# Identification and interpretation of introgressed hominin DNA in modern human genomes

> **NIH NIH R01** · PRINCETON UNIVERSITY · 2022 · $333,659

## Abstract

Summary
Over the past decade, advances in ancient DNA (aDNA) have provided striking new insights into human
history, including conclusive proof that modern humans admixed with now extinct hominins, such as
Neandertals and Denisovans. In the last cycle of funding, we pioneered methods to identify and interpret
introgressed hominin DNA that still segregates in the genomes of modern humans. Analyses of these surviving
archaic lineages shows that admixture among hominins was common, there was both positive and negative
fitness consequences to gene flow, and introgressed sequences have functional and phenotypic effects.
Despite these insights, there are many fundamentally important questions that remain to be addressed. The
major barriers to a more comprehensive understanding of archaic hominin admixture include the need for
further development of computationally efficient methods to find introgressed sequences, their application to
more globally diverse populations, and experimental studies to delineate the molecular and functional
consequences of gene flow. We will address each of these issues in the renewal project. Specifically, in Aim 1,
we will extend and refine methods for identifying introgressed DNA sequences. Such further methodological
development is necessary to improve power, reduce false positive rates, and be computationally efficient
enough to analyze massively large sequencing data sets. In Aim 2, we will leverage our access to several
large-scale sequencing projects and apply these novel methods to whole-genome sequence data from over
100,000 geographically diverse individuals. Importantly, by specifically constructing a diverse panel of
individuals, particularly from understudied populations, we will be able to make inferences about archaic
hominin admixture not previously possible. We will also develop methods to comprehensively analyze the
population genetics characteristics of introgressed sequences and test hypotheses such as the fitness effects
of admixture, sex-biased patterns of gene flow, and admixture with unknown (or “ghost”) lineages. Finally, in
Aim 3, we will perform the first systematic and comprehensive experimental analysis of adaptively introgressed
loci using cutting-edge gene editing and functional genomics technologies. The successful completion of the
proposed project will extend our understanding of admixture events between archaic and modern humans,
provide insight into how introgression has shaped extant patterns of human genomic diversity, and facilitate the
molecular discovery and characterization of previously unknown archaic groups that have contributed to the
modern gene pool.

## Key facts

- **NIH application ID:** 10375563
- **Project number:** 5R01GM110068-07
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Joshua Michael Akey
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $333,659
- **Award type:** 5
- **Project period:** 2014-07-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10375563

## Citation

> US National Institutes of Health, RePORTER application 10375563, Identification and interpretation of introgressed hominin DNA in modern human genomes (5R01GM110068-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10375563. Licensed CC0.

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