\%-1.7\% per million years.",
    url = "https://doi.org/10.1093/oxfordjournals.molbev.a025558",
    doi = "10.1093/oxfordjournals.molbev.a025558",
    openalex = "W2123687003",
    references = "doi101007bf02111284"
}

@article{doi101111j155856461996tb02342x,
    author = "Wagner, Andreas",
    title = "DOES EVOLUTIONARY PLASTICITY EVOLVE?",
    year = "1996",
    journal = "Evolution",
    abstract = {During the development of a multicellular organism from a zygote, a large number of epigenetic interactions take place on every level of suborganismal organization. This raises the possibility that the system of epigenetic interactions may compensate or "buffer" some of the changes that occur as mutations on its lowest levels, and thus stabilize the phenotype with respect to mutations. This hypothetical phenomenon will be called "epigenetic stability." Its potential importance stems from the fact that phenotypic variation with a genetic basis is an essential prerequisite for evolution. Thus, variation in epigenetic stability might profoundly affect attainable rates of evolution. While representing a systemic property of a developmental system, epigenetic stability might itself be genetically determined and thus be subject to evolutionary change. Whether or not this is the case should ideally be answered directly, that is, by experimentation. The time scale involved and our insufficient quantitative understanding of developmental pathways will probably preclude such an approach in the foreseeable future. Preliminary answers are sought here by using a biochemically motivated model of a small but central part of a developmental pathway. Modeled are sets of transcriptional regulators that mutually regulate each other's expression and thereby form stable gene expression patterns. Such gene-expression patterns, crucially involved in determining developmental pattern formation events, are most likely subject to strong stabilizing natural selection. After long periods of stabilizing selection, the fraction of mutations causing changes in gene-expression patterns is substantially reduced in the model. Epigenetic stability has increased. This phenomenon is found for widely varying regulatory scenarios among transcription factor genes. It is discussed that only epistatic (nonlinear) gene interactions can cause such change in epigenetic stability. Evidence from paleontology, molecular evolution, development, and genetics, consistent with the existence of variation in epigenetic stability, is discussed. The relation of epigenetic stability to developmental canalization is outlined. Experimental scenarios are suggested that may provide further evidence.},
    url = "https://doi.org/10.1111/j.1558-5646.1996.tb02342.x",
    doi = "10.1111/j.1558-5646.1996.tb02342.x",
    openalex = "W1487920553",
    references = "doi101007bf02111279"
}

@article{doi101126science2715248470,
    author = "Doolittle, Russell F. and Feng, Da-Fei and Tsang, Simon K. and Cho, Glen and Little, Elizabeth",
    title = "Determining Divergence Times of the Major Kingdoms of Living Organisms with a Protein Clock",
    year = "1996",
    journal = "Science",
    abstract = "Amino acid sequence data from 57 different enzymes were used to determine the divergence times of the major biological groupings. Deuterostomes and protostomes split about 670 million years ago and plants, animals, and fungi last shared a common ancestor about a billion years ago. With regard to these protein sequences, plants are slightly more similar to animals than are the fungi. In contrast, phylogenetic analysis of the same sequences indicates that fungi and animals shared a common ancestor more recently than either did with plants, the greater difference resulting from the fungal lineage changing faster than the animal and plant lines over the last 965 million years. The major protist lineages have been changing at a somewhat faster rate than other eukaryotes and split off about 1230 million years ago. If the rate of change has been approximately constant, then prokaryotes and eukaryotes last shared a common ancestor about 2 billion years ago, archaebacterial sequences being measurably more similar to eukaryotic ones than are eubacterial ones.",
    url = "https://doi.org/10.1126/science.271.5248.470",
    doi = "10.1126/science.271.5248.470",
    openalex = "W1970473208",
    references = "doi101007bf02101113, doi101007bf02111276, doi101007bf02603120, doi1010160022283670900574, doi101016b9781483227344500176, doi101016b9781483232119500097, doi101038202147a0, doi101038361219a0, doi101073pnas86239355, doi101126science1604319, doi101126science17940781144, doi101126science2605108640, doi101128mr5749539941993, doi1023072412448, doi107312nei92038"
}

@article{doi101093oxfordjournalsmolbeva025731,
    author = "Sanderson, Michael J.",
    title = "A Nonparametric Approach to Estimating Divergence Times in the Absence of Rate Constancy",
    year = "1997",
    journal = "Molecular Biology and Evolution",
    abstract = "A new method for estimating divergence times when evolutionary rates are variable across lineages is proposed. The method, called nonparametric rate smoothing (NPRS), relies on minimization of ancestor-descendant local rate changes and is motivated by the likelihood that evolutionary rates are autocorrelated in time. Fossil information pertaining to minimum and/or maximum ages of nodes in a phylogeny is incorporated into the algorithms by constrained optimization techniques. The accuracy of NPRS was examined by comparison to a clock-based maximum-likelihood method in computer simulations. NPRS provides more accurate estimates of divergence times when (1) sequence lengths are sufficiently long, (2) rates are truly nonclocklike, and (3) rates are moderately to highly autocorrelated in time. The algorithms were applied to estimate divergence times in seed plants based on data from the chloroplast rbcL gene. Both constrained and unconstrained NPRS methods tended to produce divergence time estimates more consistent with paleobotanical evidence than did clock-based estimates.",
    url = "https://doi.org/10.1093/oxfordjournals.molbev.a025731",
    doi = "10.1093/oxfordjournals.molbev.a025731",
    openalex = "W1964575260",
    references = "doi101007bf01797451, doi101126science2715248470, doi10113000917613198311503tdonag20co2"
}

@article{doi101093oxfordjournalsmolbeva025892,
    author = "Thorne, Jeffrey L. and Kishino, Hirohisa and Painter, Ian",
    title = "Estimating the rate of evolution of the rate of molecular evolution",
    year = "1998",
    journal = "Molecular Biology and Evolution",
    abstract = "A simple model for the evolution of the rate of molecular evolution is presented. With a Bayesian approach, this model can serve as the basis for estimating dates of important evolutionary events even in the absence of the assumption of constant rates among evolutionary lineages. The method can be used in conjunction with any of the widely used models for nucleotide substitution or amino acid replacement. It is illustrated by analyzing a data set of rbcL protein sequences.",
    url = "https://doi.org/10.1093/oxfordjournals.molbev.a025892",
    doi = "10.1093/oxfordjournals.molbev.a025892",
    openalex = "W2051296828",
    references = "doi101007bf01734359, doi101007bf01797451, doi101007bf02111276, doi101007bf02338839, doi101016b9781483227344500176, doi101016b9781483232119500097, doi101038scientificamerican117998, doi101093bioinformatics83275, doi101093biomet57197, doi101198tech2001s608, doi1012019780429258411, doi1023072291187"
}

