# Characterizing the genetic and evolutionary determinants of population variation in transcriptional responses to pathogens

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2024 · $517,611

## Abstract

Project Summary
Pathogens are one of the strongest selective pressures on the human genome. As modern humans migrated
out of Africa, they encountered markedly different pathogenic environments, likely resulting in population-specific
selection of immune phenotypes. Consistent with this hypothesis, some of the most compelling evidence for
local positive selection in the human genome has been detected among genes involved in immunity and host
defense. Yet, our understanding of the role that local adaptation plays in shaping phenotypic variation in immune
responses across populations is still in its infancy. To better understand the complex relationship between
pathogens and host adaptation we propose to explore the effects of natural selection and genetic ancestry on
gene expression, epigenetic traits, and immune responses to infection across a large array of human
populations. Our research program is grounded on three outstanding questions in the fields of genomics,
population variation in host response to pathogens, and evolutionary biology: (i) the degree to which immune
responses to pathogens are differentiated across ancestry groups; (ii) the genetic variants that account for such
differences; and (iii) the evolutionary mechanisms (neutral genetic drift vs positive selection) that led to the
establishment of these variants in modern human populations. Addressing these questions is not only important
for understanding the recent evolution of the human immune system but may also help reveal the molecular
basis to interindividual differences in susceptibility to infectious diseases, chronic inflammatory disorders, and
autoimmune disorders.

## Key facts

- **NIH application ID:** 10765526
- **Project number:** 1R35GM152227-01
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Luis Bruno Barreiro
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $517,611
- **Award type:** 1
- **Project period:** 2024-07-10 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10765526

## Citation

> US National Institutes of Health, RePORTER application 10765526, Characterizing the genetic and evolutionary determinants of population variation in transcriptional responses to pathogens (1R35GM152227-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10765526. Licensed CC0.

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