2019 Theses Doctoral

Population Genetics of Mutation Load and Quantitative Traits in Humans

Simons, Yuval Benjamin

The past fifteen years have seen a revolution in human population genetics. We have gone from anecdotal genetic data from a few individuals at a few genetic loci to an avalanche of genome-wide sequencing data, from many individuals in many different human populations. These new data have opened up many new directions of research in human population genetics. In this work, I explore two such directions.
Genomic data have uncovered that recent changes in human population size have had dramatic effects of on the genomes of different human populations. These effects have raised the question of whether historic changes in population size have led to differences in the burden of deleterious mutations, or mutation load, between different human populations. In Chapter 1 of this thesis, I show that despite earlier arguments to the contrary only minor differences in load are expected and indeed observed between Africans and Europeans.
Over the past decade, genome-wide association studies (GWAS) have begun to systematically identify the genetic variants underlying heritable variation in quantitative traits. The number, frequencies and effect sizes of these variants reflect the selection, and other evolutionary processes, acting on traits. In Chapter 2, I develop a model for traits under pleiotropic, stabilizing selection, relate the model’s predictions to GWAS findings, and show that GWAS findings for height and BMI indeed follow model predictions. In Chapter 3, I develop a method to infer the distribution of selection coefficients acting on genome-wide significant associations made by GWAS.