• 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. Nov 1998; 150(3): 1133–1141.
PMCID: PMC1460397

DNA variability and recombination rates at X-linked loci in humans.

Abstract

We sequenced 11,365 bp from introns of seven X-linked genes in 10 humans, one chimpanzee, and one orangutan to (i) provide an average estimate of nucleotide diversity (pi) in humans, (ii) investigate whether there is variation in pi among loci, (iii) compare ratios of polymorphism to divergence among loci, and (iv) provide a preliminary test of the hypothesis that heterozygosity is positively correlated with the local rate of recombination. The average value for pi was low 0.063%, SE = 0.036%, about one order of magnitude smaller than for Drosophila melanogaster, the species for which the best data are available. Among loci, pi varied by over one order of magnitude. Statistical tests of neutrality based on ratios of polymorphism to divergence or based on the frequency spectrum of variation within humans failed to reject a neutral, equilibrium model. However, there was a positive correlation between heterozygosity and rate of recombination, suggesting that the joint effects of selection and linkage are important in shaping patterns of nucleotide variation in humans.

Full Text

The Full Text of this article is available as a PDF (139K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Aquadro CF. Why is the genome variable? Insights from Drosophila. Trends Genet. 1992 Oct;8(10):355–362. [PubMed]
  • Aquadro CF. Insights into the evolutionary process from patterns of DNA sequence variability. Curr Opin Genet Dev. 1997 Dec;7(6):835–840. [PubMed]
  • Begun DJ, Aquadro CF. Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature. 1992 Apr 9;356(6369):519–520. [PubMed]
  • Begun DJ, Aquadro CF. African and North American populations of Drosophila melanogaster are very different at the DNA level. Nature. 1993 Oct 7;365(6446):548–550. [PubMed]
  • Bird AP. Gene number, noise reduction and biological complexity. Trends Genet. 1995 Mar;11(3):94–100. [PubMed]
  • Braverman JM, Hudson RR, Kaplan NL, Langley CH, Stephan W. The hitchhiking effect on the site frequency spectrum of DNA polymorphisms. Genetics. 1995 Jun;140(2):783–796. [PMC free article] [PubMed]
  • Charlesworth B. The effect of background selection against deleterious mutations on weakly selected, linked variants. Genet Res. 1994 Jun;63(3):213–227. [PubMed]
  • Charlesworth B, Morgan MT, Charlesworth D. The effect of deleterious mutations on neutral molecular variation. Genetics. 1993 Aug;134(4):1289–1303. [PMC free article] [PubMed]
  • Charlesworth D, Charlesworth B, Morgan MT. The pattern of neutral molecular variation under the background selection model. Genetics. 1995 Dec;141(4):1619–1632. [PMC free article] [PubMed]
  • Clark AG, Weiss KM, Nickerson DA, Taylor SL, Buchanan A, Stengård J, Salomaa V, Vartiainen E, Perola M, Boerwinkle E, et al. Haplotype structure and population genetic inferences from nucleotide-sequence variation in human lipoprotein lipase. Am J Hum Genet. 1998 Aug;63(2):595–612. [PMC free article] [PubMed]
  • Dib C, Fauré S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, et al. A comprehensive genetic map of the human genome based on 5,264 microsatellites. Nature. 1996 Mar 14;380(6570):152–154. [PubMed]
  • Diehl HJ, Schaich M, Budzinski RM, Stoffel W. Individual exons encode the integral membrane domains of human myelin proteolipid protein. Proc Natl Acad Sci U S A. 1986 Dec;83(24):9807–9811. [PMC free article] [PubMed]
  • Dorit RL, Akashi H, Gilbert W. Absence of polymorphism at the ZFY locus on the human Y chromosome. Science. 1995 May 26;268(5214):1183–1185. [PubMed]
