Studying Human Evolution. In Mice.

The evolutionary history of humanity isn’t the easiest tale to tell. As time passed, we, unlike other primates, spread across the globe, colonizing the various lands we explored. All these different habitats were surely characterized by diverging sets of selection pressures. Lo and behold, there arose diversity among human beings. But finding the exact genetic basis of said diversity has proven a difficult task.

Enter modern science and technology.

With data of the 1000 Genome Project at their disposal, researchers have identified regions of the human genome that show signs of fairly recent (in evolutionary terms, of course) selection. Further analysis of these signals, recently published in the prestigious journal Cell, resulted in a list of 94 gene variants that are likely to be involved in recent adaptations.

A follow-up study, also in Cell, focused on one of the strongest candidates, known as EDAR370A, a variant of a gene that’s known to affect hair thickness and tooth shape. To study the potential adaptive role of the variants, the researchers developed a mouse model in which the 370A variant would be expressed.

These mice developed:

• Thicker hair.

• Alterations in mammary gland branching and decreased fat pad size.

• More eccrine sweat glands.

But what about human beings? After all, there are still difference between mice and humans, something the authors are well aware off.

(Indeed, another recent study questions the use of mice as disease models. Of course, there are many different strains of ‘humanized’ mice used in research, so some might be better suited for certain investigations than other. And the studies I’m discussing here don’t really involve diseases, but perhaps the question extends to animal models in evolutionary studies?)

Fortunately, the scientists didn’t stop there. They found that the 370A variant under scrutiny arose and is far more common in central China. Off to China, then, where they sampled 623 people of Han descent. And, as expected, the results showed an influence of the variant on teeth shape and the number of eccrine sweat glands.

Graphical summary of the research. (from Cell)

With regards to the adaptive potential, the authors offer some thoughts:

• More sweat glands allow for more transpiration, pretty useful for vigorous activity in humid environs.

• Alterations of the mammary glands (not assessed in humans) might influence lactation, quite important for the kids.

• The pleiotropic nature of the gene variant (it affects several traits) might mean that one or more selection pressures operated on all these traits simultaneously.

In the words of the authors:

Consequently, the cumulative selective force acting over time on diverse traits caused by a single pleiotropic mutation could have driven the rise and spread of 370A.

And now, I’ll let some of the authors do the talking.

(The gist: they selected a gene variant that could’ve been important in human evolution, made mice that expressed it, watched what happened and went to check it in people carrying the variant. Cool, huh?)

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Grossman, S., Andersen, K., Shlyakhter, I., Tabrizi, S., Winnicki, S., Yen, A., Park, D., Griesemer, D., Karlsson, E., Wong, S., Cabili, M., Adegbola, R., Bamezai, R., Hill, A., Vannberg, F., Rinn, J., Lander, E., Schaffner, S., & Sabeti, P. (2013). Identifying Recent Adaptations in Large-Scale Genomic Data Cell, 152 (4), 703-713 DOI: 10.1016/j.cell.2013.01.035

Kamberov, Y., Wang, S., Tan, J., Gerbault, P., Wark, A., Tan, L., Yang, Y., Li, S., Tang, K., Chen, H., Powell, A., Itan, Y., Fuller, D., Lohmueller, J., Mao, J., Schachar, A., Paymer, M., Hostetter, E., Byrne, E., Burnett, M., McMahon, A., Thomas, M., Lieberman, D., Jin, L., Tabin, C., Morgan, B., & Sabeti, P. (2013). Modeling Recent Human Evolution in Mice by Expression of a Selected EDAR Variant Cell, 152 (4), 691-702 DOI: 10.1016/j.cell.2013.01.016

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