• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Mar 2000; 154(3): 1193–1201.
PMCID: PMC1461002

Multigeneration maximum-likelihood analysis applied to mutation-accumulation experiments in Caenorhabditis elegans.

Abstract

We develop a maximum-likelihood (ML) approach to estimate genomic mutation rates (U) and average homozygous mutation effects (s) from mutation-accumulation (MA) experiments in which phenotypic assays are carried out in several generations. We use simulations to compare the procedure's performance with the method of moments traditionally used to analyze MA data. Similar precision is obtained if mutation effects are small relative to the environmental standard deviation, but ML can give estimates of mutation parameters that have lower sampling variances than those obtained by the method of moments if mutations with large effects have accumulated. The inclusion of data from intermediate generations may improve the precision. We analyze life-history trait data from two Caenorhabditis elegans MA experiments. Under a model with equal mutation effects, the two experiments provide similar estimates for U of approximately 0.005 per haploid, averaged over traits. Estimates of s are more divergent and average at -0.51 and -0.13 in the two studies. Detailed analysis shows that changes of mean and variance of genetic values of MA lines in both C. elegans experiments are dominated by mutations with large effects, but the analysis does not rule out the presence of a large class of deleterious mutations with very small effects.

Full Text

The Full Text of this article is available as a PDF (141K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Johnson TE, Hutchinson EW. Absence of strong heterosis for life span and other life history traits in Caenorhabditis elegans. Genetics. 1993 Jun;134(2):465–474. [PMC free article] [PubMed]
  • Keightley PD. The distribution of mutation effects on viability in Drosophila melanogaster. Genetics. 1994 Dec;138(4):1315–1322. [PMC free article] [PubMed]
  • Keightley PD. Nature of deleterious mutation load in Drosophila. Genetics. 1996 Dec;144(4):1993–1999. [PMC free article] [PubMed]
  • Keightley PD. Inference of genome-wide mutation rates and distributions of mutation effects for fitness traits: a simulation study. Genetics. 1998 Nov;150(3):1283–1293. [PMC free article] [PubMed]
  • Keightley PD, Caballero A. Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3823–3827. [PMC free article] [PubMed]
  • Keightley PD, Eyre-Walker A. Terumi Mukai and the riddle of deleterious mutation rates. Genetics. 1999 Oct;153(2):515–523. [PMC free article] [PubMed]
  • Kibota TT, Lynch M. Estimate of the genomic mutation rate deleterious to overall fitness in E. coli. Nature. 1996 Jun 20;381(6584):694–696. [PubMed]
  • Ashburner M, Misra S, Roote J, Lewis SE, Blazej R, Davis T, Doyle C, Galle R, George R, Harris N, et al. An exploration of the sequence of a 2.9-Mb region of the genome of Drosophila melanogaster: the Adh region. Genetics. 1999 Sep;153(1):179–219. [PMC free article] [PubMed]
  • MUKAI T. THE GENETIC STRUCTURE OF NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER. I. SPONTANEOUS MUTATION RATE OF POLYGENES CONTROLLING VIABILITY. Genetics. 1964 Jul;50:1–19. [PMC free article] [PubMed]
  • Mukai T, Chigusa SI, Mettler LE, Crow JF. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics. 1972 Oct;72(2):335–355. [PMC free article] [PubMed]
  • Davies EK, Peters AD, Keightley PD. High frequency of cryptic deleterious mutations in Caenorhabditis elegans. Science. 1999 Sep 10;285(5434):1748–1751. [PubMed]
  • Deng HW, Fu YX. On the three methods for estimating deleterious genomic mutation parameters. Genet Res. 1998 Jun;71(3):223–236. [PubMed]
  • Deng HW, Li J, Li JL. On the experimental design and data analysis of mutation accumulation experiments. Genet Res. 1999 Apr;73(2):147–164. [PubMed]
  • Simmen MW, Leitgeb S, Clark VH, Jones SJ, Bird A. Gene number in an invertebrate chordate, Ciona intestinalis. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4437–4440. [PMC free article] [PubMed]
  • Eide D, Anderson P. The gene structures of spontaneous mutations affecting a Caenorhabditis elegans myosin heavy chain gene. Genetics. 1985 Jan;109(1):67–79. [PMC free article] [PubMed]
  • Simmons MJ, Crow JF. Mutations affecting fitness in Drosophila populations. Annu Rev Genet. 1977;11:49–78. [PubMed]
  • Vassilieva LL, Lynch M. The rate of spontaneous mutation for life-history traits in Caenorhabditis elegans. Genetics. 1999 Jan;151(1):119–129. [PMC free article] [PubMed]
  • Fry JD, Keightley PD, Heinsohn SL, Nuzhdin SV. New estimates of the rates and effects of mildly deleterious mutation in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1999 Jan 19;96(2):574–579. [PMC free article] [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...