@article{doi101098rspb19980568,
    author = "Knowlton­, Nancy­ and Weigt, Lee A.",
    title = "New dates and new rates for divergence across the Isthmus of Panama",
    year = "1998",
    journal = "Proceedings of the Royal Society B Biological Sciences",
    abstract = "Sister species separated by the Isthmus of Panama have been widely used to estimate rates of molecular evolution. These estimates are based on the assumption that geographic isolation occurred nearly simulta-neously for most taxa, when connections between the Caribbean and eastern Paci¢c closed approximately three million years ago. Here we show that this assumption is invalid for the only genus for which many taxa and multiple genetic markers have been analysed. Patterns of divergence exhibited by allozymes and the mitochondrial COI gene are highly concordant for 15 pairs of snapping shrimp in the genus Alpheus, indicating that they provide a reasonable basis for estimating time since cessation of gene £ow. The extent of genetic divergence between pairs of sister species varied over fourfold. Sister species from mangrove environments showed the least divergence, as would be expected if these were among the last habitats to be divided. Using this pair yields a rate of sequence divergence of 1.4 \% per one million years, with implied times of separation for the 15 pairs of 3^18 million years ago. Many past studies may have overestimated rates of molecular evolution because they sampled pairs that were sepa-rated well before ¢nal closure of the Isthmus.",
    url = "https://doi.org/10.1098/rspb.1998.0568",
    doi = "10.1098/rspb.1998.0568",
    openalex = "W2053565808",
    references = "doi101007978303487527124, doi101038280599a0, doi101126science25350241099"
}

@article{doi101126science28354061310,
    author = "Foote, Mike and Hunter, John P. and Janis, Christine M. and Sepkoski, J. John",
    title = "Evolutionary and Preservational Constraints on Origins of Biologic Groups: Divergence Times of Eutherian Mammals",
    year = "1999",
    journal = "Science",
    abstract = "Some molecular clock estimates of divergence times of taxonomic groups undergoing evolutionary radiation are much older than the groups' first observed fossil record. Mathematical models of branching evolution are used to estimate the maximal rate of fossil preservation consistent with a postulated missing history, given the sum of species durations implied by early origins under a range of species origination and extinction rates. The plausibility of postulated divergence times depends on origination, extinction, and preservation rates estimated from the fossil record. For eutherian mammals, this approach suggests that it is unlikely that many modern orders arose much earlier than their oldest fossil records.",
    url = "https://doi.org/10.1126/science.283.5406.1310",
    doi = "10.1126/science.283.5406.1310",
    openalex = "W2051714097",
    references = "doi101007bf02111279"
}

@article{doi101016s0169534700018760,
    author = "Crandall, Keith A. and Crandall, Keith A. and Bininda‐Emonds, Olaf R. P. and Bininda‐Emonds, Olaf R. P. and Mace, Georgina M. and Mace, Georgina M. and Wayne, Robert K. and Wayne, Robert K.",
    title = "Considering evolutionary processes in conservation biology",
    year = "2000",
    journal = "Trends in Ecology \& Evolution",
    url = "https://doi.org/10.1016/s0169-5347(00)01876-0",
    doi = "10.1016/s0169-5347(00)01876-0",
    openalex = "W2125936169",
    references = "doi1010079781461523819, doi101146annureves16110185002141, doi1023072409350, doi1023072409372"
}

@article{doi101093bioinformatics17121244,
    author = "Kumar, Sudhir and Tamura, Koichiro and Jakobsen, Ingrid B. and Nei, Masatoshi",
    title = "MEGA2: molecular evolutionary genetics analysis software",
    year = "2001",
    journal = "Bioinformatics",
    abstract = "s.kumar@asu.edu",
    url = "https://doi.org/10.1093/bioinformatics/17.12.1244",
    doi = "10.1093/bioinformatics/17.12.1244",
    openalex = "W2156434383",
    references = "doi101007bf00173196, doi101093bioinformatics102189, doi101093oso97801951358480010001, doi101093oxfordjournalsmolbeva040259, doi102307jctvcm4gbm10, openalexw2002446259"
}

@article{doi101093oxfordjournalsmolbeva003974,
    author = "Sanderson, Michael J.",
    title = "Estimating Absolute Rates of Molecular Evolution and Divergence Times: A Penalized Likelihood Approach",
    year = "2002",
    journal = "Molecular Biology and Evolution",
    abstract = "Rates of molecular evolution vary widely between lineages, but quantification of how rates change has proven difficult. Recently proposed estimation procedures have mainly adopted highly parametric approaches that model rate evolution explicitly. In this study, a semiparametric smoothing method is developed using penalized likelihood. A saturated model in which every lineage has a separate rate is combined with a roughness penalty that discourages rates from varying too much across a phylogeny. A data-driven cross-validation criterion is then used to determine an optimal level of smoothing. This criterion is based on an estimate of the average prediction error associated with pruning lineages from the tree. The methods are applied to three data sets of six genes across a sample of land plants. Optimally smoothed estimates of absolute rates entailed 2- to 10-fold variation across lineages.",
    url = "https://doi.org/10.1093/oxfordjournals.molbev.a003974",
    doi = "10.1093/oxfordjournals.molbev.a003974",
    openalex = "W1982848324",
    references = "doi1010079781475729177, doi1010079781489944733, doi101007bf01797451, doi1010160169534796100410, doi101016s0022519305801043, doi10103831927, doi10106313047872, doi101073pnas9094087, doi101093oxfordjournalsmolbeva025892, doi101093oxfordjournalsmolbeva040259, doi101111j146364091997tb00423x, doi1023071271147, doi105860choice302064, rambaut1998estimating"
}

