# Leveraging phylogenetic approaches to investigate the evolution of gene expression

> **NIH NIH R35** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $40,734

## Abstract

SUMMARY
Across the biomedical sciences there has been an increased recognition that many key questions
in these fields require phylogenetic thinking and approaches. My group has a very strong track
record of making fundamental methodological contributions that have changed how biologists
think about and analyze phylogenetically structured data and of finding new applications for
these methods. My group’s current research is focused on two main themes, both related to the
evolution of genomic function.
 First, we will use phylogenetic comparative approaches to investigate the dynamics of
gene expression evolution across species. We will first assess the appropriateness of adopting
phylogenetic models of phenotypic evolution for describing changes in gene expression using an
approach we have previously developed. This will enable us to assess the robustness of findings
regarding the relative importance of different evolutionary processes in generating interspecific
diversity and help us develop the next-generation of models, specifically tailored to functional
genomic data. We will then build a mechanistic model that will allow us and other researchers to
test for associations between gene expression evolution and sequence evolution in the promoter
regions.
 Second, we will study the evolution of Immunoglobulin genes, which encode the unique
antigen recognition sequences of B cells, which produce antibodies. We will investigate this at
two nested levels: the evolution of the B cell repertoire over time and in response to pathogens
and the evolution of the germline Immunoglobulin genes. To examine changes in the B cell
repertoire, we will adopt approaches that our research group has pioneered in the context of
macroevolution, to characterize the dynamics of the system. We are specifically interested in
estimating the rate of somatic mutation and the number of distinct clonal lineages that are
expanding in response to an infectious disease. There is accumulating evidence that variation in
the evolved response of B cells is associated with inter-individual variation in the germline
Immunoglobulin genes. However, the underpinning mechanism remains unclear as do the
reasons there appears to be so much diversity at these loci across individuals. We will derive an
evolutionary model, and parameterize it using comparative genomic data, to evaluate the
plausibility of alternative hypotheses for explaining both of these observations.

## Key facts

- **NIH application ID:** 10894741
- **Project number:** 5R35GM151348-02
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Matthew Wesley Pennell
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $40,734
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-01-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894741

## Citation

> US National Institutes of Health, RePORTER application 10894741, Leveraging phylogenetic approaches to investigate the evolution of gene expression (5R35GM151348-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10894741. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*