I have been reading about mutational bias primarily through the work of Arlin Stoltzfus and it’s been a bit difficult to decipher so far. For some reason I cannot find a source that provides a good explanation of how the different biases work and the relevant research. If anyone can recommend a source (a review article, a book, a web site, etc.), I would appreciate it!
In this post though, I will describe what I have taken away from my readings, however, and show you what progress I have made while I haven’t been posting. Basically, mutations ain’t random!
The gist is that mutation matters. According to Stoltzfus, the thinkers behind the Modern Synthesis largely disregarded mutation as an evolutionary “force” or “pressure” – the mutation rate was simply too low to make a dent in allele frequencies like selection, drift, and migration did. Instead, the pool of variants produced by mutation was portrayed as nearly infinite – the trait needed for an adaptation was always at the ready. (This may be a bit extreme but it’s the general sentiment.) (If you want more information on this history, be sure to check out Arlin Stoltzfus’ blog series, The Curious Disconnect, at molevol.org or Sandwalk.)
Now, however, Stoltzfus argues that mutation bias is powerful enough to overpower selection (which I will talk about in a later post). Stoltzfus readily admits that mutational bias is nothing new but the concept hasn’t become popular outside of molecular biology and it has yet to enter our verbal understanding of evolution – something of which I think is crucial to the theory as I discussed before.
So what is mutation bias? The Modern Synthesis held that mutation was random and I don’t blame them – this was even before the discovery of the structure of DNA, but we now know that some mutations are more likely than others. A quick example (among many others) is transition:transversion bias.
A and G are purines, C and T are pyrimidines. A mutation from one purine to another (or pyrimidine to another pyrimidine) is called a transition, whereas a mutation from a purine to a pyrimidine (or vice versa) is called a transversion. Although I do not understand the biochemistry behind all of this, it makes intuitive sense that a transition is more likely than a transversion. In fact, Stoltzfus has calculated the transition:transversion bias to be around 3. This is particularly striking when you take into account that there are twice as many possible transversions than transitions (8 to 4).
Such a strong bias must have some evolutionary effect. My stumbling block was how did this bias matter? Mutation biases such as CpG mutability, CG/AT ratios, etc. certainly control (in some sense) the evolution of DNA sequence of a gene, but could we know how mutation bias had effected the gene’s evolution historically or predict its future? Natural selection “just-so stories” are easy to generate and imagine in our heads – could we do the same for mutation bias?
Well… yes, I think. It wasn’t until I read Stoltzfus’ 1999 paper, On the possibility of constructive neutral evolution, that mutation bias’ effect on the direction of evolution made sense. The paper uses several examples but I will just briefly focus on one.
Stoltzfus proposes that “duplicate gene retention” can be explained by non-adaptive (in this case, mutation) evolution as opposed to selection. When a gene or genome is duplicated, a significant chunk of the duplicates are actually retained (25-50% in bony fish (Stoltzfus 1999). Why? The selection hypothesis claims that because there are two copies of the same gene, one gene is allowed to diverge and evolve a novel function while the other gene retains and expresses the same phenotype and that this is adaptive. However, the hypothesis doesn’t explain how that duplicated gene managed to stay in the first place.
Stolzfus thinks that once the duplicated gene creates an “excess capacity” (2 working genes vs 1), the two genes will actually suffer mutations that reduce productivity because the other gene can pick up the slack. Productivity reduction will occur because “reducing” mutations are more likely to occur than productivity enhancement mutations. Think entropy here – there are more “faulty” combinations than “perfect” combinations. (If I misused entropy in the preceding sentence, please let me know.)
Stoltzfus also claims that these production reductions will stabilize the gene pair and can help explain the retained gene duplicates. There is some empirical evidence for his claims so don’t think this is merely a just-so story as I presented here. I will write a more in-depth analyses later on once I feel comfortable with my understanding – right now I’m just explaining the gist.
Because productivity-reduction mutations are more likely than productivity-enhancement mutations, mutation bias gives evolution a direction. Because mutation bias is probabilistic the direction isn’t determined – it just leans one way as opposed to another. As Stoltzfus opens his 2009 paper, mutation bias can be analogized to climbing a mountain with a slight leftward lean – you’re still ascending but just a little to the left.
The reason I want to discuss mutation bias in general is because I think non-adaptive evolution isn’t given enough credit and I find the work of scientists like Michael Lynch and Arlin Stoltzfus fascinating. I don’t know if these proposed models really apply to how evolution actually works or not; I just know that the models seem to make sense and do provide interesting alternatives to selection-based models. The topic is worth investigating and I intensely believe that we should always question the foundational principles of the arguably most successful scientific theory so far produced. We won’t know we’re wrong until we look.
If anyone has any suggestions on what to read regarding mutation bias (or non-adaptive evolution, in general), please let me know in the comments!
Also if you want to read some more on “constructive neutral evolution,” be sure to check out Psi Wavefunction’s commentary at Skeptic Wonder (Part I and Part II)!
Stoltzfus, A. (1999). On the Possibility of Constructive Neutral Evolution Journal of Molecular Evolution, 49 (2), 169-181 DOI: 10.1007/PL00006540
Stoltzfus A, & Yampolsky LY (2009). Climbing mount probable: mutation as a cause of nonrandomness in evolution. The Journal of heredity, 100 (5), 637-47 PMID: 19625453