High mutation rate and predominance of insertions in the Caenohabditis elegans nuclear genome

Dee R. Denver, Krystalynne Morris, Michael Lynch, W. Kelley Thomas

Research output: Contribution to journalArticle

242 Citations (Scopus)

Abstract

Mutations have pivotal functions in the onset of genetic diseases and are the fundamental substrate for evolution. However, present estimates of the spontaneous mutation rate and spectrum are derived from indirect and biased measurements. For instance, mutation rate estimates for Caenorhabditis elegans are extrapolated from observations on a few genetic loci with visible phenotypes and vary over an order of magnitude. Alternative approaches in mammals, relying on phylogenetic comparisons of pseudogene loci and fourfold degenerate codon positions, suffer from uncertainties in the actual number of generations separating the compared species and the inability to exclude biases associated with natural selection. Here we provide a direct and unbiased estimate of the nuclear mutation rate and its molecular spectrum with a set of C. elegans mutation-accumulation lines that reveal a mutation rate about tenfold higher than previous indirect estimates and an excess of insertions over deletions. Because deletions dominate patterns of C. elegans pseudogene variation, our observations indicate that natural selection might be significant in promoting small genome size, and challenge the prevalent assumption that pseudogene divergence accurately reflects the spontaneous mutation spectrum.

Original languageEnglish (US)
Pages (from-to)679-682
Number of pages4
JournalNature
Volume430
Issue number7000
DOIs
StatePublished - Aug 5 2004
Externally publishedYes

Fingerprint

Mutation Rate
Pseudogenes
Caenorhabditis elegans
Genome
Genetic Selection
Genome Size
Mutation
Inborn Genetic Diseases
Genetic Loci
Codon
Uncertainty
Mammals
Phenotype

ASJC Scopus subject areas

  • General

Cite this

High mutation rate and predominance of insertions in the Caenohabditis elegans nuclear genome. / Denver, Dee R.; Morris, Krystalynne; Lynch, Michael; Thomas, W. Kelley.

In: Nature, Vol. 430, No. 7000, 05.08.2004, p. 679-682.

Research output: Contribution to journalArticle

Denver, Dee R. ; Morris, Krystalynne ; Lynch, Michael ; Thomas, W. Kelley. / High mutation rate and predominance of insertions in the Caenohabditis elegans nuclear genome. In: Nature. 2004 ; Vol. 430, No. 7000. pp. 679-682.
@article{a85348b0564d4fb9b6bd9a7e10ed7557,
title = "High mutation rate and predominance of insertions in the Caenohabditis elegans nuclear genome",
abstract = "Mutations have pivotal functions in the onset of genetic diseases and are the fundamental substrate for evolution. However, present estimates of the spontaneous mutation rate and spectrum are derived from indirect and biased measurements. For instance, mutation rate estimates for Caenorhabditis elegans are extrapolated from observations on a few genetic loci with visible phenotypes and vary over an order of magnitude. Alternative approaches in mammals, relying on phylogenetic comparisons of pseudogene loci and fourfold degenerate codon positions, suffer from uncertainties in the actual number of generations separating the compared species and the inability to exclude biases associated with natural selection. Here we provide a direct and unbiased estimate of the nuclear mutation rate and its molecular spectrum with a set of C. elegans mutation-accumulation lines that reveal a mutation rate about tenfold higher than previous indirect estimates and an excess of insertions over deletions. Because deletions dominate patterns of C. elegans pseudogene variation, our observations indicate that natural selection might be significant in promoting small genome size, and challenge the prevalent assumption that pseudogene divergence accurately reflects the spontaneous mutation spectrum.",
author = "Denver, {Dee R.} and Krystalynne Morris and Michael Lynch and Thomas, {W. Kelley}",
year = "2004",
month = "8",
day = "5",
doi = "10.1038/nature02697",
language = "English (US)",
volume = "430",
pages = "679--682",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7000",

}

TY - JOUR

T1 - High mutation rate and predominance of insertions in the Caenohabditis elegans nuclear genome

AU - Denver, Dee R.

AU - Morris, Krystalynne

AU - Lynch, Michael

AU - Thomas, W. Kelley

PY - 2004/8/5

Y1 - 2004/8/5

N2 - Mutations have pivotal functions in the onset of genetic diseases and are the fundamental substrate for evolution. However, present estimates of the spontaneous mutation rate and spectrum are derived from indirect and biased measurements. For instance, mutation rate estimates for Caenorhabditis elegans are extrapolated from observations on a few genetic loci with visible phenotypes and vary over an order of magnitude. Alternative approaches in mammals, relying on phylogenetic comparisons of pseudogene loci and fourfold degenerate codon positions, suffer from uncertainties in the actual number of generations separating the compared species and the inability to exclude biases associated with natural selection. Here we provide a direct and unbiased estimate of the nuclear mutation rate and its molecular spectrum with a set of C. elegans mutation-accumulation lines that reveal a mutation rate about tenfold higher than previous indirect estimates and an excess of insertions over deletions. Because deletions dominate patterns of C. elegans pseudogene variation, our observations indicate that natural selection might be significant in promoting small genome size, and challenge the prevalent assumption that pseudogene divergence accurately reflects the spontaneous mutation spectrum.

AB - Mutations have pivotal functions in the onset of genetic diseases and are the fundamental substrate for evolution. However, present estimates of the spontaneous mutation rate and spectrum are derived from indirect and biased measurements. For instance, mutation rate estimates for Caenorhabditis elegans are extrapolated from observations on a few genetic loci with visible phenotypes and vary over an order of magnitude. Alternative approaches in mammals, relying on phylogenetic comparisons of pseudogene loci and fourfold degenerate codon positions, suffer from uncertainties in the actual number of generations separating the compared species and the inability to exclude biases associated with natural selection. Here we provide a direct and unbiased estimate of the nuclear mutation rate and its molecular spectrum with a set of C. elegans mutation-accumulation lines that reveal a mutation rate about tenfold higher than previous indirect estimates and an excess of insertions over deletions. Because deletions dominate patterns of C. elegans pseudogene variation, our observations indicate that natural selection might be significant in promoting small genome size, and challenge the prevalent assumption that pseudogene divergence accurately reflects the spontaneous mutation spectrum.

UR - http://www.scopus.com/inward/record.url?scp=3943059570&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=3943059570&partnerID=8YFLogxK

U2 - 10.1038/nature02697

DO - 10.1038/nature02697

M3 - Article

C2 - 15295601

AN - SCOPUS:3943059570

VL - 430

SP - 679

EP - 682

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7000

ER -