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. 2002 Oct;162(2):755–765. doi: 10.1093/genetics/162.2.755

Spontaneous mutational variation for body size in Caenorhabditis elegans.

Ricardo B R Azevedo 1, Peter D Keightley 1, Camilla Laurén-Määttä 1, Larissa L Vassilieva 1, Michael Lynch 1, Armand M Leroi 1
PMCID: PMC1462287  PMID: 12399386

Abstract

We measured the impact of new mutations on genetic variation for body size in two independent sets of C. elegans spontaneous mutation-accumulation (MA) lines, derived from the N2 strain, that had been maintained by selfing for 60 or 152 generations. The two sets of lines gave broadly consistent results. The change of among-line genetic variation between cryopreserved controls and the MA lines implied that broad sense heritability increased by 0.4% per generation. Overall, MA reduced mean body size by approximately 0.1% per generation. The genome-wide rate for mutations with detectable effects on size was estimated to be approximately 0.0025 per haploid genome per generation, and their mean effects were approximately 20%. The proportion of mutations that increase body size was estimated by maximum likelihood to be no more than 20%, suggesting that the amount of mutational variation available for selection for increased size could be quite small. This hypothesis was supported by an artificial selection experiment on adult body size, started from a single highly inbred N2 individual. We observed a strongly asymmetrical response to selection of a magnitude consistent with the input of mutational variance observed in the MA experiment.

