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. 2000 Mar;154(3):1193–1201. doi: 10.1093/genetics/154.3.1193

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

P D Keightley 1, T M Bataillon 1
PMCID: PMC1461002  PMID: 10757763

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.

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Selected References

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  1. Ashburner M., Misra S., Roote J., Lewis S. E., Blazej R., Davis T., Doyle C., Galle R., George R., Harris N. 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. doi: 10.1093/genetics/153.1.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Davies E. K., Peters A. D., Keightley P. D. High frequency of cryptic deleterious mutations in Caenorhabditis elegans. Science. 1999 Sep 10;285(5434):1748–1751. doi: 10.1126/science.285.5434.1748. [DOI] [PubMed] [Google Scholar]
  3. Deng H. W., Fu Y. X. On the three methods for estimating deleterious genomic mutation parameters. Genet Res. 1998 Jun;71(3):223–236. doi: 10.1017/s0016672398003255. [DOI] [PubMed] [Google Scholar]
  4. Deng H. W., Li J., Li J. L. On the experimental design and data analysis of mutation accumulation experiments. Genet Res. 1999 Apr;73(2):147–164. doi: 10.1017/s0016672398003681. [DOI] [PubMed] [Google Scholar]
  5. 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. doi: 10.1093/genetics/109.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fry J. D., Keightley P. D., Heinsohn S. L., Nuzhdin S. V. 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. doi: 10.1073/pnas.96.2.574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Johnson T. E., Hutchinson E. W. Absence of strong heterosis for life span and other life history traits in Caenorhabditis elegans. Genetics. 1993 Jun;134(2):465–474. doi: 10.1093/genetics/134.2.465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Keightley P. D., 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. doi: 10.1073/pnas.94.8.3823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Keightley P. D., Eyre-Walker A. Terumi Mukai and the riddle of deleterious mutation rates. Genetics. 1999 Oct;153(2):515–523. doi: 10.1093/genetics/153.2.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Keightley P. D. Inference of genome-wide mutation rates and distributions of mutation effects for fitness traits: a simulation study. Genetics. 1998 Nov;150(3):1283–1293. doi: 10.1093/genetics/150.3.1283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Keightley P. D. Nature of deleterious mutation load in Drosophila. Genetics. 1996 Dec;144(4):1993–1999. doi: 10.1093/genetics/144.4.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Keightley P. D. The distribution of mutation effects on viability in Drosophila melanogaster. Genetics. 1994 Dec;138(4):1315–1322. doi: 10.1093/genetics/138.4.1315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kibota T. T., Lynch M. Estimate of the genomic mutation rate deleterious to overall fitness in E. coli. Nature. 1996 Jun 20;381(6584):694–696. doi: 10.1038/381694a0. [DOI] [PubMed] [Google Scholar]
  14. 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. doi: 10.1093/genetics/50.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mukai T., Chigusa S. I., Mettler L. E., Crow J. F. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics. 1972 Oct;72(2):335–355. doi: 10.1093/genetics/72.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Simmen M. W., Leitgeb S., Clark V. H., Jones S. J., Bird A. Gene number in an invertebrate chordate, Ciona intestinalis. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4437–4440. doi: 10.1073/pnas.95.8.4437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Simmons M. J., Crow J. F. Mutations affecting fitness in Drosophila populations. Annu Rev Genet. 1977;11:49–78. doi: 10.1146/annurev.ge.11.120177.000405. [DOI] [PubMed] [Google Scholar]
  18. Vassilieva L. L., Lynch M. The rate of spontaneous mutation for life-history traits in Caenorhabditis elegans. Genetics. 1999 Jan;151(1):119–129. doi: 10.1093/genetics/151.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]

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