Aaron Pfennig

School of Biological Sciences

Georgia Institute of Technology

Theoretical and empirical population genetics of admixture and introgression

Friday, September 2, 2022

11:00 am Eastern Time

EBB Krone - Children's Healthcare of Atlanta Seminar Room (room #1005)

Zoom Link: https://gatech.zoom.us/j/97879627092

Thesis Advisor:

Dr. Joseph Lachance

School of Biological Sciences

Georgia Institute of Technology

Committee Members:

Dr. Annalise Paaby

School of Biological Sciences

Georgia Institute of Technology

Dr. Patrick McGrath

School of Biological Sciences

Georgia Institute of Technology

Dr. I. King Jordan

School of Biological Sciences

Georgia Institute of Technology

Summary:

Admixture and introgression are central components of human evolution. Large-scale

movements of people have allowed gene flow between previously isolated extant populations,

creating admixed populations (e.g., African-Americans). In addition, historically anatomically

modern humans interbred with archaic hominins on multiple occasions, i.e., with Neanderthals

and Denisovans. For these reasons, admixture and introgression are crucial sources of human

genetic variation. Thus, improving our understanding of the role and implications of admixture

and introgression during human evolution will be invaluable to human health in the era of

precision medicine.

In the first part of this thesis proposal, I aim to explore population genetics models for estimating

magnitudes of sex-biased admixture from X chromosomal and autosomal ancestry proportions. I

evaluate their robustness to noisy data and violations of demographic assumptions using a

sensitivity analysis and forward simulations. Knowing the confounding effects of population

structure will help to improve the interpretability of such models. To further improve the

interpretability of such models, I also describe an approach for obtaining confidence intervals for

sex bias estimates.

In the second part, I propose a theoretical population genetics model that accounts for fitness

effects that can arise from the heterogeneous background in hybrid genomes. I aim to examine

the impact of such fitness effects on the evolutionary dynamics of an unlinked introgressed

marker allele. Specifically, I derive expressions for the fixation probability of an introgressed

allele using diffusion approximations and branching processes.

Lastly, I propose to study the legacy of archaic introgression in African Americans. A s

Neanderthal interbreeding occurred in Eurasia, many archaic alleles were only recently

(re-)exposed to human-specific alleles in genomes of African-Americans, allowing us to study

the dynamics in real-time. Therefore, studying introgressed DNA in African-American genomes

allows testing whether archaic variants are still selected against and what their phenotypic

effects are in African-Americans, among others.