Converging genes reveal how plagues have shaped our genome

Evolution is shaped by numerous factors. Selection is one of such factors, but, contrary to popular belief, it is not the only force acting on genomes. I cringe when I hear the expression "this gene has been selected for" because most of our alleles (we all have the same genes, but each gene can have different alleles across different ethnic groups/populations) haven't been selected at all. Things change even without any selection pressure from the environment, a phenomenon known as random drift. every new generation is a (more or less) random sample from the previous generation, and this constant resampling ensures a background change in allele frequencies, even without any selection pressure from the environment.

Because selection is not the only factor that shapes evolution, it is hard to look at how our genome evolved and pin point what changes were due to selection and which ones weren't. However, there are some rare situations where scientists get lucky. One such example is the Rroma people, also known as Gipsies. This ethnic group originated from Northern India and migrated to Europe around 1,000-1,500 years ago. Because throughout the centuries they remained a homogeneous group and rarely mingled with the local population, when looking back at some of the historical plagues that swept through Europe, the Rroma offer a unique snapshot of a distinct population undergoing the same selection pressure as the locals.

Here's the logic: alleles found in the Rroma population but not in their Indian ancestors must have risen recently in the Rroma population. If those alleles are also found in the local population, which are not related to the Rroma, then these alleles must have risen independently in the two populations. But how, if the two populations did not intermerry? Well, if you think about it, the part of our body that's most certainly under selection pressure is the immune system: a strong immune system enables the survival of not just one individual, but also of his/her offspring if they inherit the right alleles. Historical plagues that swept through Europe exerted a strong selection pressure on the immune system at the population level. Individuals with favorable alleles were able to survive these plagues, whereas the others succumbed. So, when the researchers found alleles that had risen independently in the Rroma and in the local population, they concluded
that they had been selected by severe epidemics in Europe.

The study, published in PNAS last week [1], aimed at finding "convergent evolution" between the two coexisting but genetically distinct populations. Convergent evolution means that, under selection pressure (such as for example a widespread epidemic), distinct genomes are forced to converge independently to the same allele because that particular allele confers protection against the epidemic.

"We hypothesized that despite their different ethnic and genetic backgrounds, the strong infectious pressure exerted by the major epidemics of the last millennium (of which epidemics of plague are probably the most significant) has led to convergent evolution: specific immune genes, selected during these European epidemics, become signatures that differ from those found in the Northwest Indian populations from whom the Rroma have derived [1]."

Laayouni et al. [1] found several gene clusters under positive selection, of which one in particular (TLR1, TLR6, and TLR10) code for receptors that modulate responses to Yersinia pestis, the bacterium responsible for the bubonic plague.

Hafid Laayounia,1, Marije Oostingb,c,1, Pierre Luisia, Mihai Ioanab,d, Santos Alonsoe, Isis Ricaño-Poncef, Gosia Trynkaf,2, Alexandra Zhernakovaf, Theo S. Plantingab, Shih-Chin Chengb, Jos W. M. van der Meerb, Radu Poppg, Ajit Soodh, B. K. Thelmai, Cisca (2014). Convergent evolution in European and Rroma populations reveals pressure exerted by plague on Toll-like receptors PNAS DOI: 10.1073/pnas.1317723111