The Neutral Theory: a genuinely important supplement to evolution’s “Modern Synthesis”

In my critique yesterday of Nathaniel Comfort’s take on The Selfish Gene, I forgot to mention one important supplement to evolution’s “Modern Synthesis,” though I believe a reader caught it. This is the “neutral theory” of evolution, proposed by Tomoko Ohta and Motoo Kimura in 1968 and described by Motoo Kimura in his 1983 book The Neutral Theory of Molecular Evolution. 

This theory proposes that many “substitutions” (mutations) in the DNA have no detectable effect on the fitness of the carrier.  In other words, compared to other variants at the gene (or site), they make no difference in the relative rate or replication of the gene: they are neither “selfish” nor “retiring”.  One example is a mutation in the second or third position of some three base “codons”, the triplets that code in the DNA (and trascribed RNA) for proteins.  Because there are more nucleotide triplets than amino acids in proteins (64 triplets but only 20 amino acids), some triplets are “synonymous”: coding for the same amino acid.

Here’s the genetic code from Wikibooks, showing that, given the first, second, and third nucleotide base in a codon, you can see which amino acid it codes for.  The four bases are T for Thymine (which become uracil in the mRNA transcribed), C for Cytosine, G for Guanine, and A for Adenine.

As you can see in the table, nearly every one of the 20 amino acids can be coded for by different triplets (“stop” codons are those that, when present in a DNA sequence, terminate the production of a protein by the matching RNA that gets translated to proteins).  In the first column, for example, you can see in the last four rows that all four codons that begin with “GT” will code for valine in the resulting protein. That means that whether the last base is a T, a C, a G, or an A makes no difference in what amino acid is in place in the protein.

So if there is a mutation in the DNA changing GTT to GTC, GTA, or GTG, the protein produced will be the same. This means that, nearly without exception, the “fitness” of these four different variants will be identical, and the mutational variants will neither be selected for or against.  You can see the number of “synonymous” codons: they comprise about a quarter of all mutations in genes that code for proteins. And that means that nearly a quarter of mutations in the DNA will not affect the “fitness” of the carrier.

But it could be even a larger number, as there are huge portions of the DNA that seem to have no function at all. This is called “junk DNA”, and constitutes about 90% of the DNA in our own genome. (There is important DNA that does not code for proteins but is not “junk,” such as bits of DNA that control the expression of other genes.)

You see that I’ve been talking about the sequences of DNA rather than organismal traits, although mutations in the former can affect the latter. This is why the “neutral theory of evolution” is often called the “neutral theory of molecular evolution.” And that, in turn, is because it’s easier to construct evolutionary theory using the frequencies of gene variants rather than traits.  But some differences in traits can also be neutral if they don’t affect fitness.  Some possible examples in humans based on mutations include whether or not your earlobes are attached, whether you can roll your tongue or wiggle your ears, and maybe your Landsteiner blood type (A, B, or O).

But I digress. Since 1963 there has been a tremendous amount of both theoretical and empirical work on the neutral theory and on the dynamics of neutral mutations.  As you might expect, truly neutral variants bounce around in frequency in populations because they’re neither selected for nor against. We know that neutral variants tend to be more visible in larger populations because small populations lead to loss of variation. We know the rate of evolutionary change of neutral variants: how often they arise in populations and how fast they become “fixed” in every member of a population (for a single change, these two rates are, curiously, equal).  We know that “nearly neutral” mutations with weak effects on replication can even overcome selection, and act as if they are truly neutral in small populations whether they be good or bad. (This depends on the relative size of the selection coefficient and the inverse of the population size.)

There’s a whole mathematical analysis of these things, but I won’t go into it. I just want to make three points.

First, the neutral theory is important, especially if you’re looking at the evolution of DNA sequences, which happens pretty often in evolutionary biology. But it can also play a role in some traits in which mutations cause visible differences (ear attachment or shell color and pattern in some snail species).

Second, the neutral theory is a truly novel modification of Darwinism that was proposed within our lifetime, though earlier evolutionists sometimes alluded to the possibility of neutral mutations.  The neutral theory is far more novel than other modifications that are said to help “overturn” evolutionary biology, like niche construction or plasticity.

Finally, Comfort does not mention the neutral theory in his article as a discovery that requires us to retool evolutionary theory, even though if there’s anything that seriously modifies our view of evolution, it is the neutral theory. The Selfish Gene doesn’t discuss it, either, even though the theory was already out when TSG was published. That’s probably because Dawkins’s book was a book about adaptive evolution, not nonadaptive or neutral evolution. (Dawkins does mention it in later books like The Blind Watchmaker.) Thus, when critiquing modern evolutionary theory, it is Comfort who should have mentioned what I think is the most important modification of our view of evolution in the last 65 years.