Person: Nicolaisen, Lauren Elisabeth
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Nicolaisen
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Lauren Elisabeth
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Nicolaisen, Lauren Elisabeth
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Publication Distortions in Genealogies due to Purifying Selection(2014-06-06) Nicolaisen, Lauren Elisabeth; Desai, Michael Manish; Nelson, David; Wakeley, JohnAs deleterious variants continually arise in a population, they tend to be purged via purifying selection, leading to distortions in the shapes of genealogies relative to neutral expectations. In recent years, a mounting body of evidence has arisen suggesting that this can have significant implications for the patterns of diversity seen in natural populations. However, existing theory has not yet fully characterized the effects of these distortions on the structure of genealogies. The focus of this thesis is on exploring this gap, and developing an analytical description of the distortions that arise in genealogies due to purifying selection.Publication The Structure of Allelic Diversity in the Presence of Purifying Selection(Elsevier, 2012) Desai, Michael; Nicolaisen, Lauren Elisabeth; Walczak, Aleksandra M.; Plotkin, Joshua B.In the absence of selection, the structure of equilibrium allelic diversity is described by the elegant sampling formula of Ewens. This formula has helped shape our expectations of empirical patterns of molecular variation. Along with coalescent theory, it provides statistical techniques for rejecting the null model of neutrality. However, we still do not fully understand the statistics of the allelic diversity expected in the presence of natural selection. Earlier work has described the effects of strongly deleterious mutations linked to many neutral sites, and allelic variation in models where offspring fitness is unrelated to parental fitness, but it has proven difficult to understand allelic diversity in the presence of purifying selection at many linked sites. Here, we study the population genetics of infinitely many perfectly linked sites, some neutral and some deleterious. Our approach is based on studying the lineage structure within each class of individuals of similar fitness in the deleterious mutation-selection balance. Consistent with previous observations, we find that for moderate and weak selection pressures, the patterns of allelic diversity cannot be described by a neutral model for any choice of the effective population site. We compute precisely how purifying selection at many linked sites distorts the patterns of allelic diversity, by developing expressions for the likelihood of any configuration of allelic types in a sample analogous to the Ewens sampling formula.Publication The Structure of Genealogies in the Presence of Purifying Selection: a "Fitness-Class Coalescent"(Genetics Society of America, 2012) Walczak, Aleksandra M.; Nicolaisen, Lauren Elisabeth; Plotkin, Joshua B.; Desai, MichaelCompared to a neutral model, purifying selection distorts the structure of genealogies and hence alters the patterns of sampled genetic variation. Although these distortions may be common in nature, our understanding of how we expect purifying selection to affect patterns of molecular variation remains incomplete. Genealogical approaches such as coalescent theory have proven difficult to generalize to situations involving selection at many linked sites, unless selection pressures are extremely strong. Here, we introduce an effective coalescent theory (a "fitness-class coalescent") to describe the structure of genealogies in the presence of purifying selection at many linked sites. We use this effective theory to calculate several simple statistics describing the expected patterns of variation in sequence data, both at the sites under selection and at linked neutral sites. Our analysis combines a description of the allele frequency spectrum in the presence of purifying selection with the structured coalescent approach of Kaplan et al. (1988), to trace the ancestry of individuals through the distribution of fitnesses within the population. We also derive our results using a more direct extension of the structured coalescent approach of Hudson and Kaplan (1994). We find that purifying selection leads to patterns of genetic variation that are related but not identical to a neutrally evolving population in which population size has varied in a specific way in the past.