Genetic inference of deep hominin evolutionary history using the sequentially Markovian coalescent

Whole genome sequencing has allowed researchers to infer human demographic history with unprecedented resolution. Of particular interest are the series of population size changes, admixture events, and adaptations that have occurred over time. Many methods that infer these quantities rely on differences in the distribution of genetic variants between populations, and are thus limited in scope to events more recent than when humans began to differentiate into subpopulations around 200,000 years ago (ka). Additionally, the space of possible demographic histories is large and as such all methods will make simplifying assumptions. In particular, when inferring population size histories there is frequently an assumption of indefinite panmixia which stipulates no admixture with divergent populations; conversely, methods to infer ancestral admixture typically make coarse assumptions about population size and often require sequence data from more than one population. In this thesis, I introduce a new method, cobraa, that jointly infers population size history and ancient admixture using a single diploid sequence. I demonstrate that panmictic and structured ancestries can be distinguished using the joint distribution of neighbouring coalescence times, even if their marginal coalescence time distributions are identical. The method also allows posterior estimates of local ancestry, in that we can infer which ancestral population a genomic region descends from. When applied to real data, cobraa suggests an extended period of structure in the history of all modern humans, in which two ancestral populations A and B that diverged ∼1.5 million years ago (Ma) came together in an admixture event ∼300ka, in a ratio of ∼80:20 percent. Finally, I propose that modern human sequences do not fully coalesce until beyond 10Ma, and that inference is relatively robust up until this period. I show that the data is consistent with a complex speciation between humans and chimpanzees, due to shared characteristics in these species' inverse coalescence rate trajectory around ∼5Ma.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2024

Author dc:creator

• Cousins, Trevor

Advisors dc:contributor.advisor

• Durbin, Richard
• Scally, Aylwyn

• genetics
• humans
• coalescence
• SMC
• probabilistic modelling in genomics

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/9cbc1e0e-03a0-43aa-816f-f568f49932a7/download
• http://purl.org/NET/rdflicense/allrightsreserved

Author Identifier

0000-0002-0428-9345

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/384467