Abundance, distribution, and mutation rates of homopolymeric nucleotide runs in the genome of Caenorhabditis elegans

Dee R. Denver, Krystalynne Morris, Avinash Kewalramani, Katherine E. Harris, Amy Chow, Suzanne Estes, Michael Lynch, W. Kelley Thomas

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Homopolymeric nucleotide runs, also called mononucleotide microsatellites, are a ubiquitous, dominant, and mutagenic feature of eukaryotic genomes. A clear understanding of the forces that shape patterns of homopolymer evolution, however, is lacking. We provide a focused investigation of the abundance, chromosomal distribution, and mutation spectra of the four strand-specific homopolymer types (A, T, G, C) ≥8 bp in the genome of Caenorhabditis elegans. A and T homopolymers vastly outnumber G and C HPs, and the run-length distributions of A and T homopolymers differ significantly from G and C homopolymers. A scanning window analysis of homopolymer chromosomal distribution reveals distinct clusters of homopolymer density in autosome arms that are regions of high recombination in C. elegans. Dramatic biases are detected among closely spaced homopolymers; for instance, we observe 994 A homopolymers immediately followed by a T homopolymer (5′ to 3′) and only 8 instances of T homopolymers directly followed by an A homopolymer. Empirical homopolymer mutation assays in a set of C. elegans mutation-accumulation lines reveal an ∼20-fold higher mutation rate for G and C homopolymers compared to A and T homopolymers. Nuclear A and T homopolymers are also found to mutate ∼100-fold more slowly than mitochondrial A and T homopolymers. This integrative approach yields a total nuclear genome-wide homopolymer mutation rate estimate of ∼1.6 mutations per genome per generation.

Original languageEnglish (US)
Pages (from-to)584-595
Number of pages12
JournalJournal of Molecular Evolution
Volume58
Issue number5
DOIs
StatePublished - May 1 2004
Externally publishedYes

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Keywords

  • Caenorhabditis elegans
  • Genome
  • Homopolymer
  • Microsatellite
  • Mutation

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics

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