@article{doi101093oxfordjournalsmolbeva004024,
    author = "Marko, Peter B.",
    title = "Fossil Calibration of Molecular Clocks and the Divergence Times of Geminate Species Pairs Separated by the Isthmus of Panama",
    year = "2002",
    journal = "Molecular Biology and Evolution",
    abstract = {Calibration of nucleotide sequence divergence rates provides an important method by which to test many hypotheses of evolution. In the absence of an adequate fossil record, geological events, rather than the first appearances of sister taxa in the geological record, are often used to calibrate molecular clocks. The formation of the Isthmus of Panama, which isolated the tropical western Atlantic and eastern Pacific oceans, is one such event that is frequently used to infer rates of nucleotide sequence divergence. Isthmian calibrations assume that morphologically similar "geminate" species living now on either side of the isthmus were isolated geographically by the latest stages of seaway closure 3.1-3.5 MYA. Here, I have applied calibration dates from the fossil record to cytochrome c oxidase-1 (CO1) and nuclear histone-3 (H3) divergences among six pairs of geminates in the Arcidae to test this hypothesis. Analysis of CO1 first and third positions yield geminate divergences that predate final seaway closure, and on the basis of CO1 first positions, times for all six geminates are significantly greater than 3.5 Myr. H3 sequences produce much more recent geminate divergences, some that are younger than 3.1 Myr. But H3-derived estimates for all arcid geminates are not significantly different from both 0 and 15 Myr. According to CO1, one of the two most divergent pairs, Arca mutabilis and A. imbricata, split more than 30 MYA. This date is compatible with the fossil record, which indicates that these species were morphologically distinct at least 16-21 MYA. Across all CO1 nucleotide sites, divergence rates for arcids are slower than the rates reported for other taxa on the basis of isthmian calibrations, with the exception of rates determined from the least divergent species pair in larger surveys of multiple transisthmian pairs. Rate differences between arcids and some taxa may be real, but these data suggest that divergence rates can be greatly overestimated when dates corresponding to final closure of the Central American Seaway are used to calibrate the molecular clocks of marine organisms.},
    url = "https://doi.org/10.1093/oxfordjournals.molbev.a004024",
    doi = "10.1093/oxfordjournals.molbev.a004024",
    openalex = "W2125071340",
    references = "doi101007978303487527124, doi101038280599a0"
}

@article{doi101093bioinformatics192301,
    author = "Sanderson, Michael J.",
    title = "r8s: inferring absolute rates of molecular evolution and divergence times in the absence of a molecular clock",
    year = "2003",
    journal = "Bioinformatics",
    abstract = "The linux executable, C source code, sample data sets and user manual are available free at http://ginger.ucdavis.edu/r8s.",
    url = "https://doi.org/10.1093/bioinformatics/19.2.301",
    doi = "10.1093/bioinformatics/19.2.301",
    openalex = "W2159368494",
    references = "doi10103844766, doi101093oxfordjournalsmolbeva003974, doi101093oxfordjournalsmolbeva025892, doi101093oxfordjournalsmolbeva040259, rambaut1998estimating"
}

@article{doi101146annurevecolsys34011802132421,
    author = "Funk, Daniel J. and Omland, Kevin E.",
    title = "Species-Level Paraphyly and Polyphyly: Frequency, Causes, and Consequences, with Insights from Animal Mitochondrial DNA",
    year = "2003",
    journal = "Annual Review of Ecology Evolution and Systematics",
    abstract = "▪ Abstract Many uses of gene trees implicitly assume that nominal species are monophyletic in their alleles at the study locus. However, in well-sampled gene trees, certain alleles in one species may appear more closely related to alleles from different species than to other conspecific alleles. Such deviations from species-level monophyly have a variety of causes and may lead to erroneous evolutionary interpretations if undetected. The present paper describes the causes and consequences of these paraphyletic and polyphyletic patterns. It also provides a detailed literature survey of mitochondrial DNA studies on low-level animal phylogeny and phylogeography, results from which reveal the frequency of nonmonophyly and patterns of interpretation and sampling. This survey detected species-level paraphyly or polyphyly in 23\% of 2319 assayed species, demonstrating this phenomenon to be statistically supported, taxonomically widespread, and far more common than generally recognized. Our findings call for increased attention to sampling and the interpretation of paraphyletic and polyphyletic gene trees in studies of closely related taxa by systematists and population geneticists alike and thus for a new tradition of “congeneric phylogeography.”",
    url = "https://doi.org/10.1146/annurev.ecolsys.34.011802.132421",
    doi = "10.1146/annurev.ecolsys.34.011802.132421",
    openalex = "W2112061642",
    references = "doi1010079781461523819, doi101016s0169534701021619, doi101080106351502753475880, doi101093sysbio463523, doi101098rspb19990641, doi101111j155856461988tb02497x, doi1023072408870, doi1023072419070, doi102307jctv1nzfgj7"
}

@article{doi101073pnas0407735101,
    author = "Gillooly, James F. and Allen, Andrew P. and West, Geoffrey B. and Brown, James H.",
    title = "The rate of DNA evolution: Effects of body size and temperature on the molecular clock",
    year = "2004",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = {Observations that rates of molecular evolution vary widely within and among lineages have cast doubts on the existence of a single "molecular clock." Differences in the timing of evolutionary events estimated from genetic and fossil evidence have raised further questions about the accuracy of molecular clocks. Here, we present a model of nucleotide substitution that combines theory on metabolic rate with the now-classic neutral theory of molecular evolution. The model quantitatively predicts rate heterogeneity and may reconcile differences in molecular- and fossil-estimated dates of evolutionary events. Model predictions are supported by extensive data from mitochondrial and nuclear genomes. By accounting for the effects of body size and temperature on metabolic rate, this model explains heterogeneity in rates of nucleotide substitution in different genes, taxa, and thermal environments. This model also suggests that there is indeed a single molecular clock, as originally proposed by Zuckerkandl and Pauling [Zuckerkandl, E. \& Pauling, L. (1965) in Evolving Genes and Proteins, eds. Bryson, V. \& Vogel, H. J. (Academic, New York), pp. 97-166], but that it "ticks" at a constant substitution rate per unit of mass-specific metabolic energy rather than per unit of time. This model therefore links energy flux and genetic change. More generally, the model suggests that body size and temperature combine to control the overall rate of evolution through their effects on metabolism.},
    url = "https://doi.org/10.1073/pnas.0407735101",
    doi = "10.1073/pnas.0407735101",
    openalex = "W2152092111",
    references = "doi101038224149a0, doi101038nrg1020, doi101086285558"
}

