Human population history and its interplay with natural selection
Creators: name: Siska, Veronika
Publisher: name: Apollo - University of Cambridge Repository
Year: 2019
Subjects: human genetics
population genetics
mathematical biology
computational biology
natural selection
malaria
sickle-cell disease
thalassemia
neutral variation
population continuity
population admixture
East Asia
neolithic transition
neolithic
Upper Palaeolithic
Georgia
Romania
paleoclimate
spatially explicit modelling
stochastic modeling
European genetics
East Asian genetics
ancient genetics
palaeoanthropology
biological anthropology
computer modelling
selection statistics
statistics
data analysis

description: The complex demographic changes that underlie the expansion of anatomically modern humans out of Africa have important consequences on the dynamics of natural selection and our ability to detect it. In this thesis, I aimed to refine our knowledge on human population history using ancient genomes, and then used a climate-informed, spatially explicit framework to explore the interplay between complex demographies and selection. I first analysed a high-coverage genome from Upper Palaeolithic Romania from ~37.8 kya, and demonstrated an early diversification of multiple lineages shortly after the out-of-Africa expansion (Chapter 2). I then investigated Late Upper Palaeolithic (~13.3ky old) and Mesolithic (~9.7 ky old) samples from the Caucasus and a Late Upper Palaeolithic (~13.7ky old) sample from Western Europe, and found that these two groups belong to distinct lineages that also diverged shortly after the out of Africa, ~45-60 ky ago (Chapter 3). Finally, I used East Asian samples from ~7.7ky ago to show that there has been a greater degree of genetic continuity in this region compared to Europe (Chapter 4). In the second part of my thesis, I used a climate-informed, spatially explicit demographic model that captures the out-of-Africa expansion to explore natural selection. I first investigated whether the model can represent the confounding effect of demography on selection statistics, when applied to neutral part of the genome (Chapter 5). Whilst the overlap between different selection statistics was somewhat underestimated by the model, the relationship between signals from different populations is generally well-captured. I then modelled natural selection in the same framework and investigated the spatial distribution of two genetic variants associated with a protective effect against malaria, sickle-cell anaemia and $\beta^0$ thalassemia (Chapter 6). I found that although this model can reproduce the disjoint ranges of different variants typical of the former, it is incompatible with overlapping distributions characteristic of the latter. Furthermore, our model is compatible with the inferred single origin of sickle-cell disease in most regions, but it can not reproduce the presence of this disorder in India without long-distance migrations.
description: The Gates Cambridge Trust provided the full funding for my PhD, including funding to attend conferences and workshop, and fourth-year funding. Trinity College helped financially through the External Honorary Research scholarship and travel funding. The Cambridge Philosophical Society contributed to funding in the fourth year of my PhD.