Population genetics of human evolutionary history and natural selection

Active Project Grant Awarded Last action

Award ID
R35GM154962
Recipient
Awarding agency
Obligated
$1,501,720

Award facts

Assistance listing
93.859 Biomedical Research and Research Training
Completion date 46% complete
Place of performance
Madison, WI 53715, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
This proposed research addresses unresolved and fundamental questions in human evolutionary history and the formation of genetic diversity. IT contains three related research themes: (1) uncovering key features of human population history and structure, both in the recent and ancient past, (2) determining factors influencing selection across the genome and the limits to cross-population phenotypic prediction due to population history and natural selection, and (3) modeling and predicting the genetic basis of complex traits under realistic models of human evolutionary history, population structure and admixture. This work combines ambitious but feasible methodological developments with new data from diverse worldwide populations. Human evolutionary history is imprinted in the DNA of people living today. Learning this history involves the combined efforts of theoretical, statistical, and empirical analyses. As the volume of genome sequencing data grows, we have the opportunity to infer new details from key periods in our species' evolution and clarify how population biology and natural selection shape phenotypic and genetic variation. This requires developing population genetic theory and computational methods that can handle data from many populations and large sample sizes, and that simultaneously incorporate these many different factors that impact genetic diversity. Over the next five years, my group will develop theoretical and methodological innovations that enable new discoveries from human population genomic data, and we will uncover details of human history that resolve important questions about our species' evolution. This work builds on my lab's expertise in population genetic theory and simulation methods. Recent work shows that our newly developed approaches for modeling diversity and linkage disequilibrium statistics are powerful to learn complex multi-population history. Combined with newly sequenced high-quality genomic data, we will unravel early human evolution and reconstruct recent admixture and demographic histories of latin american populations. These models build genomic resources for understudied populations and are essential to downstream studies to understand genetic components of health and disease susceptibility. Our theoretical advances will enable new analyses of the combined effects of selection and recombination in multiple populations, which we will use to understand fundamental limits to the portability of phenotypic prediction across populations and in recently admixed groups. Finally, we will develop approaches to predict the architecture of polygenic traits in structured and admixed populations, settings that are most relevant for human genomic studies, but current methods fail to address. The mathematical and statistical advances from this work will be developed into open source, maintained computational resources that will facilitate genomic discoveries in our own research and that of others in the years to come.

Transactions

Action Obligated Date
Amendment $375,430
Amendment $375,430
Amendment $375,430
Original award $375,430

Quick answers

Who received award R35GM154962?

R35GM154962 was awarded to University Of Wisconsin System by National Institute of General Medical Sciences (National Institutes of Health) on August 1, 2024.

How much is award R35GM154962 worth?

$1,501,720 has been obligated on R35GM154962.

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