@article{doi101093bib52150,
    author = "Kumar, Sudhir",
    title = "MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment",
    year = "2004",
    journal = "Briefings in Bioinformatics",
    abstract = "With its theoretical basis firmly established in molecular evolutionary and population genetics, the comparative DNA and protein sequence analysis plays a central role in reconstructing the evolutionary histories of species and multigene families, estimating rates of molecular evolution, and inferring the nature and extent of selective forces shaping the evolution of genes and genomes. The scope of these investigations has now expanded greatly owing to the development of high-throughput sequencing techniques and novel statistical and computational methods. These methods require easy-to-use computer programs. One such effort has been to produce Molecular Evolutionary Genetics Analysis (MEGA) software, with its focus on facilitating the exploration and analysis of the DNA and protein sequence variation from an evolutionary perspective. Currently in its third major release, MEGA3 contains facilities for automatic and manual sequence alignment, web-based mining of databases, inference of the phylogenetic trees, estimation of evolutionary distances and testing evolutionary hypotheses. This paper provides an overview of the statistical methods, computational tools, and visual exploration modules for data input and the results obtainable in MEGA.",
    url = "https://doi.org/10.1093/bib/5.2.150",
    doi = "10.1093/bib/5.2.150",
    openalex = "W2146396346",
    references = "doi101007bf01731581, doi101007bf02407308, doi101016b9781483232119500097, doi101093bioinformatics17121244, doi101093genetics1233585, doi101093nar22224673, doi101093nar25173389, doi101093oso97801951358480010001, doi101093oxfordjournalsmolbeva040023, doi101093oxfordjournalsmolbeva040259, doi101093oxfordjournalsmolbeva040343, doi101093oxfordjournalsmolbeva040410, doi101093oxfordjournalsmolbeva040454, doi101093oxfordjournalsmolbeva040771, doi101111j155856461985tb00420x, doi1023072408678, doi1023072412074, doi105860choice392183, openalexw2032279931, openalexw3217097258"
}

@misc{kumar2004molecular,
    author = "Kumar, Sudhir and Filipski, Alan",
    title = "Molecular Clock (Evolutionary Clock, Rate of Evolution)",
    year = "2004",
    booktitle = "Dictionary of Bioinformatics and Computational Biology",
    url = "https://doi.org/10.1002/9780471650126.dob0452.pub2",
    doi = "10.1002/9780471650126.dob0452.pub2"
}

@article{doi101007bf01659390,
    author = "Kimura, M. and Ohta, T.",
    title = "On the rate of molecular evolution",
    year = "2005",
    journal = "Journal of Molecular Evolution",
    url = "https://www.semanticscholar.org/paper/3afccf44513c0dc8ea68c2743b1784d035abcb1c",
    doi = "10.1007/BF01659390",
    is_oa = "true",
    number = "1",
    pages = "1-17",
    semanticscholar_citation_count = "129",
    semanticscholar_id = "3afccf44513c0dc8ea68c2743b1784d035abcb1c",
    volume = "1"
}

@article{doi101038nrg1659,
    author = "Kumar, Sudhir",
    title = "Molecular clocks: four decades of evolution",
    year = "2005",
    journal = "Nature Reviews Genetics",
    url = "https://doi.org/10.1038/nrg1659",
    doi = "10.1038/nrg1659",
    openalex = "W2040940215",
    references = "doi10103818872, doi101038nature03150, doi101073pnas504672, doi101073pnas581142, doi101126science28554362031a, doi105860choice343307"
}

@article{doi101093bibbbn017,
    author = "Kumar, Sudhir and Nei, M and Dudley, Joel T. and Tamura, Koichiro",
    title = "MEGA: A biologist-centric software for evolutionary analysis of DNA and protein sequences",
    year = "2008",
    journal = "Briefings in Bioinformatics",
    abstract = "The Molecular Evolutionary Genetics Analysis (MEGA) software is a desktop application designed for comparative analysis of homologous gene sequences either from multigene families or from different species with a special emphasis on inferring evolutionary relationships and patterns of DNA and protein evolution. In addition to the tools for statistical analysis of data, MEGA provides many convenient facilities for the assembly of sequence data sets from files or web-based repositories, and it includes tools for visual presentation of the results obtained in the form of interactive phylogenetic trees and evolutionary distance matrices. Here we discuss the motivation, design principles and priorities that have shaped the development of MEGA. We also discuss how MEGA might evolve in the future to assist researchers in their growing need to analyze large data set using new computational methods.",
    url = "https://doi.org/10.1093/bib/bbn017",
    doi = "10.1093/bib/bbn017",
    openalex = "W2110899053",
    references = "doi101086383584, doi101093acprofoso97801985670280010001, doi101093bib52150, doi101093bioinformatics17121244, doi101093molbevmsm092, doi101093oso97801951358480010001, doi101093oxfordjournalsmolbeva040259, doi107312nei92038"
}

@article{doi101093molbevmsn148,
    author = "Burgess, Ralph and Yang, Ziheng",
    title = "Estimation of Hominoid Ancestral Population Sizes under Bayesian Coalescent Models Incorporating Mutation Rate Variation and Sequencing Errors",
    year = "2008",
    journal = "Molecular Biology and Evolution",
    abstract = "Estimation of population parameters for the common ancestors of humans and the great apes is important in understanding our evolutionary history. In particular, inference of population size for the human-chimpanzee common ancestor may shed light on the process by which the 2 species separated and on whether the human population experienced a severe size reduction in its early evolutionary history. In this study, the Bayesian method of ancestral inference of Rannala and Yang (2003. Bayes estimation of species divergence times and ancestral population sizes using DNA sequences from multiple loci. Genetics. 164:1645-1656) was extended to accommodate variable mutation rates among loci and random species-specific sequencing errors. The model was applied to analyze a genome-wide data set of approximately 15,000 neutral loci (7.4 Mb) aligned for human, chimpanzee, gorilla, orangutan, and macaque. We obtained robust and precise estimates for effective population sizes along the hominoid lineage extending back approximately 30 Myr to the cercopithecoid divergence. The results showed that ancestral populations were 5-10 times larger than modern humans along the entire hominoid lineage. The estimates were robust to the priors used and to model assumptions about recombination. The unusually low X chromosome divergence between human and chimpanzee could not be explained by variation in the male mutation bias or by current models of hybridization and introgression. Instead, our parameter estimates were consistent with a simple instantaneous process for human-chimpanzee speciation but showed a major reduction in X chromosome effective population size peculiar to the human-chimpanzee common ancestor, possibly due to selective sweeps on the X prior to separation of the 2 species.",
    url = "https://doi.org/10.1093/molbev/msn148",
    doi = "10.1093/molbev/msn148",
    openalex = "W2100244203",
    references = "doi101007bf02111284"
}

