The role of selection and environment in shaping genetic variation in Drosophila [electronic resource]

As life evolves and generation upon generation accumulates mutations and experiences selection, the resulting genetic changes provide a record of the evolutionary dynamics. Population genetic variation, consisting of the allele frequencies of variants in a population, provides a detailed record of the contemporary dynamics of evolution. Of particular relevance here, population genetic variation can track "evolution in action" in systems where selection is occurring on spatial and rapid temporal scales. In addition, the distribution of allele frequencies (site frequency spectrum, or "SFS") can illuminate the strength of selection acting on groups of sites in the genome. While the concept of using population genetic data to study these processes is decades old, the ability to study these processes genome-wide is relatively new. Population genomic studies allow us to quantify the extent that selective processes are affecting populations, and how that differs between species. In this dissertation I utilize population genomic data to characterize patterns of selection and demography across spatial and temporal transects and to detect patterns of selection on synonymous variation. I use the model system, Drosophila melanogaster, which, in addition to having a conveniently short generation time and a small and well-annotated genome, has been studied since the 1920's as model system for understanding ecology, evolution and genetics. D. melanogaster is also one of the most well sequenced organisms. I utilize pre-existing population genomic data as well as produce a substantial amount of D. melanogaster and D. simulans genome sequence data to conduct three separate studies: 1) the comparative genomics of latitudinal genetic variation, 2) seasonal genetic variation across populations, and 3) the causes and consequences of selection on synonymous variation. In the first study, I focus on the genomic patterns of variation with latitude. Examples of clinal variation in phenotypes and genotypes across latitudinal transects have served as important models for understanding how spatially varying selection and demographic forces shape variation within species. I examine the selective and demographic contributions to latitudinal variation through the largest comparative genomic study to date of D. simulans and D. melanogaster, with genomic sequence data from 382 individual fruit flies, collected across a spatial transect of 19 degrees latitude and at multiple timepoints over two years. Consistent with phenotypic studies, I find less clinal variation in D. simulans than D. melanogaster, particularly for the autosomes. Moreover, I find that clinally varying loci in D. simulans are less stable over multiple years than comparable clines in D. melanogaster. D. simulans shows a significantly weaker pattern of isolation by distance than D. melanogaster and I find evidence for a strong contribution of annual re-migration to D. simulans population genetic structure. While population bottlenecks and migration can plausibly explain the differences in amount and stability of clinal variation between the two species, I also observe a significant enrichment of shared clinal genes, suggesting that the selective forces associated with climate are acting on the same genes and phenotypes in D. simulans and D. melanogaster. In the second study I focus on temporal variation. One large source of temporal variation is seasonal fluctuation in the environment. Seasonal environmental heterogeneity can act as a fluctuating selective pressure, which can result in the maintenance of genetic variation if there is a fitness trade-off across seasons. I use pooled population genomic sequence data for 26 populations, sampled seasonally (spring and fall), and sampled across years, to assess the extent of seasonal genetic fluctuation and the consistency of seasonal variation across geographic regions. I find that there is an excess of genetic variants that behave in the same seasonal way across geographic regions. However, this enrichment is weak, suggesting that the identity of seasonal variants shifts temporally and spatially. As seasonal changes in the environment mirror some of the changes seen along a latitudinal cline, we also test for parallelism between seasonal and clinal variants. I find a strong enrichment of sites that change in allele frequency in the same manner from the south to the north as from the fall to the spring. The global consistency, from across Europe and North America, in seasonal and latitudinal variation strongly suggests that these patterns result from selection rather than demography. Finally, I take a departure from temporal and spatial heterogeneity to look at genomic heterogeneity in selective pressures. Specifically, I assess the cause and extent of selection on synonymous sites. Strikingly, I find evidence for strong purifying selection on synonymous sites associated with biased codon usage. Although biased codon usage is a well-documented phenomenon, the extent of selection on biased codon usage was previously not well understood. Using genome sequence data from two D. melanogaster populations, I performed an SFS-based maximum likelihood estimation of purifying selection on fourfold degenerate synonymous sites using short introns as a neutral control. In addition to finding strong purifying selection on synonymous sites due to codon bias, I also find a significant positive relationship between the change in codon usage bias (ancestral to derived) and polymorphism. This is suggestive of purifying selection on derived unpreferred alleles and positive selection on derived preferred alleles. Synonymous sites in alternatively spliced genes, RNA binding protein bound regions and splice junctions are also under detectable amounts of strong purifying selection; however, codon bias explains the greatest proportion of sites under selection. My finding of strong selection on codon bias directly conflicts with previous models of codon bias that predict uniformly weak selection and indicates that the functional effect of biased codon usage has been underestimated.

Keywords: Biology.
Advisor: Petrov Dmitri Alex
Feldman Marcus W. advisor. Thesis advisor
Hadly Elizabeth Anne
Pritchard Jonathan (Jonathan K.) advisor. Thesis advisor