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Dichotomy of single-nucleotide polymorphism haplotypes in olfactory receptor genes and pseudogenes

Nature Genetics volume 26, pages 221–224 (2000)Cite this article

Abstract

Substantial efforts are focused on identifying single-nucleotide polymorphisms (SNPs) throughout the human genome, particularly in coding regions (cSNPs), for both linkage disequilibrium and association studies1,2. Less attention, however, has been directed to the clarification of evolutionary processes that are responsible for the variability in nucleotide diversity among different regions of the genome3. We report here the population sequence diversity of genomic segments within a 450-kb cluster4,5 of olfactory receptor (OR) genes6,7 on human chromosome 17. We found a dichotomy in the pattern of nucleotide diversity between OR pseudogenes and introns on the one hand and the closely interspersed intact genes on the other. We suggest that weak positive selection is responsible for the observed patterns of genetic variation. This is inferred from a lower ratio of polymorphism to divergence in genes compared with pseudogenes or introns, high non-synonymous substitution rates in OR genes, and a small but significant overall reduction in variability in the entire OR gene cluster compared with other genomic regions. The dichotomy among functionally different segments within a short genomic distance requires high recombination rates within this OR cluster. Our work demonstrates the impact of weak positive selection on human nucleotide diversity, and has implications for the evolution of the olfactory repertoire.

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Figure 1: The olfactory receptor gene cluster on human chromosome 17p13.3.
Figure 2: Allelic haplotypes of OR genes and pseudogenes.

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Acknowledgements

We thank U. Eisenstein for programming and B.-S. Boneh-Tamir for DNA samples. This research was supported by grants to D.L. from US National Institute of Health (DC00305), an Infrastructure grant of the Israel Ministry of Science, the German-Israel Foundation for Research and Development and the Krupp Foundation. And by the Israel Academy of Sciences-FIRST award to K.L.S. D.L. holds the Ralph and Lois Silver Chair in Human Genomics.

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  1. Dror Sharon

    Present address: Ocular Molecular Genetics Lab, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA

Authors and Affiliations

  1. Department of Molecular Genetics and the Crown Human Genome Center, The Weizmann Institute of Science, Rehovot, Israel

    Yoav Gilad, Daniel Segré, Doron Lancet & Dror Sharon

  2. Molecular Medicine Laboratory and Department of Nephrology, Faculty of Medicine, Technion-Israel Institute of Technology, Bat-Galim, Haifa, Israel

    Karl Skorecki

  3. Department of Ecology and Evolutionary Biology, BioSciences West Bldg., University of Arizona, Tucson, Arizona, USA

    Michael W. Nachman

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Correspondence to Doron Lancet.

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Gilad, Y., Segré, D., Skorecki, K. et al. Dichotomy of single-nucleotide polymorphism haplotypes in olfactory receptor genes and pseudogenes. Nat Genet 26, 221–224 (2000). https://doi.org/10.1038/79957

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