@article{doi101111j1365294x200803742x,
    author = "Weir, Jason T. and Schluter, Dolph",
    title = "Calibrating the avian molecular clock",
    year = "2008",
    journal = "Molecular Ecology",
    abstract = "Molecular clocks are widely used to date phylogenetic events, yet evidence supporting the rate constancy of molecular clocks through time and across taxonomic lineages is weak. Here, we present 90 candidate avian clock calibrations obtained from fossils and biogeographical events. Cross-validation techniques were used to identify and discard 16 inconsistent calibration points. Molecular evolution occurred in an approximately clock-like manner through time for the remaining 74 calibrations of the mitochondrial gene, cytochrome b. A molecular rate of approximately 2.1\% (+/- 0.1\%, 95\% confidence interval) was maintained over a 12-million-year interval and across most of 12 taxonomic orders. Minor but significant variance in rates occurred across lineages but was not explained by differences in generation time, body size or latitudinal distribution as previously suggested.",
    url = "https://doi.org/10.1111/j.1365-294x.2008.03742.x",
    doi = "10.1111/j.1365-294x.2008.03742.x",
    openalex = "W1908311700",
    references = "doi101038224149a0, doi10103823231, doi101046j1365294x200001020x, doi101073pnas0401892101"
}

@article{doi104172jcsb1000009,
    author = "Huang, Shi",
    title = "The Genetic Equidistance Result of Molecular Evolution is Independent of Mutation Rates",
    year = "2008",
    journal = "Journal of Computer Science \& Systems Biology",
    abstract = "The well-established genetic equidistance result shows that sister species are approximately equidistant to a simpler outgroup as measured by DNA or protein dissimilarity. The equidistance result is the most direct evidence, and remains the only evidence, for the constant mutation rate interpretation of this result, known as the molecular clock. However, data independent of the equidistance result have steadily accumulated in recent years that often violate a constant mutation rate. Many have automatically inferred non-equidistance whenever a non-constant mutation rate was observed, based on the unproven assumption that the equidistance result is an outcome of constant mutation rate. Here it is shown that the equidistance result remains valid even when different species can be independently shown to have different mutation rates. A random sampling of 50 proteins shows that nearly all proteins display the equidistance result despite the fact that many proteins have non-constant mutation rates. Therefore, the genetic equidistance result does not necessarily mean a constant mutation rate. Observations of different mutation rates do not invalidate the genetic equidistance result. New ideas are needed to explain the genetic equidistance result that must grant different mutation rates to different species and must be independently testable.",
    url = "https://doi.org/10.4172/jcsb.1000009",
    doi = "10.4172/jcsb.1000009",
    openalex = "W2140859826",
    references = "doi1010079781461523819, doi101016jcell200806021, doi101038217624a0, doi1010382191335a0, doi10103831927, doi101038nature05846, doi101093oso97801951358480010001, doi101126science1553760279, doi101126science1643881788, doi101126science1774048530, doi1023071446738, jukes1972evolutionary"
}

@article{doi101016jcell200907038,
    author = "Halabi, Najeeb and Rivoire, Olivier and Leibler, Stanislas and Ranganathan, Rama",
    title = "Protein Sectors: Evolutionary Units of Three-Dimensional Structure",
    year = "2009",
    journal = "Cell",
    url = "https://doi.org/10.1016/j.cell.2009.07.038",
    doi = "10.1016/j.cell.2009.07.038",
    openalex = "W2151457629",
    references = "doi101006jmbi19960167, doi1010160016003259903680, doi101021cr000033x, doi101093nar25173389, doi101093nar25244876, doi101126science1085515, doi101126science2735275595, doi101126science2865438295, doi101126science7529940, doi101214aoms1177692379"
}

@article{doi101093molbevmsr121,
    author = "Tamura, Koichiro and Peterson, Daniel G. and Peterson, Nora and Stecher, Glen and Nei, M and Kumar, Sudhir",
    title = "MEGA5: Molecular Evolutionary Genetics Analysis Using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods",
    year = "2011",
    journal = "Molecular Biology and Evolution",
    abstract = "Comparative analysis of molecular sequence data is essential for reconstructing the evolutionary histories of species and inferring the nature and extent of selective forces shaping the evolution of genes and species. Here, we announce the release of Molecular Evolutionary Genetics Analysis version 5 (MEGA5), which is a user-friendly software for mining online databases, building sequence alignments and phylogenetic trees, and using methods of evolutionary bioinformatics in basic biology, biomedicine, and evolution. The newest addition in MEGA5 is a collection of maximum likelihood (ML) analyses for inferring evolutionary trees, selecting best-fit substitution models (nucleotide or amino acid), inferring ancestral states and sequences (along with probabilities), and estimating evolutionary rates site-by-site. In computer simulation analyses, ML tree inference algorithms in MEGA5 compared favorably with other software packages in terms of computational efficiency and the accuracy of the estimates of phylogenetic trees, substitution parameters, and rate variation among sites. The MEGA user interface has now been enhanced to be activity driven to make it easier for the use of both beginners and experienced scientists. This version of MEGA is intended for the Windows platform, and it has been configured for effective use on Mac OS X and Linux desktops. It is available free of charge from http://www.megasoftware.net.",
    url = "https://doi.org/10.1093/molbev/msr121",
    doi = "10.1093/molbev/msr121",
    openalex = "W2132632499",
    references = "doi101007bf01734359, doi101007bf02101694, doi10108010635150390235520, doi10108010635150490522304, doi101093bioinformatics149817, doi101093bioinformaticsbtl446, doi101093biomet762297, doi101093oso97801951358480010001, doi101093oxfordjournalsmolbeva040023, doi101093oxfordjournalsmolbeva040454, doi101093sysbiosyq010, doi101111j155856461985tb00420x, doi101186147121055113, openalexw3217097258"
}

@article{doi101111j15585646201101542x,
    author = "Hey, Jody and Pinho, Catarina",
    title = "POPULATION GENETICS AND OBJECTIVITY IN SPECIES DIAGNOSIS",
    year = "2011",
    journal = "Evolution",
    abstract = "Species as evolutionary lineages are expected to show greater evolutionary independence from one another than are populations within species. Two measures of evolutionary independence that stem from the study of isolation-with-migration models, one reflecting the amount of gene exchange and one reflecting the time of separation, were drawn from the literature for a large number of pairs of closely related species and pairs of populations within species. Both measures, for gene flow and time, showed broadly overlapping distributions for pairs of species and for pairs of populations within species. Species on average show more time and less gene flow than populations, but the similarity of the distributions argues against there being a qualitative difference associated with species status, as compared to populations. The two measures of evolutionary independence were similarly correlated with F(ST) estimates, which in turn also showed similar distributions for species comparisons relative to population comparisons. The measures of gene flow and separation time were examined for the capacity to discriminate intraspecific differences from interspecific differences. If used together, the two measures could be used to develop an objective (in the sense of being repeatable) measure for species diagnosis.",
    url = "https://doi.org/10.1111/j.1558-5646.2011.01542.x",
    doi = "10.1111/j.1558-5646.2011.01542.x",
    openalex = "W2103256381",
    references = "doi101111j1474919x201001051x, doi101146annureves13110182001035"
}

