Abstract
Natural selection has been theoretically and empirically proven to alter patterns of linkage disequilibrium (LD). Reciprocally, recombination, the driving force behind LD, modifies the signature of natural selection by reintroducing variation in a punctuate manner across the genome. To date, efforts to identify genes that have been subjected to historical selective pressure by examining polymorphic variation and allelic association have frequently fallen short of unambiguously distinguishing selection from other biological mechanisms. Contemporary genetic maps that describe LD in fine detail represent a much needed tool that can be exploited by researchers aiming to tease apart these opposing signals.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Kimura, M. (1968) Evolutionary rate at the molecular level. Nature 217, 624–626.
Crow, J. F. and Kimura, M. (1970) An Introduction to Population Genetics Theory. Harper and Row, New York.
Holmquist, R., Jukes, T. H., and Pangburn, S. (1973) Evolution of transfer RNA. J. Mol. Biol. 78, 91–116.
Kimura, M. and Ota, T. (1973) Mutation and evolution at the molecular level. Genetics 73, 19–35.
Haldane, J. (1927) A mathematical theory of natural and artificial selection. Part V. Selection and mutation. Proc. Camb. Phil. Soc. 23, 838–844.
Weatherall, D. J., Miller, L. H., Baruch, D. I., et al. (2002) Malaria and the red cell. Hematology (Am Soc Hematol Educ Program) 1, 35–57.
Simoons, F. J. (1969) Primary adult lactose intolerance and the milking habit: a problem in biological and cultural interrelations. I. Review of the medical research. Am. J. Dig. Dis. 14, 819–836.
Bersaglieri, T., Sabeti, P. C., Patterson, N., et al. (2004) Genetic signatures of strong recent positive selection at the lactase gene. Am. J. Hum. Genet. 74, 1111–1120.
Jukes, T. H. and King, J. L. (1975) Evolutionary loss of ascorbic acid synthesizing ability. J. Hum. Evol. 4, 85–88.
Nandi, A., Mukhopadhyay, C. K., Ghosh, M. K., Chattopadhyay, D. J., and Chatterjee, I. B. (1997) Evolutionary significance of vitamin C biosynthesis in terrestrial vertebrates. Free Radic. Biol. Med. 22, 1047–1054.
Wang, X., Thomas, S. D., and Zhang, J. (2004) Relaxation of selective constraint and loss of function in the evolution of human bitter taste receptor genes. Hum. Mol. Genet. 13, 2671–2678.
Soranzo, N., Bufe, B., Sabeti, P. C., et al. (2005) Positive selection on a high-sensitivity allele of the human bitter-taste receptor TAS2R16. Curr. Biol. 15, 1257–1265.
Tajima, F. (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123, 585–595.
Taylor, M. F., Shen, Y., and Kreitman, M. E. (1995) A population genetic test of selection at the molecular level. Science 270, 1497–1499.
Fu, Y. X. and Li, W. H. (1993) Statistical tests of neutrality of mutations. Genetics 133, 693–709.
Hudson, R. R., Kreitman, M., and Aguade, M. (1987) A test of neutral molecular evolution based on nucleotide data. Genetics 116, 153–159.
McDonald, J. H. and Kreitman, M. (1991) Adaptive protein evolution at the Adh locus in Drosophila. Nature 351, 652–654.
Kreitman, M. (2000) Methods to detect selection in populations with applications to the human. Annu. Rev. Genomics Hum. Genet. 1, 539–659.
Nielsen, R. (2005) Molecular signatures of natural selection. Annu. Rev. Genet. 39, 197–218.
Carrington, M., Kissner, T., Gerrard, B., Ivanov, S., O’Brien, S. J., and Dean, M. (1997) Novel alleles of the chemokine-receptor gene CCR5. Am. J. Hum. Genet. 61, 1261–1267.
Stephens, J. C., Reich, D. E., Goldstein, D. B., et al. (1998) Dating the origin of the CCR5-Delta32 AIDS-resistance allele by the coalescence of haplotypes. Am. J. Hum. Genet. 62, 1507–1515.
Sabeti, P. C., Walsh, E., Schaffner, S. F., et al. (2005) The case for selection at CCR5-Delta32. PLoS Biol. 3, e378.
Kreitman, M. and Di Rienzo, A. (2004) Balancing claims for balancing selection. Trends Genet. 20, 300–304.
Smith, J. M. and Haigh, J. (1974) The hitch-hiking effect of a favourable gene. Genet. Res. 23, 23–35.
Tapper, W., Collins, A., Gibson, J., Maniatis, N., Ennis, S., and Morton, N. E. (2005) A map of the human genome in linkage disequilibrium units. Proc. Natl. Acad. Sci. USA 102, 11,835–11,839.
Sabeti, P. C., Reich, D. E., Higgins, J. M., et al. (2002) Detecting recent positive selection in the human genome from haplotype structure. Nature 419, 832–837.
Ruwende, C. and Hill, A. (1998) Glucose-6-phosphate dehydrogenase deficiency and malaria. J. Mol. Med. 76, 581–588.
Nei, M. (1987) Equation 8.4. Molecular Evolutionary Genetics. Columbia University Press, New York, NY.
Tishkoff, S. A., Varkonyi, R., Cahinhinan, N., et al. (2001) Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance. Science 293, 455–462.
Wang, E. T., Kodama, G., Baldi, P., and Moyzis, R. K. (2006) Global landscape of recent inferred Darwinian selection for Homo sapiens. Proc. Natl. Acad. Sci. USA 103, 135–140.
Serre, D., Nadon, R., and Hudson, T. J. (2005) Large-scale recombination rate patterns are conserved among human populations. Genome Res. 15, 1547–1552.
Stefansson, H., Helgason, A., Thorleifsson, G., et al. (2005) A common inversion under selection in Europeans. Nat. Genet. 37, 129–137.
Przeworski, M., Coop, G., and Wall, J. D. (2005) The signature of positive selection on standing genetic variation. Evolution Int. J. Org. Evolution 59, 2312–2323.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc.
About this protocol
Cite this protocol
Ennis, S. (2007). Linkage Disequilibrium as a Tool for Detecting Signatures of Natural Selection. In: Collins, A.R. (eds) Linkage Disequilibrium and Association Mapping. Methods in Molecular Biology™, vol 376. Humana Press. https://doi.org/10.1007/978-1-59745-389-9_5
Download citation
DOI: https://doi.org/10.1007/978-1-59745-389-9_5
Publisher Name: Humana Press
Print ISBN: 978-1-58829-669-6
Online ISBN: 978-1-59745-389-9
eBook Packages: Springer Protocols