Adaptation driven by novel mutations or from selection on standing genetic variation?

Our collegue Hopi Hoekstra at Harvard University in the US, who visited us in August last year, has a paper in one of the last issues of Science. You can read a brief report on the website Science Daily here.

At first I was not very excited about this paper, as it appears to be the usual story about the melanocortin receptor (MC1R) and how it affects coat colour patterns in various mice populations, a story that by know is sufficiently wellknown and established so one wonders what remains to be discovered.

MC1R is responsible for dark coat colour in mice that occur in dark habitats (see above), e. g. on the dark lava flows in Arizona, that Hopi Hoekstra has previously studied together with her colleague Michael Nachmann.

However, this new paper has a new twist: it appears as if selection has acted on a novel mutant in deer mice in Nebraska, and this novel that apparently appeared in the population shortly after the last Ice Age, about 8 000 years ago.

Catherine Linnen and Hopi have analyzed genetic variation among these different mice populations and estimated the age of the allele that causes light coat colour in the mice. Light coloured mice carry a certain allele at a gene called Agouti, and this allele is quite young as it shows evidence of a selective sweep through reduction in DNA sequence diversity around that particular allele. Linnen and Hoekstra have thus used the well-known statistical approach of coalescense analysis to infer the age of the novel mutation at the Agouti locus that is causing light coat colour.

This result is important, as it provides some contrast to recent suggestions that novel mutations might not be that important in cases of rapid evolutionary change, which have instead emphasize selection on standing genetic variation in rapid evolutionary change. For instance, rapid evolutionary change need not always to rely on standing genetic variation as suggested by the findings from other systems like sticklebacks. The alternative is instead that rapid adaptive change is driven by a process by which selection in novel environments "picks up" and favours alleles that already segregated in the ancestral population, rather than "waiting" for the emergence of rare novel beneficial mutations (that might take long time to appear).

This process is sometimes also called phenotype sorting, referring to how a polymorphic and variable base populations might become transformed in to a new (monomorphic and less variable) population through the selective increase and selective loss of already existing phenotypes, which are then "filtered" by selection in the novel environment. Something along these lines appears to also be the case in the freshwater isopods that we have studied in our group, and we discussed this earlier this year in a paper published in Journal of Evolutionary Biology, which you can find here.

In summary, the relative importance of selection acting on novel mutations vs. standing genetic variation is probably something that will be discussed a lot the coming years in evolutionary biology and ecology.

More reflections about quantiative genetics from Norway

I am currently in Oslo (Norway) at "Centre for Ecological Synthesis and Evolutinary Synthesis" (CEES) where I have been visiting theoretical evolutionary biologist Thomas F. Hansen. Also visiting here are evolutionary geneticists David Houle and Gunter P. Wagner. So it has been an interesting group of people to discuss, as you understand.

I talked to David Houle about the paradox that the molecular markers explain only a tiny fraction of total genetic variation in human height (see my previous bloggpost), whereas classical quantitative genetic studies (based on covariances between relatives) indicate that the real amount of genetic variation is substantially higher (between 80 and 90 %). David Houle interpreted this discrepancy very much as I did: it provides support for the so-called "infinitisemal model" in quantitative genetics, as formulated (among others) by Russel Lande.

In other words, many loci, perhaps the vast majority of all coding genes, influence human height, but each has a very small contribution in terms of percentages. This is not surprising as many independent genetic factors are likely to influence "condition" or growth, each giving a very small contribution. This makes the prospects for molecular genetic association studies quite bleach, since this approach can only (because of statistical power issues) only detect those few factors that have a relatively large effect. We are left with a situation where quantitative genetic approaches "capture" more of the existing variation than do molecular association studies that fail to detect all these small genetic factors.

This also means that we should perhaps be aware of the fact that many beatiful genetic association studies and studies of candidate genes such as the melanocortin receptor (MC1R) studied by Hopi Hoekstra's laboratory might be untypical and not representative for the vast majority of quantitative traits governed by many different genes (height being one of them). This is not surprising to me, however, it also shows that there is a lot of interesting work remaining to be done and a lot of theoretical and empirical challenges ahead.