@article{doi101371journalpone0028766,
    author = "Marks, Debora S. and Colwell, Lucy J. and Sheridan, Robert P. and Hopf, Thomas A. and Pagnani, Andrea and Zecchina, Riccardo and Sander, Chris",
    title = "Protein 3D Structure Computed from Evolutionary Sequence Variation",
    year = "2011",
    journal = "PLoS ONE",
    abstract = "The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing.In this paper we ask whether we can infer evolutionary constraints from a set of sequence homologs of a protein. The challenge is to distinguish true co-evolution couplings from the noisy set of observed correlations. We address this challenge using a maximum entropy model of the protein sequence, constrained by the statistics of the multiple sequence alignment, to infer residue pair couplings. Surprisingly, we find that the strength of these inferred couplings is an excellent predictor of residue-residue proximity in folded structures. Indeed, the top-scoring residue couplings are sufficiently accurate and well-distributed to define the 3D protein fold with remarkable accuracy.We quantify this observation by computing, from sequence alone, all-atom 3D structures of fifteen test proteins from different fold classes, ranging in size from 50 to 260 residues, including a G-protein coupled receptor. These blinded inferences are de novo, i.e., they do not use homology modeling or sequence-similar fragments from known structures. The co-evolution signals provide sufficient information to determine accurate 3D protein structure to 2.7-4.8 Å C(α)-RMSD error relative to the observed structure, over at least two-thirds of the protein (method called EVfold, details at http://EVfold.org). This discovery provides insight into essential interactions constraining protein evolution and will facilitate a comprehensive survey of the universe of protein structures, new strategies in protein and drug design, and the identification of functional genetic variants in normal and disease genomes.",
    url = "https://doi.org/10.1371/journal.pone.0028766",
    doi = "10.1371/journal.pone.0028766",
    openalex = "W2061042699",
    references = "doi101016jcell200907038"
}

@article{doi101073pnas1210309109,
    author = "Lee, Heewook and Popodi, Ellen and Tang, Haixu and Foster, Patricia L.",
    title = "Rate and molecular spectrum of spontaneous mutations in the bacterium Escherichia coli as determined by whole-genome sequencing",
    year = "2012",
    journal = "Proceedings of the National Academy of Sciences",
    abstract = "Knowledge of the rate and nature of spontaneous mutation is fundamental to understanding evolutionary and molecular processes. In this report, we analyze spontaneous mutations accumulated over thousands of generations by wild-type Escherichia coli and a derivative defective in mismatch repair (MMR), the primary pathway for correcting replication errors. The major conclusions are (i) the mutation rate of a wild-type E. coli strain is \textasciitilde 1 × 10(-3) per genome per generation; (ii) mutations in the wild-type strain have the expected mutational bias for G:C > A:T mutations, but the bias changes to A:T > G:C mutations in the absence of MMR; (iii) during replication, A:T > G:C transitions preferentially occur with A templating the lagging strand and T templating the leading strand, whereas G:C > A:T transitions preferentially occur with C templating the lagging strand and G templating the leading strand; (iv) there is a strong bias for transition mutations to occur at 5'ApC3'/3'TpG5' sites (where bases 5'A and 3'T are mutated) and, to a lesser extent, at 5'GpC3'/3'CpG5' sites (where bases 5'G and 3'C are mutated); (v) although the rate of small (≤4 nt) insertions and deletions is high at repeat sequences, these events occur at only 1/10th the genomic rate of base-pair substitutions. MMR activity is genetically regulated, and bacteria isolated from nature often lack MMR capacity, suggesting that modulation of MMR can be adaptive. Thus, comparing results from the wild-type and MMR-defective strains may lead to a deeper understanding of factors that determine mutation rates and spectra, how these factors may differ among organisms, and how they may be shaped by environmental conditions.",
    url = "https://doi.org/10.1073/pnas.1210309109",
    doi = "10.1073/pnas.1210309109",
    openalex = "W2019385975",
    references = "doi101016jtig201005003"
}

@article{doi101007s114270134452x,
    author = "Hu, Taobo and Long, Mengping and Yuan, Dejian and Zhu, Zhubing and Huang, Yimin and Huang, Shi",
    title = "The genetic equidistance result: misreading by the molecular clock and neutral theory and reinterpretation nearly half of a century later",
    year = "2013",
    journal = "Science China Life Sciences",
    abstract = "In 1963, Margoliash discovered the unexpected genetic equidistance result after comparing cytochrome c sequences from different species. This finding, together with the hemoglobin analyses of Zuckerkandl and Pauling in 1962, directly inspired the ad hoc molecular clock hypothesis. Unfortunately, however, many biologists have since mistakenly viewed the molecular clock as a genuine reality, which in turn inspired Kimura, King, and Jukes to propose the neutral theory of molecular evolution. Many years of studies have found numerous contradictions to the theory, and few today believe in a universal constant clock. What is being neglected, however, is that the failure of the molecular clock hypothesis has left the original equidistance result an unsolved mystery. In recent years, we fortuitously rediscovered the equidistance result, which remains unknown to nearly all researchers. Incorporating the proven virtues of existing evolutionary theories and introducing the novel concept of maximum genetic diversity, we proposed a more complete hypothesis of evolutionary genetics and reinterpreted the equidistance result and other major evolutionary phenomena. The hypothesis may rewrite molecular phylogeny and population genetics and solve major biomedical problems that challenge the existing framework of evolutionary biology.",
    url = "https://doi.org/10.1007/s11427-013-4452-x",
    doi = "10.1007/s11427-013-4452-x",
    openalex = "W2071409429",
    references = "doi1010079781461523819, doi101007bf01797451, doi101016jcell200907038, doi101038217624a0, doi101038224149a0, doi101038nature11247, doi101073pnas504672, doi101093oso97801951358480010001, doi101126science1108190, doi101126science1643881788, doi101126science1774048530, doi104172jcsb1000009, jukes1972evolutionary"
}