  • Drake JW, Charlesworth B, Charlesworth D, Crow JF. Rates of spontaneous mutation. Genetics. 1998 Apr;148(4):1667–1686. [PMC free article] [PubMed]
  • Edwards A, Voss H, Rice P, Civitello A, Stegemann J, Schwager C, Zimmermann J, Erfle H, Caskey CT, Ansorge W. Automated DNA sequencing of the human HPRT locus. Genomics. 1990 Apr;6(4):593–608. [PubMed]
  • Excoffier L. Evolution of human mitochondrial DNA: evidence for departure from a pure neutral model of populations at equilibrium. J Mol Evol. 1990 Feb;30(2):125–139. [PubMed]
  • Fu YX. Estimating the age of the common ancestor of a DNA sample using the number of segregating sites. Genetics. 1996 Oct;144(2):829–838. [PMC free article] [PubMed]
  • Fu YX, Li WH. Statistical tests of neutrality of mutations. Genetics. 1993 Mar;133(3):693–709. [PMC free article] [PubMed]
  • Nachman MW, Brown WM, Stoneking M, Aquadro CF. Nonneutral mitochondrial DNA variation in humans and chimpanzees. Genetics. 1996 Mar;142(3):953–963. [PMC free article] [PubMed]
  • Nagaraja R, MacMillan S, Kere J, Jones C, Griffin S, Schmatz M, Terrell J, Shomaker M, Jermak C, Hott C, et al. X chromosome map at 75-kb STS resolution, revealing extremes of recombination and GC content. Genome Res. 1997 Mar;7(3):210–222. [PubMed]
  • Fullerton SM, Harding RM, Boyce AJ, Clegg JB. Molecular and population genetic analysis of allelic sequence diversity at the human beta-globin locus. Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1805–1809. [PMC free article] [PubMed]
  • Nei M, Li WH. Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5269–5273. [PMC free article] [PubMed]
  • Guo W, Worley K, Adams V, Mason J, Sylvester-Jackson D, Zhang YH, Towbin JA, Fogt DD, Madu S, Wheeler DA, et al. Genomic scanning for expressed sequences in Xp21 identifies the glycerol kinase gene. Nat Genet. 1993 Aug;4(4):367–372. [PubMed]
  • Nickerson DA, Taylor SL, Weiss KM, Clark AG, Hutchinson RG, Stengård J, Salomaa V, Vartiainen E, Boerwinkle E, Sing CF. DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nat Genet. 1998 Jul;19(3):233–240. [PubMed]
  • Hammer MF. A recent common ancestry for human Y chromosomes. Nature. 1995 Nov 23;378(6555):376–378. [PubMed]
  • Noguchi M, Adelstein S, Cao X, Leonard WJ. Characterization of the human interleukin-2 receptor gamma chain gene. J Biol Chem. 1993 Jun 25;268(18):13601–13608. [PubMed]
  • Harding RM, Fullerton SM, Griffiths RC, Bond J, Cox MJ, Schneider JA, Moulin DS, Clegg JB. Archaic African and Asian lineages in the genetic ancestry of modern humans. Am J Hum Genet. 1997 Apr;60(4):772–789. [PMC free article] [PubMed]
  • Oudet C, Hanauer A, Clemens P, Caskey T, Mandel JL. Two hot spots of recombination in the DMD gene correlate with the deletion prone regions. Hum Mol Genet. 1992 Nov;1(8):599–603. [PubMed]
  • Hey J. Mitochondrial and nuclear genes present conflicting portraits of human origins. Mol Biol Evol. 1997 Feb;14(2):166–172. [PubMed]
  • Hey J, Wakeley J. A coalescent estimator of the population recombination rate. Genetics. 1997 Mar;145(3):833–846. [PMC free article] [PubMed]
  • Roest Crollius H, Ross MT, Grigoriev A, Knights CJ, Holloway E, Misfud J, Li K, Playford M, Gregory SG, Humphray SJ, et al. An integrated YAC map of the human X chromosome. Genome Res. 1996 Oct;6(10):943–955. [PubMed]
  • Huang W, Fu YX, Chang BH, Gu X, Jorde LB, Li WH. Sequence variation in ZFX introns in human populations. Mol Biol Evol. 1998 Feb;15(2):138–142. [PubMed]
  • Roest Crollius H, Ross MT, Grigoriev A, Knights CJ, Holloway E, Misfud J, Li K, Playford M, Gregory SG, Humphray SJ, et al. An integrated YAC map of the human X chromosome. Genome Res. 1996 Oct;6(10):943–955. [PubMed]
