Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Jul 5;91(14):6364–6368. doi: 10.1073/pnas.91.14.6364

Nonneutral evolution at the mitochondrial NADH dehydrogenase subunit 3 gene in mice.

M W Nachman 1, S N Boyer 1, C F Aquadro 1
PMCID: PMC44202  PMID: 8022788

Abstract

The neutral theory of molecular evolution asserts that while many mutations are deleterious and rapidly eliminated from populations, those that we observe as polymorphisms within populations are functionally equivalent to each other and thus neutral with respect to fitness. Mitochondrial DNA (mtDNA) is widely used as a genetic marker in evolutionary studies and is generally assumed to evolve according to a strictly neutral model of molecular evolution. One prediction of the neutral theory is that the ratio of replacement (nonsynonymous) to silent (synonymous) nucleotide substitutions will be the same within and between species. We tested this prediction by measuring DNA sequence variation at the mitochondrially encoded NADH dehydrogenase subunit 3 (ND3) gene among 56 individual house mice, Mus domesticus. We also compared ND3 sequence from M. domesticus to ND3 sequence from Mus musculus and Mus spretus. A significantly greater number of replacement polymorphisms were observed within M. domesticus than expected based on comparisons to either M. musculus or M. spretus. This result challenges the conventional view that mtDNA evolves according to a strictly neutral model. However, this result is consistent with a nearly neutral model of molecular evolution and suggests that most amino acid polymorphisms at this gene may be slightly deleterious.

Full text

PDF
6364

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bibb M. J., Van Etten R. A., Wright C. T., Walberg M. W., Clayton D. A. Sequence and gene organization of mouse mitochondrial DNA. Cell. 1981 Oct;26(2 Pt 2):167–180. doi: 10.1016/0092-8674(81)90300-7. [DOI] [PubMed] [Google Scholar]
  2. Cann R. L., Stoneking M., Wilson A. C. Mitochondrial DNA and human evolution. Nature. 1987 Jan 1;325(6099):31–36. doi: 10.1038/325031a0. [DOI] [PubMed] [Google Scholar]
  3. Clark A. G. Natural selection with nuclear and cytoplasmic transmission. I. A deterministic model. Genetics. 1984 Aug;107(4):679–701. doi: 10.1093/genetics/107.4.679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Di Rienzo A., Wilson A. C. Branching pattern in the evolutionary tree for human mitochondrial DNA. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1597–1601. doi: 10.1073/pnas.88.5.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hudson R. R., Kaplan N. L. The coalescent process in models with selection and recombination. Genetics. 1988 Nov;120(3):831–840. doi: 10.1093/genetics/120.3.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hudson R. R., Slatkin M., Maddison W. P. Estimation of levels of gene flow from DNA sequence data. Genetics. 1992 Oct;132(2):583–589. doi: 10.1093/genetics/132.2.583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kaneko M., Satta Y., Matsuura E. T., Chigusa S. I. Evolution of the mitochondrial ATPase 6 gene in Drosophila: unusually high level of polymorphism in D. melanogaster. Genet Res. 1993 Jun;61(3):195–204. doi: 10.1017/s0016672300031360. [DOI] [PubMed] [Google Scholar]
  8. Kaplan N. L., Hudson R. R., Langley C. H. The "hitchhiking effect" revisited. Genetics. 1989 Dec;123(4):887–899. doi: 10.1093/genetics/123.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kimura M. A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol. 1980 Dec;16(2):111–120. doi: 10.1007/BF01731581. [DOI] [PubMed] [Google Scholar]
  10. Kocher T. D., Thomas W. K., Meyer A., Edwards S. V., Päbo S., Villablanca F. X., Wilson A. C. Dynamics of mitochondrial DNA evolution in animals: amplification and sequencing with conserved primers. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6196–6200. doi: 10.1073/pnas.86.16.6196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. MacRae A. F., Anderson W. W. Evidence for non-neutrality of mitochondrial DNA haplotypes in Drosophila pseudoobscura. Genetics. 1988 Oct;120(2):485–494. doi: 10.1093/genetics/120.2.485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McDonald J. H., Kreitman M. Adaptive protein evolution at the Adh locus in Drosophila. Nature. 1991 Jun 20;351(6328):652–654. doi: 10.1038/351652a0. [DOI] [PubMed] [Google Scholar]
  13. Nachman M. W., Boyer S. N., Searle J. B., Aquadro C. F. Mitochondrial DNA variation and the evolution of Robertsonian chromosomal races of house mice, Mus domesticus. Genetics. 1994 Mar;136(3):1105–1120. doi: 10.1093/genetics/136.3.1105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nigro L., Prout T. Is there selection on RFLP differences in mitochondrial DNA? Genetics. 1990 Jul;125(3):551–555. doi: 10.1093/genetics/125.3.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ohta T. Theoretical study of near neutrality. II. Effect of subdivided population structure with local extinction and recolonization. Genetics. 1992 Apr;130(4):917–923. doi: 10.1093/genetics/130.4.917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ruvolo M., Zehr S., von Dornum M., Pan D., Chang B., Lin J. Mitochondrial COII sequences and modern human origins. Mol Biol Evol. 1993 Nov;10(6):1115–1135. doi: 10.1093/oxfordjournals.molbev.a040068. [DOI] [PubMed] [Google Scholar]
  17. Saiki R. K., Gelfand D. H., Stoffel S., Scharf S. J., Higuchi R., Horn G. T., Mullis K. B., Erlich H. A. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. doi: 10.1126/science.2448875. [DOI] [PubMed] [Google Scholar]
  18. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sawyer S. A., Dykhuizen D. E., Hartl D. L. Confidence interval for the number of selectively neutral amino acid polymorphisms. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6225–6228. doi: 10.1073/pnas.84.17.6225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Sawyer S. A., Hartl D. L. Population genetics of polymorphism and divergence. Genetics. 1992 Dec;132(4):1161–1176. doi: 10.1093/genetics/132.4.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Singh R. S., Hale L. R. Are mitochondrial DNA variants selectively non-neutral? Genetics. 1990 Apr;124(4):995–997. doi: 10.1093/genetics/124.4.995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. doi: 10.1093/genetics/123.3.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Watterson G. A. The homozygosity test of neutrality. Genetics. 1978 Feb;88(2):405–417. doi: 10.1093/genetics/88.2.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Whittam T. S., Clark A. G., Stoneking M., Cann R. L., Wilson A. C. Allelic variation in human mitochondrial genes based on patterns of restriction site polymorphism. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9611–9615. doi: 10.1073/pnas.83.24.9611. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES