Evolution and diversity of hominid genomes

Abstract

Copy number variants (CNVs) contribute to a substantial amount of diversity both between and among hominid species. In this thesis I set out to catalog this variation across the hominid lineage and assess its impact on the evolution of great ape species and its contribution to extant diversity. I develop methods to detect and genotype CNVs using high-throughput sequencing and demonstrate the first population scale analysis of the diversity of segmental duplications and duplicated gene families in a panel of 159 humans. I identify 56 highly population stratified genes and 23 genes that have undergone duplication specifically in the human lineage. I go on to demonstrate a resource of 4.1 million singly unique nucleotide (SUN) identifiers, which can be used to infer paralog-specific copy number and explore duplicated gene families. I next describe the sequencing of a panel of 79 wild and captive-born great apes to better understand the genetic diversity of extant great ape populations. I identify 86.5 million single nucleotide polymorphisms (SNPs) and use this resource to construct a model of great ape demography and population diversity. I outline the topology of relationships between great ape populations and the relative levels of heterozygosity among these populations. Finally, I identify 23,770 CNVs in these great ape individuals and characterize diversity both within and between species. Among these CNVs I identify the first example of a genomic disorder in a chimpanzee--a single individual with features resembling Smith-Magenis syndrome. I calculate the exact rates of duplication and deletion along each of the great ape lineages and show that an excess of deletions occurred along the chimpanzee-bonobo ancestral lineage. This excess coincides with a severe drop in the effective population size of the chimpanzee-bonobo ancestor. Analysis of recently bottlenecked great ape populations also shows an excess burden of duplications and deletions among these individuals. These results suggest that changes in effective population size may be responsible for historical shifts in the rates of duplication and deletion in the hominid lineage.