William DeWitt1,2, Kameron Decker-Harris1, Kelley Harris1,2
1) University of Washington, Seattle; 2) Fred Hutchinson Cancer Research Center, Seattle.
Models in evolutionary genetics typically assume that mutation rate is constant over time and between populations and closely related species. However, recent work casts doubt on this assumption in human and ape populations, and reveals that mutation is a complex and dynamic process. Whether arising from variation in replication fidelity, life history, or environmental exposures, mutation rate evolution can be accompanied by changes to the mutation spectrum: the mutation rate in different local nucleotide contexts. We extend theoretical tools based on Kingman’s coalescent to accommodate a richly parameterized mutation process, varying in time and in spectrum. We infer human mutation spectrum histories from patterns of modern genomic diversity, allowing us to reconstruct trajectories of mutation spectrum divergence between populations, track a transient mutation spectrum perturbation through multiple populations, and characterize how mutation spectrum histories are structured by local nucleotide context. Mutation rate and effective population size together determine the strength of genetic drift shaping genomic variation. We introduce fast nonparametric joint inference of mutation spectrum history and demographic history from unphased genomes.
Inferring the Demographic History of Inbred Species from Genome-Wide SNP Frequency Data (1238B)
Demographic inference using the site frequency spectrum (SFS) is a common way to understand historical events affecting genetic variation. However, most methods for estimating demography from the SFS assume random mating within populations, precluding these types of analyses in inbred populations. To address this issue, we developed a model for the expected SFS that includes inbreeding by parameterizing individual genotypes using beta-binomial distributions and taking their convolution to calculate the probability of sampling biallelic variants with different population frequencies. Using simulations, we evaluated the model’s ability to co-estimate demography and inbreeding using one- and two-population models across a range of inbreeding levels. We also applied our method to two empirical examples, American pumas (Puma concolor) and domesticated cabbage (Brassica oleracea L.), inferring models both with and without inbreeding to compare parameter estimates and model fit. Our simulations showed that we were able to accurately co-estimate demographic parameters and inbreeding even for highly inbred populations (F=0.9). In contrast, failing to include inbreeding generally resulted in inaccurate parameter estimates in simulated data and led to poor model fit in our empirical analyses. These results show that inbreeding can have a strong effect on demographic inference, a pattern that was especially noticeable for parameters involving changes in population size. Given the importance of these estimates for informing practices in conservation, agriculture, and elsewhere, our method provides an important advancement for accurately estimating the demographic histories of these species.
Determining the risk of hemiplasy in the presence of incomplete lineage sorting and introgression (1295B)
The incongruence of character states with phylogenetic relationships is often interpreted as evidence of convergent evolution. However, trait evolution along discordant gene trees can also generate these incongruences – a phenomenon known as hemiplasy. Classic phylogenetic comparative methods do not account for discordance, resulting in incorrect inferences about the number of times a trait has evolved, and therefore about convergence. Biological sources of discordance include incomplete lineage sorting (ILS) and introgression, but only ILS has received theoretical consideration in the context of hemiplasy. Here, we derive expectations for the probabilities of hemiplasy and homoplasy with ILS and introgression acting simultaneously. We find that introgression always makes hemiplasy more likely, suggesting that methods that account for discordance due to ILS alone will be conservative. We also present a method for making statistical inferences about the relative probabilities of hemiplasy and homoplasy in empirical datasets. Our method is packaged in software dubbed HeIST (Hemiplasy Inference Simulation Tool), and provides information on the most probable number of transitions among character states given a set of relationships with discordance. HeIST can accommodate ILS and introgression simultaneously, and can be applied to large phylogenies. We apply this tool to a phylogeny of New Guinea lizards that have evolved green blood from a red-blooded ancestor, and find that hemiplasy is likely to explain the observed trait incongruence.
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