  • Saiki RK, Gelfand DH, Stoffel S, Scharf SJ, Higuchi R, Horn GT, Mullis KB, Erlich HA. Primer-directed enzymatic amplification of DNA with a thermostable DNA polymerase. Science. 1988 Jan 29;239(4839):487–491. [PubMed]
  • Hudson RR. How can the low levels of DNA sequence variation in regions of the drosophila genome with low recombination rates be explained? Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6815–6818. [PMC free article] [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Hudson RR, Kaplan NL. Deleterious background selection with recombination. Genetics. 1995 Dec;141(4):1605–1617. [PMC free article] [PubMed]
  • Schaeffer SW, Miller EL. Estimates of linkage disequilibrium and the recombination parameter determined from segregating nucleotide sites in the alcohol dehydrogenase region of Drosophila pseudoobscura. Genetics. 1993 Oct;135(2):541–552. [PMC free article] [PubMed]
  • Hudson RR, Kaplan NL. Deleterious background selection with recombination. Genetics. 1995 Dec;141(4):1605–1617. [PMC free article] [PubMed]
  • Hudson RR, Kreitman M, Aguadé M. A test of neutral molecular evolution based on nucleotide data. Genetics. 1987 May;116(1):153–159. [PMC free article] [PubMed]
  • Simonsen KL, Churchill GA, Aquadro CF. Properties of statistical tests of neutrality for DNA polymorphism data. Genetics. 1995 Sep;141(1):413–429. [PMC free article] [PubMed]
  • Kaplan NL, Hudson RR, Langley CH. The "hitchhiking effect" revisited. Genetics. 1989 Dec;123(4):887–899. [PMC free article] [PubMed]
  • Koike K, Urata Y, Matsuo S, Koike M. Characterization and nucleotide sequence of the gene encoding the human pyruvate dehydrogenase alpha-subunit. Gene. 1990 Sep 14;93(2):307–311. [PubMed]
  • Kreitman M. Nucleotide polymorphism at the alcohol dehydrogenase locus of Drosophila melanogaster. Nature. 1983 Aug 4;304(5925):412–417. [PubMed]
  • Stephan W. An improved method for estimating the rate of fixation of favorable mutations based on DNA polymorphism data. Mol Biol Evol. 1995 Sep;12(5):959–962. [PubMed]
  • Tajima F. Evolutionary relationship of DNA sequences in finite populations. Genetics. 1983 Oct;105(2):437–460. [PMC free article] [PubMed]
  • Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. [PMC free article] [PubMed]
  • Wang LH, Collins A, Lawrence S, Keats BJ, Morton NE. Integration of gene maps: chromosome X. Genomics. 1994 Aug;22(3):590–604. [PubMed]
  • Watterson GA. On the number of segregating sites in genetical models without recombination. Theor Popul Biol. 1975 Apr;7(2):256–276. [PubMed]
  • Whitfield LS, Sulston JE, Goodfellow PN. Sequence variation of the human Y chromosome. Nature. 1995 Nov 23;378(6555):379–380. [PubMed]
  • McDonald JH, Kreitman M. Adaptive protein evolution at the Adh locus in Drosophila. Nature. 1991 Jun 20;351(6328):652–654. [PubMed]
  • Whittam TS, Clark AG, Stoneking M, Cann RL, Wilson AC. 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. [PMC free article] [PubMed]
  • McVean GT, Hurst LD. Evidence for a selectively favourable reduction in the mutation rate of the X chromosome. Nature. 1997 Mar 27;386(6623):388–392. [PubMed]
  • Wiehe TH, Stephan W. Analysis of a genetic hitchhiking model, and its application to DNA polymorphism data from Drosophila melanogaster. Mol Biol Evol. 1993 Jul;10(4):842–854. [PubMed]
  • Moriyama EN, Powell JR. Intraspecific nuclear DNA variation in Drosophila. Mol Biol Evol. 1996 Jan;13(1):261–277. [PubMed]
  • Nachman MW. Patterns of DNA variability at X-linked loci in Mus domesticus. Genetics. 1997 Nov;147(3):1303–1316. [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...