# Jointly modeling the effects of evolutionary processes on genomic variation

> **NIH NIH R35** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2024 · $388,750

## Abstract

PROJECT SUMMARY
Understanding what shapes patterns of genetic diversity in natural populations is an inherently challenging
problem. Despite the challenges, studying variation in DNA sequences within individuals in a population has
the power to yield insights into selective pressures operating in the natural environment of a species, uncover
historical events like the migration of humans and their pathogens across the world, and identify the genetic
basis of traits like human diseases. One major challenge facing population-genomic inference is that most
current state-of-the-art approaches have been developed to study human-like genomes, that are sparsely
populated with functionally important elements and thus effects of selection on nearby sites can be ignored.
These assumptions however do not apply to compact (gene-dense) genomes where direct and indirect effects
of selection are pervasive. My research program is geared towards understanding how the joint effects of
selection with other evolutionary processes operating simultaneously in a population, shape patterns of
variation across the genome. As many pathogenic species tend to have highly compact genomes, experience
strong bouts of selection as well as drastic repeated bottlenecks, and undergo asexual reproduction or self-
fertilization often (which further increases the effects of selection), our methods would be absolutely essential
to perform inference in such species. We will employ computational, statistical, and theoretical approaches to
broach these questions, utilizing the development of new methods and their applications to publicly available
whole-genome sequence variation data.
 The strength of selection against new mutations, a crucial piece of information for modeling how
selection shapes variation, has been estimated predominantly for coding regions, despite the fact that in many
species the majority of functional DNA that impacts fitness is non-coding. My first goal will therefore be to
generate a better estimate of the shape of the genome-wide fitness effects of new mutations. As lower rates of
recombination result in stronger effects of selection, my second goal is to better understand how selection
against deleterious mutations affects genome-wide patterns of variation in species that undergo high rates of
self-fertilization and to develop methods that account for the effects of selection. My third goal is to apply our
methods to perform inference of demography and identification of recent selective sweeps in species with
compact genomes, like those of Plasmodium falciparum and vivax. My work will result in a better
understanding of how natural selection shapes genomic variation, as well as the development and application
of methods that jointly account for multiple evolutionary processes. This will be crucial to perform accurate
evolutionary inference in compact genomes. My long-term vision is to apply our methodological advances to
human pathogens to learn about their pop...

## Key facts

- **NIH application ID:** 10936799
- **Project number:** 1R35GM154969-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Parul Johri
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $388,750
- **Award type:** 1
- **Project period:** 2024-08-16 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10936799

## Citation

> US National Institutes of Health, RePORTER application 10936799, Jointly modeling the effects of evolutionary processes on genomic variation (1R35GM154969-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10936799. Licensed CC0.

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