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Evolution on epidemiologically-relevant timescales

Award Number: R35GM133481
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2019
PERIOD OF PERFORMANCE END DATE: 04/30/2030

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Evolution on epidemiologically-relevant timescales - PROJECT SUMMARY Genetic variation encodes the history of our species, underlies our ability to adapt to new environments, and is the basis for individual- and population-specific disease risk. Over billions of years, evolution has transformed living organisms from simple single cells to the huge diversity around us. However, evolution is more than an ancient process of our past; it is ongoing. While a flash of evolutionary time, the last ~10,000 years have been a period of extraordinary genetic and phenotypic change: humans have adopted agriculture, pushed into new environments, and exploded in population size, increasing gene flow between populations and infectious disease exposure. Indeed, most human genetic variants arose in the last 10s to 100s of generations. Yet, many common population-genetic tools don’t work on this timescale. By leveraging the signatures of rapid evolution, we aim to tackle fundamental evolutionary questions such as how populations adapt to new environments and emerging diseases. Over the past 4 years since starting the lab and R35, we have developed and applied multiple new theoretical models and computational methods to understand demographic and selective processes in admixed populations. The flexibility of the R35 further allowed us to branch into two newer models systems for evolutionary genetics: pathogen evolution and primates as a model of human evolution. Over the next five years, we will tackle these questions across three timescales and model systems. Area 1: leveraging genetic ancestry to infer adaptation & phenotype evolution. We will develop new statistics to infer positive selection within the last tens of generations using admixed genomes both before and after admixture, and use ancestry patterns to test hypotheses about broader genetic architectures. Area 2: model-based inference of selection under complex pathogen lifecycles. Using our expertise in population- genetic and dynamical systems transmission models, we recently developed a model that bridges epidemiological and genetic change by synthesizing whole-genome simulations and dynamical systems models. We will extend our theoretical models of evolution in pathogen systems that incorporate realistic dynamics, starting with malaria as a case study, to understand how different aspects of the lifecycle shape neutral variation and our ability to detect adaptation. Finally, Area 3: using primates as a model of large-scale structural evolution. As our close phylogenetic relatives, primates are an ideal system to understand human evolution, and mechanisms generating genetic variation. Within mammals, large-scale structural variation and chromosome number evolution is generally one of the slower evolutionary processes with large conservation across phyla. However, multiple primates show surprisingly large karyotype evolution and structural changes during within-genus radiations. We will use a combination of population-level resequencing of wild primates with long-read technologies to study karyotype evolution, recombination variation, and the potential adaptive consequences of structural variation.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $446,119 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	7	4/27/2026	NON-COMPETING CONTINUATION	$446,119
2026	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	000	5	2/24/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $446,119

Issue Date FY: 2025 ( Subtotal = $446,119 )
2025	2025	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Biomedical Research and Research Training	001	6	6/14/2025	COMPETING CONTINUATION	$446,119
2025	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	000	5	6/13/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $446,119

Issue Date FY: 2023 ( Subtotal = $372,164 )
2023	2023	DUKE UNIVERSITY	2200 W MAIN ST	DURHAM	NC	27705	DURHAM	USA	Biomedical Research and Research Training	000	5	6/7/2023	NON-COMPETING CONTINUATION	$372,164
														Subtotal = $372,164

Issue Date FY: 2022 ( Subtotal = $372,164 )
2022	2022	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	4	6/7/2022	NON-COMPETING CONTINUATION	$372,164
														Subtotal = $372,164

Issue Date FY: 2021 ( Subtotal = $435,173 )
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	3	8/19/2021	SUPPLEMENT FOR EXPANSION	$63,009
2021	2021	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	3	7/13/2021	NON-COMPETING CONTINUATION	$372,164
														Subtotal = $435,173

Issue Date FY: 2020 ( Subtotal = $373,097 )
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	2	6/15/2020	NON-COMPETING CONTINUATION	$373,097
2020	2020	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	001	2	6/22/2020	NON-COMPETING CONTINUATION	$0
														Subtotal = $373,097

Issue Date FY: 2019 ( Subtotal = $373,097 )
2019	2019	DUKE UNIVERSITY	2200 W MAIN ST STE 710	DURHAM	NC	27708	DURHAM	USA	Biomedical Research and Research Training	000	1	8/26/2019	NEW	$373,097
														Subtotal = $373,097

Grand Total All Awards = $2,817,933

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Evolution on epidemiologically-relevant timescales

Award Number: R35GM133481

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2019

PERIOD OF PERFORMANCE END DATE: 04/30/2030

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