# 100K spontaneous mutations: the foundation for an evolutionary systems biology of C. elegans

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $321,507

## Abstract

Project Summary
Technological advances have enabled biologists to categorize entire "omes"– genomes, but also
transcriptomes, proteomes, metabolomes, etc., down to the level of individual cells. Systems Biology is an
ascendant branch of biology, with the goal of understanding the interactions between the molecular
components of an organism, and how those interactions function to build, operate, and maintain the organism
in the context of its environment. The number of such interactions is vast, but experience suggests that there
will be underlying consistent rules. A potential way forward is to scrutinize features of a large system – a
transcriptome, for example – for consistent signatures of natural selection. A powerful way to reveal the
signature of natural selection is to compare the genetic variation introduced by mutation to the standing genetic
variation in the population. That is because the standing genetic variation has been scrutinized by natural
selection. A consistent discrepancy between the genetic variation introduced by spontaneous mutation and
the standing genetic variation present in a species is an unmistakable signature of natural selection. In turn,
identifying some feature of an organism that is demonstrably under natural selection is prima facie evidence
that the feature has a significant biological function, even if the function is not immediately obvious.
 The raw material for systems biologists is a (large) set of measures of the abundance of individual
transcripts, proteins, metabolites, etc. It seems likely that in most cases the mutational target of an individual
transcript, etc., will be small. If the mutational target is small, many genomes must be screened to provide a
reliable characterization of the mutational process responsible for producing genetic variation in the trait of
interest. The goal of the proposed work is to construct a large set of replicate populations of the model
nematode Caenorhabditis elegans that have evolved under minimal natural selection, thereby allowing all but
the most highly deleterious mutations to accumulate as if they are invisible to natural selection. Ultimately, the
set of mutation accumulation lines are expected to harbor approximately 100,000 spontaneous mutations. C.
elegans provides major advantages over other animal models in this context, the most important being that
nematodes can be easily and reliably cryopreserved. The resource will therefore be durable, and experiments
can be done on the (nearly) exact same genetic stock for decades hence. The genomes of the lines will be
sequenced, thereby allowing researchers to associate genotypes with their specific traits of interest. Both the
lines themselves and the genome sequences will be made immediately available as a community resource.
 Systems Biology is inherently concerned with interactions between genes, and between genes and the
environment. Model organisms such as C. elegans are especially valuable in that regard bec...

## Key facts

- **NIH application ID:** 9915935
- **Project number:** 5R01GM127433-03
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** CHARLES F BAER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $321,507
- **Award type:** 5
- **Project period:** 2018-08-06 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9915935

## Citation

> US National Institutes of Health, RePORTER application 9915935, 100K spontaneous mutations: the foundation for an evolutionary systems biology of C. elegans (5R01GM127433-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9915935. Licensed CC0.

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