Neutral mutations accumulate in every generation so a few remain forever

Post of the Month: August 2014

by

Subject:    | An experimental Darwinist hits the edge...
Date:       | 02 Aug 2014
Message-ID: | j-OdnXrY2b2MVkHOnZ2dnUVZ_qSdnZ2d@earthlink.com

>> Even though we could describe those mutations as "copying errors", they
>> are nonetheless part of my genome now; copied (mostly) faithfully
>> trillions of times into the cells in my body, notably including my sperm
>> cells.

>> What would prevent (some of) those mutations from being passed on to my
>> offspring? "Selection" is no answer, as I have successfully reproduced.
>> Statistically speaking, roughly half a parent's mutations should be
>> inherited by each child.

Remember when you asked where Ernest Major got that number 10E-08? This is where it where it comes into play. 10E-08 seems to be a pretty good estimate of the mutation rate in eukaryotes. So every individual born, hatched, whatever, has a number of mutations. Some number of these are deleterious (but NOT lethal, please remember that for later), most are neutral, and a very few might be beneficial.

Let's stick to the mutations that are neutral. Do you know how a mutation can be neutral? A moment's calculation will tell you there are 64 possible combinations of the four nucleotides (adenine, guanine, cytosine, thymine) that make the DNA triplets – each triplet codes for a particular amino acid. One triplet codes for AUG, the "start" codon, and three code for "stop" codons, so there's actually 60 triplets for 20 amino acids (AUG also codes for methionine, so line up quick for pedant points...)

This allows for some redundancy. Many amino acids will be produced by more than one triplet. Proline is an example. Proline is coded for by several DNA triplets, including GGG and GGT. So we could have a mutation in a DNA triplet, changing G to T or vice versa, and it's completely neutral.

Another way to get a neutral mutation becomes obvious when you look at the structure of enzymes. Most enzymes are pretty large proteins. The most critical region is the binding site, where the substrate attaches. A change in an amino acid there is likely to alter or even wreck the function of the enzyme – the substrate just won't be able to bind there anymore. Second, the enzyme has to have a particular shape to it. Ever hear the phrase "form follows function"? It's true with a vengeance in enzymes. The shape is determined by other "levels" of protein structure, in particular things like van der Waal's forces and disulfide bonds between amino acids that are distant from the binding site. A change here is slightly less likely to result in change or loss of function, but mutations can be serious. Sickle-cell disease is an example: the mutation is not a change at the oxygen binding site, but the molecular structure is altered such that the hemoglobin is liable to collapse if it is depleted of oxygen too rapidly, causing the erythrocyte to change shape or "sickle".

Now, neutral mutations are not "cancelled out" by the population's genome. There's a real chance that a mutation will be lost due to drift ("dumb luck" as you correctly put it). Remember – an organism might die without progeny, and even if it does reproduce, there's only a 50% chance that the mutation will be inherited by any given one of its offspring. But neutral mutations are accumulated over time. Heck, compare how long it takes to eliminate a lethal recessive allele from a population and it becomes obvious that neutral recessive mutations are just going to stick around forever.

How do they accumulate, you ask? Well, they just keep happening, over and over and over again. 10E-08, remember? How many nucleotides do you have in your genome? On average, we've all got about a dozen mutations that we're stuck with, and that doesn't even include the ones that happened in our parents, grandparents, great-grandparents etc. If you have any kids, each one will get about 6 of your mutations, and have a dozen of their own. Most are neutral, some might be deleterious, and some might be beneficial. Some might be back-mutations that actually revert an earlier mutation to its previous state.

Now, why did I say to remember the difference between deleterious and lethal? Lethal alleles are obviously a subset of deleterious alleles, but by no means are they the whole of the set. Too many people equate the two, and as we see in sickle-cell disease (and for that matter Huntington's disease, a lethal dominant disorder, although there's a complicating factor there) even a disease that can kill you will not necessarily prevent you from reproducing. "Deleterious" in the sense of population genetics really just means "reduced fertility" or "lower reproductive success". Might kill you, might not, but on average, you'll have fewer surviving progeny than someone not carrying that particular allele or pair of alleles, but probably not zero progeny.

This obviously applies to Behe's work, and I have not seen anyone bring it up yet. A mutation may very well be deleterious (the mutations in Plasmodium were apparently neutral, or nearly so) but so what? Unless it's a lethal dominant allele, it is NOT going to be removed from the population by selection in a single generation. It might persist for a very long time indeed.

And if it is a deleterious recessive allele, its very rarity will help it persist, wrt selection, at least. If it's recessive, it will not exert deleterious effects unless it is paired with another copy of the mutation – and that means it's highly unlikely to be exerting any ill-effects on the organism's reproductive success.

This is why inbreeding/incest can have consequences. It's not so much that one person might be a mutant – we're all mutants. But the more closely related you are to your mate, the more likely it is that you're carrying the SAME deleterious recessive alleles, rather than a completely different set.