Population Genetic Approaches to Detect Natural Selection in Drosophila melanogaster

This thesis intends to detect evidence of Darwinian selection and
ultimately identify genes and substitutions that were involved in
adaptation. The model organism Drosophila melanogaster was chosen
as the study object, since the availability of the genome sequence
and its evolutionary history allows us to investigate ancestral and
derived populations. To identify the footprints of natural
selection, the first objective was to locate genomic regions
subject to selection. Such footprints involve a reduction in
genetic variation along a recombining chromosome caused by a
fixation of a beneficial mutation (i.e., so-called “selective
sweep”) in a population under study. Single nucleotide
polymorphisms of non-coding regions (i.e., 105 fragments) of the X
chromosome in a putatively ancestral population of D. melanogaster
from Zimbabwe were surveyed and compared to a derived European
population in the first chapter. In contrast to the European
population, evidence of selection was weak in the African
population, but a strong signature of a population size expansion
was observed. To examine the impact of demography and selection
more deeply, an analysis of an enlarged DNA sequencing data set
(i.e., 253 fragments) of the African population is presented in
chapter two. A clear signature of a recent size expansion was
observed and the time estimated of the expansion is 15,000 years
before present, which was probably caused by drastic climatic
changes. The enlarged data set revealed, in addition, that
recombination is mutagenic in D. melanogaster. In the second part
of this thesis, candidate regions of selective sweeps detected in
the genome scan in both populations of D. melanogaster were
investigated. In chapter three, a more detailed analysis of the
region comprising an observed local reduction in variation in one
X-linked fragment in the derived European population revealed
significant evidence of recent Darwinian selection. The target of
selection was attributed to three replacement sites leading to
amino acid changes in two predicted genes, CG1677 and CG2059. In
contrast, a lower number of haplotypes and a trend for low
haplotype diversity suggesting the recent action of a selective
sweep was examined in chapter four in the ancestral D. melanogaster
population. An enlarged DNA sequencing data set revealed another
feature unique to a selective sweep, namely the decay in haplotype
structure. The target of selection was localized at the 5’ region
of gene CG4661. In the third part of this thesis, the genetic
variation of D. melanogaster populations from Southeast Asia were
examined to provide first insights into these derived populations
and the groundwork for future studies. Since no population genetic
approach was done in natural D. melanogaster populations from this
region, inversions were used as genetic markers. Other than a high
frequency of the four common cosmopolitan inversions, there were
neither signs for genetic differentiation between populations nor
for natural selection. These findings can best be explained by a
homogeneous habitat and a joint history of these populations
revealing the existence of a panmictic population on Sundaland
~18,000 years ago.