# Genomic and systemic approaches to evolutionary mechanisms

> **NIH NIH R35** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $387,837

## Abstract

Project Summary
The long-term objective of the PI's research program is to discover and understand general principles of
evolution in terms of molecular genetic mechanisms and driving forces. This is a rapidly progressing area,
thanks to the technological revolution in molecular biology and genomics, rapid accumulation of genome
sequences and functional genomic data, and most importantly, conceptual developments in various fields of
biology. Genomic and systemic approaches to evolution are especially valuable, because the genomic
approach allows assessing the generalities and relative contributions of individual mechanisms discovered and
the systemic approach helps refocus the study of evolutionary processes from roles of individual
genes/mutations to those of interactions among genes/mutations (and the environment), which are key to
uncovering the inner workings and evolution of biological systems. The PI's lab studies evolutionary
mechanisms from genomic and systemic perspectives using multiple model systems (mostly yeast and
mammals) and a combination of theoretical modeling, computer simulation, integrative data analysis,
laboratory experimental evolution, and molecular and genomic experimentation. This proposal centers on two
related themes that are of fundamental importance to evolution: epistasis and pleiotropy. On the topic of
epistasis, the PI and his team will characterize patterns of intragenic and intergenic epistasis by mapping
fitness landscapes of representative genes and joint fitness landscapes of pairs of interacting genes, study the
genetic background dependency of gene essentiality at the genomic scale, experimentally test the hypothesis
that the existence and persistence of RNA editing is explained by evolutionary entrenchment, and attempt to
resolve the apparently contradictory inferences of epistasis patterns from adaptive evolution and mutation
accumulation. On the topic of pleiotropy, the PI and his team will map multi-environment fitness landscapes of
representative genes to study general patterns of environmental pleiotropy of mutations, identify common loci
of environmental adaptations, quantify the influence of pleiotropy on molecular adaptations in changing
environments, and assess the impact of pleiotropy on the rate of phenotypic evolution and human aging and
disease. Together, these projects promise to deepen the understanding of the genetic mechanisms and driving
forces of evolution and shed light on disease mechanisms and prevalence.

## Key facts

- **NIH application ID:** 10085470
- **Project number:** 1R35GM139484-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** JIANZHI ZHANG
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $387,837
- **Award type:** 1
- **Project period:** 2021-02-01 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085470

## Citation

> US National Institutes of Health, RePORTER application 10085470, Genomic and systemic approaches to evolutionary mechanisms (1R35GM139484-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10085470. Licensed CC0.

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