A beneficial mutation

In pursuit of that mythical beast, the beneficial mutation.

I was in a brief discussion with another blogger recently about the possibility of human evolution, in light of the vanishingly small rate of beneficial mutation. Given the few million years involved, and the small population sizes, wouldn't it be simply impossible for apes to have accumulated beneficial mutations at the requisite rate to evolve into humans, which required roughly 170,000 such alterations, by one estimate? I will leave the details of that discussion there, but much turned on the probability of beneficial mutations, which I rated much higher than my friend did.

So, an interesting study popped up in Science recently that touches on this problem, and illustrates some of the concrete issues related to mutations in a natural setting.

Ciclid (sounds like "seek-lid") fish are famous in evolutionary biology for their rapid adaptation to new lakes and their diversification within existing habitats. This paper discusses a single mutation occuring in several species in Lake Malawi which borders Malawi, Mozambique, and Tanzania. The OB (orange blotch) mutation occurs in the gene Pax7, not affecting the protein sequence of the Pax7 protein product, but occuring in its control region and increasing its expression, though the authors do not give a detailed analysis of where and when this expression takes place. This increased expression allows the OB allele to be dominant over the wild-type BB allele.

Cichlids of Lake Malawi, female (left), or male (right); wild-type (top), or carrying the OB allele of Pax7 (bottom).

Pax7 is known to regulate the development of pigment cells in fish, (its human counterpart also has developmental roles, though slightly different effects). Incidentally, its cousin Pax6 is famous for an evolutionarily conserved role in eye development. So this mutation makes a great deal of sense in view of the phenotype, which is that fish get a mottled coat (bottom) due to fewer but bigger melanophores, where before they had a relatively uniform coat (top).

For females of these species, the mottling is beneficial by being quite a bit more effective camouflage than their wild-type uniform dark color, in relatively light-colored, rocky settings. For males, however, the mottling is a catastrophe, destroying their day-glo coloring and beautiful striping. They go from disco kings to blotchy wallflowers. Much of the paper is devoted to figuring out the odd genetic system which reduces the number of affected males dramatically in these species (about 20 species share this mutation), while maintaining the OB females in high proportion (though the authors don't give population numbers).

But something needs to be said about the basic mutation- it affects a gene which has dramatic effects on development, without deranging that development completely. It is almost as though the developmental genetics of this organism (as is true for many others) is pre-positioned for evolvability, involving a lot of controlling genes with complex regulation, which can be tweeked by relatively minor mutations to alter some features of the organism while the rest of the program goes on with little detriment.

This illustrates (anecdotally, at least) how beneficial mutations may be reasonably frequent. Variation exists in all populations, and living conditions are changing all the time. So while most changes are detrimental versus the optimized mean of the ecological landscape, conditions favor change in many edge cases and novel conditions, creating room for novel phenotypes to take advantage. Ecological landscapes are also a great deal more ragged and chaotic than the smooth abstract surfaces often used to illustrate them. I see this frequently in daily life, where some disruption to my well-honed routine first makes me upset, but then reveals a new way of doing things that I adopt as a new routine. A beneficial mutation has occurred and been selected for, which happens with some regularity.

Getting back to the fish, our males were left with a serious problem- how to minimize their embarrassment while providing the females with these beneficial OB blotches? The evolutionary solution turns out to be to link the Pax7 OB allele with the female version of a novel sex determining locus (W), so that the mutation is tightly linked to the female W, and thus happens only in female fish. Remember that not all species use the X/Y chromosome system of sex determination, indeed there are a dizzying array of such systems.

Thus not only was the OB mutation beneficial, but it was beneficial enough to overcome the harm it does to males, and to induce the resolution of that harm by linking OB with the female W determiner- a gene which the authors claim is yet another beneficial mutation (or transposition, or novel gene) that arose after the OB mutation, over-riding the locus that determines gender in other species of cichlids in the region and resides on another chromosome. Indeed, it might be beneficial enough to switch the sex chromosomes of the species (or incipient species) with OB from the previous #5 chromosome to this new location, #3, illustrating how sex determination mechanisms can shift over time.

Such hugely beneficial mutations will be rare, but based on these observations of genomic, developmental, and ecologic plasticity, I'd suggest that beneficial mutations of more modest effect are more common than the vanishingly small rates that were assumed in the analysis cited above.

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