Comparative analysis of derived mutations across human populations

Thesis

Multiple factors, including the rate of mutation of different types, the action of natural selection, recombination and population history all influence the distribution of genetic variation within and between populations. Here, we seek to explore the relative contributions of different factors to notable aspects of the derived site frequency spectrum in different populations from the 1000 Genomes Project. Specifically, we ask whether individuals from different populations carry different numbers of mutations (indicative of differences in the mutation rate or average generation time of populations) and whether patterns differ between types of mutation in different sequence contexts. Our results indicate that the average mutation rate (per year) in African populations has been slightly, but significantly, higher than in non-African populations which has led to an enrichment in the number of derived alleles harbored in African populations. In a departure from the literature, we find that the non-synonymous mutation load does not vary between populations. We present weak evidence for differential mutational processes at CpG sites in African individuals and estimate a TMRCA of the human population as approximately 3.5 mya. Last, we suggest ways in which our knowledge of derived alleles can allow us to make improvements to existing population genetic methods, such as the sequentially Markov coalescent.

Authors: Feder, AF

• Publication date: 2013
• DOI: 10.5287/ora-yebdm4bkv
• Type of award: MSc by Research
• Level of award: Masters
• Awarding institution: University of Oxford
• Language: English
• Keywords: human population genetics
• Subjects: Mathematical genetics and bioinformatics (statistics)