Inferring hominin population history through space and time using introgressed haplotypes

Introduction

In the last decade, ancient DNA studies have increased their throughput from single samples to thousands of genomes published every year, giving us unprecedented data about human genetic history. However, tools and methods that efficiently use this wealth of data are sorely lacking, especially because DNA extracted from fossils is often scarce and contaminated. In this project, I develop population genetic theory and bioinformatic methods that use ancient DNA to refine estimates of when and where archaic and modern humans interbred, to characterize the historical, biological, and functional consequences of this gene flow, and to learn about the differences between modern humans, Neandertals, and Denisovans.

Project Aims

Aim 1: Genotype-Likelihood Approach

The first aim of this project is to develop a robust and general genotype-likelihood approach for local ancestry inference that allows efficient use of contaminated, low-coverage data. Additionally, I will establish approximate haplotype-based methods for inferring introgression tracts.

Aim 2: Population Genetic Theory and Statistical Methods

The second aim of the project is to develop the necessary population genetic theory and statistical methods to translate the inferred haplotypes into biological insights. The proposed theoretical, numerical, and simulation-based approaches will link the inferred introgression patterns with the underlying population genetic processes.

Aim 3: Application of Novel Tools

The final aim is to apply these novel tools to study where and when gene flow between Neandertals, Denisovans, and modern humans occurred. I also aim to identify introgressed haplotypes that are a target of natural selection and to quantify the relative importance of positive, negative, and balancing selection on Neandertal and Denisovan gene flow.

Expected Outcomes

As a result, this work will expand the tool set available for the analysis of ancient DNA, reveal the precise history of the interactions of Neandertals and modern humans, and provide answers to the key question of what genetic factors contributed to the survival of our species, while all other hominins went extinct.