@article{doi101093molbevmst197,
    author = "Tamura, Koichiro and Stecher, Glen and Peterson, Daniel S. and Filipski, Alan and Kumar, Sudhir",
    title = "MEGA6: Molecular Evolutionary Genetics Analysis Version 6.0",
    year = "2013",
    journal = "Molecular Biology and Evolution",
    abstract = "The Molecular Evolutionary Genetics Analysis (MEGA) software has matured to contain a large collection of methods and tools of computational molecular evolution. Here, we describe new additions that make MEGA a more comprehensive tool for building timetrees of species, pathogens, and gene families using rapid relaxed-clock methods. Methods for estimating divergence times and confidence intervals are implemented to use probability densities for calibration constraints for node-dating and sequence sampling dates for tip-dating analyses. They are supported by new options for tagging sequences with spatiotemporal sampling information, an expanded interactive Node Calibrations Editor, and an extended Tree Explorer to display timetrees. Also added is a Bayesian method for estimating neutral evolutionary probabilities of alleles in a species using multispecies sequence alignments and a machine learning method to test for the autocorrelation of evolutionary rates in phylogenies. The computer memory requirements for the maximum likelihood analysis are reduced significantly through reprogramming, and the graphical user interface has been made more responsive and interactive for very big data sets. These enhancements will improve the user experience, quality of results, and the pace of biological discovery. Natively compiled graphical user interface and command-line versions of MEGA11 are available for Microsoft Windows, Linux, and macOS from www.megasoftware.net.",
    url = "https://doi.org/10.1093/molbev/mst197",
    doi = "10.1093/molbev/mst197",
    openalex = "W2152207030",
    references = "doi101038scientificamerican117998, doi101073pnas1213199109, doi101093bib52150, doi101093bioinformatics102189, doi101093bioinformatics17121244, doi101093bioinformaticsbts507, doi101093molbevmsr121, doi101093oso97801951358480010001, doi101126science1211028, openalexw3217097258"
}

@article{doi101111mec12953,
    author = "Ho, Simon Y. W. and Duchêne, Sebastián",
    title = "Molecular‐clock methods for estimating evolutionary rates and timescales",
    year = "2014",
    journal = "Molecular Ecology",
    abstract = "The molecular clock presents a means of estimating evolutionary rates and timescales using genetic data. These estimates can lead to important insights into evolutionary processes and mechanisms, as well as providing a framework for further biological analyses. To deal with rate variation among genes and among lineages, a diverse range of molecular-clock methods have been developed. These methods have been implemented in various software packages and differ in their statistical properties, ability to handle different models of rate variation, capacity to incorporate various forms of calibrating information and tractability for analysing large data sets. Choosing a suitable molecular-clock model can be a challenging exercise, but a number of model-selection techniques are available. In this review, we describe the different forms of evolutionary rate heterogeneity and explain how they can be accommodated in molecular-clock analyses. We provide an outline of the various clock methods and models that are available, including the strict clock, local clocks, discrete clocks and relaxed clocks. Techniques for calibration and clock-model selection are also described, along with methods for handling multilocus data sets. We conclude our review with some comments about the future of molecular clocks.",
    url = "https://doi.org/10.1111/mec.12953",
    doi = "10.1111/mec.12953",
    openalex = "W2028707635",
    references = "doi101073pnas1319091111, doi101073pnas504672, doi101111j14724669200900220x"
}

@article{doi101093molbevmsw054,
    author = "Kumar, Sudhir and Stecher, Glen and Tamura, Koichiro",
    title = "MEGA7: Molecular Evolutionary Genetics Analysis Version 7.0 for Bigger Datasets",
    year = "2016",
    journal = "Molecular Biology and Evolution",
    abstract = "We present the latest version of the Molecular Evolutionary Genetics Analysis (Mega) software, which contains many sophisticated methods and tools for phylogenomics and phylomedicine. In this major upgrade, Mega has been optimized for use on 64-bit computing systems for analyzing larger datasets. Researchers can now explore and analyze tens of thousands of sequences in Mega The new version also provides an advanced wizard for building timetrees and includes a new functionality to automatically predict gene duplication events in gene family trees. The 64-bit Mega is made available in two interfaces: graphical and command line. The graphical user interface (GUI) is a native Microsoft Windows application that can also be used on Mac OS X. The command line Mega is available as native applications for Windows, Linux, and Mac OS X. They are intended for use in high-throughput and scripted analysis. Both versions are available from www.megasoftware.net free of charge.",
    url = "https://doi.org/10.1093/molbev/msw054",
    doi = "10.1093/molbev/msw054",
    openalex = "W2311203695",
    references = "doi101073pnas1213199109, doi101093bioinformatics102189, doi101093bioinformaticsbts507, doi101093molbevmst197, doi101093molbevmsv037, doi101093nargks1219, doi101093nargkt1209, doi101093oxfordjournalsmolbeva040023, doi101093oxfordjournalsmolbeva040454, doi101186147121055113"
}

@article{doi101098rstb20160020,
    author = "Donoghue, Philip C. J. and Yang, Ziheng",
    title = "The evolution of methods for establishing evolutionary timescales",
    year = "2016",
    journal = "Philosophical Transactions of the Royal Society B Biological Sciences",
    abstract = "The fossil record is well known to be incomplete. Read literally, it provides a distorted view of the history of species divergence and extinction, because different species have different propensities to fossilize, the amount of rock fluctuates over geological timescales, as does the nature of the environments that it preserves. Even so, patterns in the fossil evidence allow us to assess the incompleteness of the fossil record. While the molecular clock can be used to extend the time estimates from fossil species to lineages not represented in the fossil record, fossils are the only source of information concerning absolute (geological) times in molecular dating analysis. We review different ways of incorporating fossil evidence in modern clock dating analyses, including node-calibrations where lineage divergence times are constrained using probability densities and tip-calibrations where fossil species at the tips of the tree are assigned dates from dated rock strata. While node-calibrations are often constructed by a crude assessment of the fossil evidence and thus involves arbitrariness, tip-calibrations may be too sensitive to the prior on divergence times or the branching process and influenced unduly affected by well-known problems of morphological character evolution, such as environmental influence on morphological phenotypes, correlation among traits, and convergent evolution in disparate species. We discuss the utility of time information from fossils in phylogeny estimation and the search for ancestors in the fossil record.This article is part of the themed issue 'Dating species divergences using rocks and clocks'.",
    url = "https://doi.org/10.1098/rstb.2016.0020",
    doi = "10.1098/rstb.2016.0020",
    openalex = "W2341028606",
    references = "doi101093molbevmsw026, doi101111pala12219"
}

