Abstract
The net rate of mutation to deleterious but nonlethal alleles and the sizes of effects of these mutations are of great significance for many evolutionary questions. Here we describe three replicate experiments in which mutations have been accumulated on chromosome 3 of Drosophila melanogaster by means of single-male backcrosses of heterozygotes for a wild-type third chromosome. Egg-to-adult viability was assayed for nonlethal homozygous chromosomes. The rates of decline in mean and increase in variance (DM and DV, respectively) were estimated. Scaled up to the diploid whole genome, the mean DM for homozygous detrimental mutations over the three experiments was between 0.8 and 1.8%. The corresponding DV estimate was approximately 0.11%. Overall, the results suggest a lower bound estimate of at least 12% for the diploid per genome mutation rate for detrimentals. The upper bound estimates for the mean selection coefficient were between 2 and 10%, depending on the method used. Mutations with selection coefficients of at least a few percent must be the major contributors to the effects detected here and are likely to be caused mostly by transposable element insertions or indels.
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- Adams M. D., Celniker S. E., Holt R. A., Evans C. A., Gocayne J. D., Amanatides P. G., Scherer S. E., Li P. W., Hoskins R. A., Galle R. F. The genome sequence of Drosophila melanogaster. Science. 2000 Mar 24;287(5461):2185–2195. doi: 10.1126/science.287.5461.2185. [DOI] [PubMed] [Google Scholar]
- Caballero A., Cusi E., García C., García-Dorado A. Accumulation of deleterious mutations: additional Drosophila melanogaster estimates and a simulation of the effects of selection. Evolution. 2002 Jun;56(6):1150–1159. doi: 10.1111/j.0014-3820.2002.tb01428.x. [DOI] [PubMed] [Google Scholar]
- Charlesworth B., Charlesworth D. Some evolutionary consequences of deleterious mutations. Genetica. 1998;102-103(1-6):3–19. [PubMed] [Google Scholar]
- Charlesworth B., Jarne P., Assimacopoulos S. The distribution of transposable elements within and between chromosomes in a population of Drosophila melanogaster. III. Element abundances in heterochromatin. Genet Res. 1994 Dec;64(3):183–197. doi: 10.1017/s0016672300032845. [DOI] [PubMed] [Google Scholar]
- Chavarrías D., López-Fanjul C., García-Dorado A. The rate of mutation and the homozygous and heterozygous mutational effects for competitive viability: a long-term experiment with Drosophila melanogaster. Genetics. 2001 Jun;158(2):681–693. doi: 10.1093/genetics/158.2.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Eggleston W. B., Johnson-Schlitz D. M., Engels W. R. P-M hybrid dysgenesis does not mobilize other transposable element families in D. melanogaster. Nature. 1988 Jan 28;331(6154):368–370. doi: 10.1038/331368a0. [DOI] [PubMed] [Google Scholar]
- Fry J. D. Rapid mutational declines of viability in Drosophila. Genet Res. 2001 Feb;77(1):53–60. doi: 10.1017/s0016672300004882. [DOI] [PubMed] [Google Scholar]
- Fry James D., Heinsohn Stefanie L. Environment dependence of mutational parameters for viability in Drosophila melanogaster. Genetics. 2002 Jul;161(3):1155–1167. doi: 10.1093/genetics/161.3.1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fry James D., Nuzhdin Sergey V. Dominance of mutations affecting viability in Drosophila melanogaster. Genetics. 2003 Apr;163(4):1357–1364. doi: 10.1093/genetics/163.4.1357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- García-Dorado A., Caballero A. On the average coefficient of dominance of deleterious spontaneous mutations. Genetics. 2000 Aug;155(4):1991–2001. doi: 10.1093/genetics/155.4.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- García-Dorado Aurora, Gallego Araceli. Comparing analysis methods for mutation-accumulation data: a simulation study. Genetics. 2003 Jun;164(2):807–819. doi: 10.1093/genetics/164.2.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Halligan Daniel L., Eyre-Walker Adam, Andolfatto Peter, Keightley Peter D. Patterns of evolutionary constraints in intronic and intergenic DNA of Drosophila. Genome Res. 2004 Feb;14(2):273–279. doi: 10.1101/gr.1329204. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Houle D., Hoffmaster D. K., Assimacopoulos S., Charlesworth B. The genomic mutation rate for fitness in Drosophila. Nature. 1992 Sep 3;359(6390):58–60. doi: 10.1038/359058a0. [DOI] [PubMed] [Google Scholar]
