Tuesday, September 30, 2025 9/30/2025

On differentiating selective and neutral evolutionary processes

Award Number: R35GM139383
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: 02/01/2021
PERIOD OF PERFORMANCE END DATE: 08/31/2029

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On differentiating selective and neutral evolutionary processes - Jensen, Abstract At the founding of population genetics in the early 20th century, S. Wright and R.A. Fisher developed much of the mathematical framework underlying the study of population-level processes dictating variation observed within- and between-species. However, as evidenced by decades of published interactions, they held strongly differing views regarding the relative importance of adaptive vs. non-adaptive processes in driving evolution. As pointed out by J. Crow (2008), these issues were not really resolved, but rather they were abandoned in favor of more tractable studies. With the proposal of the Neutral Theory by M. Kimura and T. Ohta, the relative contribution of stochastic effects, as earlier advocated by S. Wright, received renewed attention. In the following decades, further theoretical development as well as the availability of large-scale sequencing data have indeed overwhelmingly justified the important role of genetic drift. However, subsequent research related to linked, rather than direct, selection effects have re-ignited previous debates. The primary difficulty in addressing this question has historically stemmed from our lack of an appropriate evolutionary baseline model - that is, a model jointly incorporating constantly and commonly acting evolutionary processes. This would necessarily include genetic drift as modulated by a realistic demographic history, as well as a realistic distribution of fitness effects summarizing the pervasive effects of both direct and linked purifying selection. Without this baseline model incorporating these evolutionary processes that are certain to be occurring, it is simply not feasible to accurately quantify the episodic frequency with which rarer processes (e.g., positive and balancing selection) may be further acting to shape patterns of polymorphism and divergence. During our current funding period, we have addressed this decades old limitation by developing population genetic theory and methodology to jointly estimate the parameters underlying such a baseline model, and we have applied these developments to a number of critical species (including humans, genetic model systems such as Drosophila melanogaster, and critical pathogens including influenza A virus and SARS-CoV- 2). These developments have been made in parallel for organisms well fit by Kingman coalescent assumptions (e.g., mammals) as well as those with highly skewed progeny distributions which necessitate a more generalized multiple-merger coalescent framework (e.g., viruses). In this renewal, I propose to build upon this baseline modeling to additionally infer, identify, and estimate the genomic contributions of the episodic processes of positive and balancing selection, and to extend our evolutionary baseline inference across the primate clade.


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: 2025 ( Subtotal = $1,942,326 )
2025	2025	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	003	6	8/26/2025	COMPETING CONTINUATION	$1,768,213
2025	2025	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	001	5	4/7/2025	NON-COMPETING CONTINUATION	$298,479
2025	2025	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	002	5	8/26/2025	NON-COMPETING CONTINUATION	-$124,366
2025	2024	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	000	4	11/13/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $1,942,326

Issue Date FY: 2024 ( Subtotal = $298,479 )
2024	2024	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	000	4	1/18/2024	NON-COMPETING CONTINUATION	$268,632
2024	2024	ARIZONA STATE UNIVERSITY	660 S MILL AVENUE STE 204	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	001	4	6/24/2024	NON-COMPETING CONTINUATION	$29,847
														Subtotal = $298,479

Issue Date FY: 2023 ( Subtotal = $298,479 )
2023	2023	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	000	3	1/26/2023	NON-COMPETING CONTINUATION	$268,632
2023	2023	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	001	3	3/21/2023	NON-COMPETING CONTINUATION	$29,847
														Subtotal = $298,479

Issue Date FY: 2022 ( Subtotal = $298,479 )
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	001	2	7/14/2022	NON-COMPETING CONTINUATION	$29,848
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	000	2	1/10/2022	NON-COMPETING CONTINUATION	$268,631
														Subtotal = $298,479

Issue Date FY: 2021 ( Subtotal = $206,698 )
2021	2021	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Biomedical Research and Research Training	000	1	1/28/2021	NEW	$206,698
														Subtotal = $206,698

Grand Total All Awards = $3,044,461

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On differentiating selective and neutral evolutionary processes

Award Number: R35GM139383

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: 02/01/2021

PERIOD OF PERFORMANCE END DATE: 08/31/2029

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