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Selected References

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  1. Caballero A., Hill W. G. Effects of partial inbreeding on fixation rates and variation of mutant genes. Genetics. 1992 Jun;131(2):493–507. doi: 10.1093/genetics/131.2.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Daniels S. A., Ailion M., Thomas J. H., Sengupta P. egl-4 acts through a transforming growth factor-beta/SMAD pathway in Caenorhabditis elegans to regulate multiple neuronal circuits in response to sensory cues. Genetics. 2000 Sep;156(1):123–141. doi: 10.1093/genetics/156.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Denver D. R., Morris K., Lynch M., Vassilieva L. L., Thomas W. K. High direct estimate of the mutation rate in the mitochondrial genome of Caenorhabditis elegans. Science. 2000 Sep 29;289(5488):2342–2344. doi: 10.1126/science.289.5488.2342. [DOI] [PubMed] [Google Scholar]
  4. Flemming A. J., Shen Z. Z., Cunha A., Emmons S. W., Leroi A. M. Somatic polyploidization and cellular proliferation drive body size evolution in nematodes. Proc Natl Acad Sci U S A. 2000 May 9;97(10):5285–5290. doi: 10.1073/pnas.97.10.5285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fraser A. G., Kamath R. S., Zipperlen P., Martinez-Campos M., Sohrmann M., Ahringer J. Functional genomic analysis of C. elegans chromosome I by systematic RNA interference. Nature. 2000 Nov 16;408(6810):325–330. doi: 10.1038/35042517. [DOI] [PubMed] [Google Scholar]
  6. Fry J. D., deRonde K. A., Mackay T. F. Polygenic mutation in Drosophila melanogaster: genetic analysis of selection lines. Genetics. 1995 Mar;139(3):1293–1307. doi: 10.1093/genetics/139.3.1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gems D., Riddle D. L. Defining wild-type life span in Caenorhabditis elegans. J Gerontol A Biol Sci Med Sci. 2000 May;55(5):B215–B219. doi: 10.1093/gerona/55.5.b215. [DOI] [PubMed] [Google Scholar]
  8. Hill W. G. Rates of change in quantitative traits from fixation of new mutations. Proc Natl Acad Sci U S A. 1982 Jan;79(1):142–145. doi: 10.1073/pnas.79.1.142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Houle D., Morikawa B., Lynch M. Comparing mutational variabilities. Genetics. 1996 Jul;143(3):1467–1483. doi: 10.1093/genetics/143.3.1467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Keightley P. D., Bataillon T. M. Multigeneration maximum-likelihood analysis applied to mutation-accumulation experiments in Caenorhabditis elegans. Genetics. 2000 Mar;154(3):1193–1201. doi: 10.1093/genetics/154.3.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Keightley P. D., Davies E. K., Peters A. D., Shaw R. G. Properties of ethylmethane sulfonate-induced mutations affecting life-history traits in Caenorhabditis elegans and inferences about bivariate distributions of mutation effects. Genetics. 2000 Sep;156(1):143–154. doi: 10.1093/genetics/156.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Keightley P. D. Genetic basis of response to 50 generations of selection on body weight in inbred mice. Genetics. 1998 Apr;148(4):1931–1939. doi: 10.1093/genetics/148.4.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Keightley P. D., Ohnishi O. EMS-induced polygenic mutation rates for nine quantitative characters in Drosophila melanogaster. Genetics. 1998 Feb;148(2):753–766. doi: 10.1093/genetics/148.2.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Knight C. G., Azevedo R. B., Leroi A. M. Testing life-history pleiotropy in Caenorhabditis elegans. Evolution. 2001 Sep;55(9):1795–1804. doi: 10.1111/j.0014-3820.2001.tb00828.x. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. López M. A., López-Fanjul C. Spontaneous mutation for a quantitative trait in Drosophila melanogaster. II. Distribution of mutant effects on the trait and fitness. Genet Res. 1993 Apr;61(2):117–126. doi: 10.1017/s0016672300031220. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Mackay T. F., Fry J. D., Lyman R. F., Nuzhdin S. V. Polygenic mutation in Drosophila melanogaster: estimates from response to selection of inbred strains. Genetics. 1994 Mar;136(3):937–951. doi: 10.1093/genetics/136.3.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mackay T. F., Fry J. D. Polygenic mutation in Drosophila melanogaster: genetic interactions between selection lines and candidate quantitative trait loci. Genetics. 1996 Oct;144(2):671–688. doi: 10.1093/genetics/144.2.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Maeda I., Kohara Y., Yamamoto M., Sugimoto A. Large-scale analysis of gene function in Caenorhabditis elegans by high-throughput RNAi. Curr Biol. 2001 Feb 6;11(3):171–176. doi: 10.1016/s0960-9822(01)00052-5. [DOI] [PubMed] [Google Scholar]
  24. McCabe J., French V., Partridge L. Joint regulation of cell size and cell number in the wing blade of Drosophila melanogaster. Genet Res. 1997 Feb;69(1):61–68. doi: 10.1017/s0016672397002620. [DOI] [PubMed] [Google Scholar]
  25. Morita K., Chow K. L., Ueno N. Regulation of body length and male tail ray pattern formation of Caenorhabditis elegans by a member of TGF-beta family. Development. 1999 Mar;126(6):1337–1347. doi: 10.1242/dev.126.6.1337. [DOI] [PubMed] [Google Scholar]
  26. Nyström Josefin, Shen Zai-Zhong, Aili Margareta, Flemming Anthony J., Leroi Armand, Tuck Simon. Increased or decreased levels of Caenorhabditis elegans lon-3, a gene encoding a collagen, cause reciprocal changes in body length. Genetics. 2002 May;161(1):83–97. doi: 10.1093/genetics/161.1.83. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Partridge L., Langelan R., Fowler K., Zwaan B., French V. Correlated responses to selection on body size in Drosophila melanogaster. Genet Res. 1999 Aug;74(1):43–54. doi: 10.1017/s0016672399003778. [DOI] [PubMed] [Google Scholar]
  28. Santiago E., Albornoz J., Domínguez A., Toro M. A., López-Fanjul C. The distribution of spontaneous mutations on quantitative traits and fitness in Drosophila melanogaster. Genetics. 1992 Nov;132(3):771–781. doi: 10.1093/genetics/132.3.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Shabalina S. A., Kondrashov A. S. Pattern of selective constraint in C. elegans and C. briggsae genomes. Genet Res. 1999 Aug;74(1):23–30. doi: 10.1017/s0016672399003821. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Suzuki Y., Yandell M. D., Roy P. J., Krishna S., Savage-Dunn C., Ross R. M., Padgett R. W., Wood W. B. A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans. Development. 1999 Jan;126(2):241–250. doi: 10.1242/dev.126.2.241. [DOI] [PubMed] [Google Scholar]
  32. TANTAWY A. O., MALLAH G. S., TEWFIK H. R. STUDIES ON NATURAL POPULATIONS OF DROSOPHILA. II. HERITABILITY AND RESPONSE TO SELECTION FOR WING LENGTH IN DROSOPHILA MELANOGASTER AND D. SIMULANS AT DIFFERENT TEMPERATURES. Genetics. 1964 Jun;49:935–948. doi: 10.1093/genetics/49.6.935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Vassilieva L. L., Hook A. M., Lynch M. The fitness effects of spontaneous mutations in Caenorhabditis elegans. Evolution. 2000 Aug;54(4):1234–1246. doi: 10.1111/j.0014-3820.2000.tb00557.x. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Wayne M. L., Mackay T. F. Quantitative genetics of ovariole number in Drosophila melanogaster. II. Mutational variation and genotype-environment interaction. Genetics. 1998 Jan;148(1):201–210. doi: 10.1093/genetics/148.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yang H. P., Tanikawa A. Y., Van Voorhies W. A., Silva J. C., Kondrashov A. S. Whole-genome effects of ethyl methanesulfonate-induced mutation on nine quantitative traits in outbred Drosophila melanogaster. Genetics. 2001 Mar;157(3):1257–1265. doi: 10.1093/genetics/157.3.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]

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