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Corbett-Detig, Russ Brendan

Although population genetics has a long history and firm theoretical basis, until recently little data was available for empirical hypothesis testing. The unprecedented growth of sequencing methodologies has transformed the discipline from data-poor and theory rich field into one virtually unlimited by the available of suitable data. In this thesis, we develop bioinformatic methods to address a variety of longstanding questions in the field of evolutionary genetics. Specifically, we use data derived from model organisms to study the evolution of inversion polymorphisms, segregation distorters and fitness epistasis. In the first chapter, we develop methods for detecting chromosomal inversions using next-generation sequencing data. Subsequently, we show that chromosomal inversions in Drosophila melanogaster are evolutionarily young, and at least one has likely achieved polymorphic frequencies via sex-ratio segregation distortion. In the third chapter, we develop a method of surveying the genome for segregation distortion in an unbiased manner, and show that segregation distortion does not contribute to hybrid male sterility in one pair of house mouse populations. Finally, we show that contrary to expectations, gene-gene interactions are widespread within species, which challenges a central paradigm of speciation research.

Reduced representation genome-sequencing approaches based on restriction digestion are enabling large-scale marker generation and facilitating genomic studies in a wide range of model and nonmodel systems. However, sampling chromosomes based on restriction digestion may introduce a bias in allele frequency estimation due to polymorphisms in restriction sites. To explore the effects of this nonrandom sampling and its sensitivity to different evolutionary parameters, we developed a coalescent-simulation framework to mimic the biased recovery of chromosomes in restriction-based short-read sequencing experiments (RADseq). We analysed simulated DNA sequence datasets and compared known values from simulations with those that would be estimated using a RADseq approach from the same samples. We compare these ‘true’ and ‘estimated’ values of commonly used summary statistics, (\pi), (\theta_w), Tajima's D and (F_{ST}). We show that loci with missing haplotypes have estimated summary statistic values that can deviate dramatically from true values and are also enriched for particular genealogical histories. These biases are sensitive to nonequilibrium demography, such as bottlenecks and population expansion. In silico digests with 102 completely sequenced Drosophila melanogaster genomes yielded results similar to our findings from coalescent simulations. Though the potential of RADseq for marker discovery and trait mapping in nonmodel systems remains undisputed, our results urge caution when applying this technique to make population genetic inferences.