The selective and demographic history of Drosophila melanogaster

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.