# Causes and Population-genetic Consequences of Molecular Variation

> **NIH NIH R35** · ARIZONA STATE UNIVERSITY-TEMPE CAMPUS · 2021 · $264,420

## Abstract

Focused on elucidating the mechanisms of evolution at the molecular and population-genetic
levels, this project involves an integration of theory development and experimental work
performed in a phylogenetic comparative manner. The molecular/cellular level focus is on the
rate of error production via DNA replication, mRNA transcription, and protein translation in ~50
bacterial and eukaryotic species. This work seeks to test the drift-barrier hypothesis, which
postulates that the level of refinement that natural selection can achieve with any trait is limited
by the power of random drift and inversely proportional to the effective population size.
Measures of replication-fidelity derive from mutation accumulation in long-term sets of serially
bottlenecked replicate lines followed by whole-genome sequencing. Newly developed methods
will yield parallel estimates of the much higher rates at which inappropriate ribonucleotides
appear in mRNAs and erroneous amino acids are incorporated into proteins, allowing evaluation
of whether negative associations exist between error propagation at these two levels.
 The population-genetic mechanisms of evolution will be clarified via a project to
sequence 5000 genomes from geographically widespread isolates of the model
microcrustacean Daphnia pulex, as well as from smaller numbers of key outgroup species.
Combined with information on the fine-scaled pattern of recombination, this study will reveal the
relative magnitudes of drift, mutation, and recombination in a collection of ~60 populations, a
survey far beyond that for any other species. This will enable a test of the hypothesis that
variation at the level of gene structure and genomic architecture is directly driven by the local
population-genetic environment. The D. pulex system also has unique features for gaining
insights into two major unsolved mysteries in evolutionary genetics: the origin and long-term
effects of introns in protein-coding genes, and the causes and consequences of the loss of
meiotic recombination.
 Relevance to human health. Because mutation is the source of all variation upon which
natural selection acts, provides the fuel for the emergence of pathogens, and is the ultimate
cause of genetic disorders and cancer, our work on replication fidelity has broad significance for
diverse human-health issues. Because transcription and translation errors lead to cellular
toxicity and protein aggregation, work at these levels also has significant applied implications.
Finally, for the first time, the 5000 Genomes Project will reveal how population evolutionary
features are defined by the relative power of drift, mutation and recombination, yielding insight
into the factors driving the efficiencies and mechanisms by which all species respond to natural
selection. Elucidation of the molecular/cellular mechanisms by which meiotic production of
haploid eggs requiring fertilization is converted to ameiotic production of diploid eggs is highly
desirabl...

## Key facts

- **NIH application ID:** 10167724
- **Project number:** 5R35GM122566-06
- **Recipient organization:** ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
- **Principal Investigator:** Michael R LYNCH
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $264,420
- **Award type:** 5
- **Project period:** 2017-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167724

## Citation

> US National Institutes of Health, RePORTER application 10167724, Causes and Population-genetic Consequences of Molecular Variation (5R35GM122566-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10167724. Licensed CC0.

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