@article{doi101016jygeno201711006,
    author = "Biswas, Kakali and Acharya, Debarun and Podder, Soumita and Ghosh, Tapash Chandra",
    title = "Evolutionary rate heterogeneity between multi- and single-interface hubs across human housekeeping and tissue-specific protein interaction network: Insights from proteins' and its partners' properties",
    year = "2017",
    journal = "Genomics",
    url = "https://doi.org/10.1016/j.ygeno.2017.11.006",
    doi = "10.1016/j.ygeno.2017.11.006",
    openalex = "W2774244422",
    references = "doi101016jygeno201604004"
}

@article{doi101093vevex025,
    author = "Volz, Erik and Frost, Simon D. W.",
    title = "Scalable relaxed clock phylogenetic dating",
    year = "2017",
    journal = "Virus Evolution",
    abstract = "Molecular clock models relate observed genetic diversity to calendar time, enabling estimation of times of common ancestry. Many large datasets of fast-evolving viruses are not well fitted by molecular clock models that assume a constant substitution rate through time, and more flexible relaxed clock models are required for robust inference of rates and dates. Estimation of relaxed molecular clocks using Bayesian Markov chain Monte Carlo is computationally expensive and may not scale well to large datasets. We build on recent advances in maximum likelihood and least-squares phylogenetic and molecular clock dating methods to develop a fast relaxed-clock method based on a Gamma-Poisson mixture model of substitution rates. This method estimates a distinct substitution rate for every lineage in the phylogeny while being scalable to large phylogenies. Unknown lineage sample dates can be estimated as well as unknown root position. We estimate confidence intervals for rates, dates, and tip dates using parametric and non-parametric bootstrap approaches. This method is implemented as an open-source R package, treedater.",
    url = "https://doi.org/10.1093/ve/vex025",
    doi = "10.1093/ve/vex025",
    openalex = "W2752084418",
    references = "doi101093molbevmsw026"
}

@article{doi101093molbevmsy044,
    author = "Tamura, Koichiro and Tao, Qiqing and Kumar, Sudhir",
    title = "Theoretical Foundation of the RelTime Method for Estimating Divergence Times from Variable Evolutionary Rates",
    year = "2018",
    journal = "Molecular Biology and Evolution",
    abstract = "RelTime estimates divergence times by relaxing the assumption of a strict molecular clock in a phylogeny. It shows excellent performance in estimating divergence times for both simulated and empirical molecular sequence data sets in which evolutionary rates varied extensively throughout the tree. RelTime is computationally efficient and scales well with increasing size of data sets. Until now, however, RelTime has not had a formal mathematical foundation. Here, we show that the basis of the RelTime approach is a relative rate framework (RRF) that combines comparisons of evolutionary rates in sister lineages with the principle of minimum rate change between evolutionary lineages and their respective descendants. We present analytical solutions for estimating relative lineage rates and divergence times under RRF. We also discuss the relationship of RRF with other approaches, including the Bayesian framework. We conclude that RelTime will be useful for phylogenies with branch lengths derived not only from molecular data, but also morphological and biochemical traits.",
    url = "https://doi.org/10.1093/molbev/msy044",
    doi = "10.1093/molbev/msy044",
    openalex = "W2949972517",
    references = "doi101038nature21074, doi101093molbevmsw026, doi101093sysbiosyw107"
}

@article{doi101016jplaphy202007006,
    author = "Jiang, Wenqiang and Geng, Yuepan and Liu, Yike and Chen, Shuhui and Cao, Shulin and Li, Wei and Chen, Huaigu and Ma, Dongfang and Yin, Junliang",
    title = "Genome-wide identification and characterization of SRO gene family in wheat: Molecular evolution and expression profiles during different stresses",
    year = "2020",
    journal = "Plant Physiology and Biochemistry",
    url = "https://doi.org/10.1016/j.plaphy.2020.07.006",
    doi = "10.1016/j.plaphy.2020.07.006",
    openalex = "W3043828941",
    references = "doi101007s11033020054775"
}

@article{doi101111jeb13889,
    author = "Whittle, Carrie A. and Kulkarni, Arpita and Extavour, Cassandra G.",
    title = "Evolutionary dynamics of sex‐biased genes expressed in cricket brains and gonads",
    year = "2021",
    journal = "Journal of Evolutionary Biology",
    abstract = "Sex-biased gene expression, particularly sex-biased expression in the gonad, has been linked to rates of protein sequence evolution (nonsynonymous to synonymous substitutions, dN/dS) in animals. However, in insects, sex-biased expression studies remain centred on a few holometabolous species. Moreover, other major tissue types such as the brain remain underexplored. Here, we studied sex-biased gene expression and protein evolution in a hemimetabolous insect, the cricket Gryllus bimaculatus. We generated novel male and female RNA-seq data for two sexual tissue types, the gonad and somatic reproductive system, and for two core components of the nervous system, the brain and ventral nerve cord. From a genome-wide analysis, we report several core findings. Firstly, testis-biased genes had accelerated evolution, as compared to ovary-biased and unbiased genes, which was associated with positive selection events. Secondly, although sex-biased brain genes were much less common than for the gonad, they exhibited a striking tendency for rapid protein sequence evolution, an effect that was stronger for the female than male brain. Further, some sex-biased brain genes were linked to sexual functions and mating behaviours, which we suggest may have accelerated their evolution via sexual selection. Thirdly, a tendency for narrow cross-tissue expression breadth, suggesting low pleiotropy, was observed for sex-biased brain genes, suggesting relaxed purifying selection, which we speculate may allow enhanced freedom to evolve adaptive protein functional changes. The findings of rapid evolution of testis-biased genes and male and female-biased brain genes are discussed with respect to pleiotropy, positive selection and the mating biology of this cricket.",
    url = "https://doi.org/10.1111/jeb.13889",
    doi = "10.1111/jeb.13889",
    openalex = "W3168750469",
    references = "doi101016jygeno201604004"
}

@incollection{crossrefNonethe,
    title = "The Speed of Light and Classical Physics",
    year = "None",
    booktitle = "The Curious History of Relativity",
    url = "https://doi.org/10.2307/j.ctv39x6bc.5",
    doi = "10.2307/j.ctv39x6bc.5",
    pages = "4-23"
}
