A species’ evolutionary history is influenced by both neutral and selective processes. The effects that these forces have on genetic variation depend on their relative contributions. It is therefore important to be able to disentangle them. I conducted a comprehensive population genetics analysis of DNA polymorphism in Drosophila melanogaster, based on data collected from more than 250 loci spanning the entire X chromosome.
Part of my work was dedicated to unraveling the relative roles of natural selection and demography in the recent history of a European population. First, I found evidence of a large impact of the population-size bottleneck associated with the colonization of Europe by the ancestral sub-Saharan populations. The multi-locus approach was crucial to disentangle neutral and selective forces, since theory predicts that demography has genome-wide effects, whereas selection acts only locally. Hence, I developed a coalescent-based maximum-likelihood method that estimated the population-size bottleneck to be ~4,000–16,000 years old. While this can account for most of the reduction of variation observed in the European sample, I could identify several loci and regions whose polymorphism pattern departs from the expectations under such a demographic scenario. One of these candidate regions was studied further in detail, revealing a pronounced valley of reduced nucleotide variation that is incompatible with a simple bottleneck model. Rather, this finding and the associated skew in the allelic frequency spectrum support the recent action of positive selection. Taken together, these results suggest that the European population experienced numerous episodes of natural selection to adapt to the new environment.
A second goal of my research was to investigate the evolutionary patterns of non-coding DNA and detect signatures of selective constraint. I found that in this species functional constraints limit the accumulation of nucleotide mutations and of insertion/deletions in both intergenic and intronic regions. In particular, I showed that insertions have smaller sizes and higher frequencies than deletions, supporting the hypothesis that they are selected to compensate for the loss of DNA caused by deletion bias. Analysis of a simple model of selective constraints suggests that the blocks of functional elements located in intergenic sequences are on average larger than those in introns, while the length distribution of relatively unconstrained sequences interspaced between these blocks is similar in the two non-coding regions. Consistently, sequences conserved across species (i.e., free of deletions and/or insertions) have lower variation and divergence compared to the remaining fraction of DNA, supporting the presence of evolutionary constraints in these blocks. Moreover, I show that the base composition of intergenic and intronic regions is shaped by a complex interaction of neutral and non-neutral processes. Remarkably, GC content seems to be an important determinant of genetic diversity
