Natural variation in Drosophila melanogaster

This work is dedicated to studying natural variation in D.
melanogaster at the DNA sequence and gene expression level. In
addition I present a new version of the DNA polymorphism analysis
program VariScan, which includes significant improvements. In
CHAPTER 1 I describe a genome scan of single nucleotide
polymorphism in two natural D. melanogaster populations (from
Africa and Europe) on the third chromosome. Together with
polymorphism data previously published for the X chromosome of the
same populations, this allows a comparative study of the
polymorphism patterns of the X chromosome and an autosome. The
frequency spectrum of mutations and the patterns of linkage
disequilibrium are investigated. The observed patterns indicate
that there is a significant difference in the behavior of the two
chromosomes, as has already been suggested by previous studies. To
uncover the reasons for this a coalescent based maximum likelihood
method is applied that incorporates the effects of demographic
history and unequal sex ratios. For the African population the
differential behavior of the chromosomes can be explained by its
demographic history and an excess of females. In Europe, a
population bottleneck and an excess of males alone cannot explain
the patterns we observe. The additional action of positive
selection in this population is proposed as a possible explanation.
In CHAPTER 2 I investigate the variation in gene expression of the
two aforementioned populations. Whole-genome microarrays are used
to study levels of expression for 88% of all known genes in eight
adult males from both populations. The observed levels of
expression variation are equal in Africa and Europe, despite the
fact that DNA sequence variation is much higher in Africa. This is
evidence for the action of stabilizing selection governing levels
of expression polymorphism. Supporting this view, genes involved in
many different functions, and are therefore on strong selective
constraint, show less variation than do genes with only few
functions. The experimental design allows the search for genes
which differ in their expression patterns between Europe and Africa
and might therefore have undergone adaptive evolution. Detected
candidates include genes putatively involved in insecticide
resistance and food choice. Surprisingly, many genes over-expressed
in Africa are involved in the formation and function of the flying
apparatus. In CHAPTER 3 I present version 2 of the program
VariScan. This program was designed to analyse patterns of DNA
sequence polymorphism on a chromosomal scale. The functionality of
the core analysis tool, the wavelet decomposition, is described. In
addition, multiple improvements to the previous version are
presented. The program now supports the “pairwise deletion” option.
This is essential for analysing data at the chromosome scale, since
such data often contains incomplete information. It is now possible
to add outgroup information, which allows the calculation of
additional statistics. Furthermore, the separate analysis of
different predefined chromosomal regions is added as an option. To
increase the user friendliness, a graphical user interface is now
included as part of the software package. Finally, VariScan is
applied to published and computer-generated data and the ability of
the wavelet-based analysis to uncover chromosomal regions with
interesting DNA polymorphism patterns is demonstrated.