Analyses of adaptive evolution and recombination rate variation in Drosophila

The neutral theory of molecular evolution provides a framework to understand the molecular basis of evolutionary change. The fundamental principle of the neutral theory is that the majority of mutations observed within populations as well as between species is neutral. More importantly, the theoretical framework that the neutral theory provides not only includes mutation and random genetic drift but also two other important parameters in evolution: selection and recombination. Molecular evolutionary analyses allow us to estimate the magnitude and consequences of these parameters in natural populations. The work presented in this thesis investigates two aspects affecting evolutionary change: adaptation and recombination.

In the second and third chapter, adaptive changes associated with a new habitat are investigated in Drosophila santomea, a species which belongs to the melanogaster subgroup and which is endemic to the volcanic island of São Tomé. In its present habitat, D. santomea inhabits a colder, darker and more humid environment compared with its sister species, Drosophila yakuba, which is distributed throughout sub-Saharan Africa. Comparisons of genome wide changes in expression between these species indicate that a group of genes involved in detection of external stimuli could be providing selective advantages to D. santomea in its new environment. In the second chapter, the coding sequences of these genes were obtained in D. santomea and analyzed to assess signatures of selection at the level of amino acid sequence. The analysis reveals that along with changes in the gene expression, protein coding sequences are evolving at a faster rate in D. santomea when compared with D. yakuba, likely providing evidence for an adaptive advantage to D. santomea when colonizing its new environment. The third chapter describes the study of the effect of cold temperature on the fitness of both species. The results indicate that D. santomea tolerates cold temperature better than D. yakuba, with different stages of the life cycle showing more pronounced effects. The observed reduction in fitness at low temperatures strongly supports the hypothesis that temperature is a key factor delimiting the distribution of these two species in their current habitats.

Recombination is an important evolutionary parameter that influences the amount of variation present within a species and the potential to adapt to biotic/abiotic changes. As such, it is a key parameter in population genetics models of selection. To date, however, no study has been able to measure the variation in recombination with high resolution (ideally at the level of single genes) while also capturing variation in recombination rates within a species. Further, there is a need to understand how the two outcomes of meiotic recombination (cross-over and gene conversion) are distributed across genomes. The fourth chapter describes the direct measurement of ultra-high-resolution variation in recombination rate throughout the D. melanogaster genome by massively genotyping the products of 5860 female meiosis. These maps reveal that cross-over rates are sharply reduced near telomeres and centromeres, with no cross-over activity in the small fourth chromosome. Importantly, we detect genomic regions with almost undetectable cross-over events embedded in large regions with high cross-over rates. Gene conversion rates are more uniformly distributed across the genome than cross-over rates and detectable even in regions with no evidence of cross-over activity. Finally, the study of intraspecific variation on cross-over rates reveals many regions with significant excess of variation thus uncovering the presence of modifiers of recombination segregating with D. melanogaster. The results from this analysis underscore the need to incorporate both intraspecific variation in cross-over rates as well as gene conversion rates into a new generation of population genetics models.