- Houle D., Kondrashov A. S., Yampolsky L. Y., Caldwell S., Steponkus P. L. The effect of cryopreservation on the lethal mutation rate in Drosophila melanogaster. Genet Res. 1997 Jun;69(3):209–213. doi: 10.1017/s0016672397002760. [DOI] [PubMed] [Google Scholar]
- Jensen Mark A., Charlesworth Brian, Kreitman Martin. Patterns of genetic variation at a chromosome 4 locus of Drosophila melanogaster and D. simulans. Genetics. 2002 Feb;160(2):493–507. doi: 10.1093/genetics/160.2.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keightley P. D., Eyre-Walker A. Deleterious mutations and the evolution of sex. Science. 2000 Oct 13;290(5490):331–333. doi: 10.1126/science.290.5490.331. [DOI] [PubMed] [Google Scholar]
- 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]
- Keightley Peter D., Lynch Michael. Toward a realistic model of mutations affecting fitness. Evolution. 2003 Mar;57(3):683–689. doi: 10.1111/j.0014-3820.2003.tb01561.x. [DOI] [PubMed] [Google Scholar]
- Kondrashov A. S. Classification of hypotheses on the advantage of amphimixis. J Hered. 1993 Sep-Oct;84(5):372–387. doi: 10.1093/oxfordjournals.jhered.a111358. [DOI] [PubMed] [Google Scholar]
- Kondrashov A. S. Deleterious mutations and the evolution of sexual reproduction. Nature. 1988 Dec 1;336(6198):435–440. doi: 10.1038/336435a0. [DOI] [PubMed] [Google Scholar]
- Lyman R. F., Lawrence F., Nuzhdin S. V., Mackay T. F. Effects of single P-element insertions on bristle number and viability in Drosophila melanogaster. Genetics. 1996 May;143(1):277–292. doi: 10.1093/genetics/143.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mackay T. F., Lyman R. F., Jackson M. S. Effects of P element insertions on quantitative traits in Drosophila melanogaster. Genetics. 1992 Feb;130(2):315–332. doi: 10.1093/genetics/130.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maside X., Assimacopoulos S., Charlesworth B. Rates of movement of transposable elements on the second chromosome of Drosophila melanogaster. Genet Res. 2000 Jun;75(3):275–284. doi: 10.1017/s0016672399004474. [DOI] [PubMed] [Google Scholar]
- 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]
- Nuzhdin S. V., Pasyukova E. G., Morozova E. A., Flavell A. J. Quantitative genetic analysis of copia retrotransposon activity in inbred Drosophila melanogaster lines. Genetics. 1998 Oct;150(2):755–766. doi: 10.1093/genetics/150.2.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rivero Ana, Balloux Francois, West Stuart A. Testing for epistasis between deleterious mutations in a parasitoid wasp. Evolution. 2003 Jul;57(7):1698–1703. doi: 10.1111/j.0014-3820.2003.tb00375.x. [DOI] [PubMed] [Google Scholar]
- Shabalina S. A., Yampolsky LYu, Kondrashov A. S. Rapid decline of fitness in panmictic populations of Drosophila melanogaster maintained under relaxed natural selection. Proc Natl Acad Sci U S A. 1997 Nov 25;94(24):13034–13039. doi: 10.1073/pnas.94.24.13034. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shaw Frank H., Geyer Charles J., Shaw Ruth G. A comprehensive model of mutations affecting fitness and inferences for Arabidopsis thaliana. Evolution. 2002 Mar;56(3):453–463. doi: 10.1111/j.0014-3820.2002.tb01358.x. [DOI] [PubMed] [Google Scholar]
- Simmons M. J., Johnson N. A., Fahey T. M., Nellett S. M., Raymond J. D. High mutability in male hybrids of Drosophila melanogaster. Genetics. 1980 Oct;96(2):479–480. doi: 10.1093/genetics/96.2.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Szafraniec Krzysztof, Wloch Dominika M., Sliwa Piotr, Borts Rhona H., Korona Ryszard. Small fitness effects and weak genetic interactions between deleterious mutations in heterozygous loci of the yeast Saccharomyces cerevisiae. Genet Res. 2003 Aug;82(1):19–31. doi: 10.1017/s001667230300630x. [DOI] [PubMed] [Google Scholar]