Here we report the application of high-density oligonucleotide array (DNA chip)-based analysis to determine the distant history of single nucleotide polymorphisms (SNPs) in current human populations. We analysed orthologues for 397 human SNP sites (identified in CEPH pedigrees from Amish, Venezuelan and Utah populations1) from 23 common chimpanzee, 19 pygmy chimpanzee and 11 gorilla genomic DNA samples. From this data we determined 214 proposed ancestral alleles (the sequence found in the last common ancestor of humans and chimpanzees). In a diverse human population set, we found that SNP alleles with higher frequencies were more likely to be ancestral than less frequently occurring alleles. There were, however, exceptions. We also found three shared human/pygmy chimpanzee polymorphisms, all involving CpG dinucleotides, and two shared human/gorilla polymorphisms, one involving a CpG dinucleotide. We demonstrate that microarray-based assays allow rapid comparative sequence analysis of intra- and interspecies genetic variation.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Wang, D.G. et al. Large-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome. Science 280, 1077–1082 (1998).
Ruvolo, M. A new approach to studying modern human origins: hypothesis testing with coalescence time distributions. Mol. Phylogenet. Evol. 5, 202–219 (1996).
Goodman, M. et al. Toward a phylogenetic classification of primates based on DNA evidence complemented by fossil evidence. Mol. Phylogenet. Evol. 9, 585–598 ( 1998).
Hacia, J.G. et al. Evolutionary sequence comparisons using high-density oligonucleotide arrays. Nature Genet. 18, 155– 158 (1998).
Savatier, P. et al. Evolution of the primate β-globin gene region. High rate of variation in CpG dinucleotides and in short repeated sequences between man and chimpanzee. J. Mol. Biol. 182, 21 –29 (1985).
Sved, J. & Bird, A. The expected equilibrium of the CpG dinucleotide in vertebrate genomes under a mutation model. Proc. Natl Acad. Sci. USA 12, 4692–4696 (1990).
Yang, A.S. et al. The rate of CpG mutation in Alu repetitive elements within the p53 tumor suppressor gene in the primate germline. J. Mol. Biol. 258, 240–250 ( 1996).
Watterson, G.A. & Guess, H.A. Is the most frequent allele the oldest? Theor. Popul. Biol. 11, 141–160 (1977).
Watkins, D.I. The evolution of major histocompatibility class I genes in primates. Crit. Rev. Immunol. 15, 1–29 (1995).
Brown, W.M., Prager, E.M., Wang, A. & Wilson, A.C. Mitochondrial DNA sequences of primates: tempo and mode of evolution. J. Mol. Evol. 18, 225–239 ( 1982).
Garner, K.J. & Ryder, O.A. Mitochondrial DNA diversity in gorillas. Mol. Phylogenet. Evol. 6, 39– 48 (1996).
Crouau-Roy, B., Service, S., Slatkin, M. & Freimer, N. A fine-scale comparison of the human and chimpanzee genomes: linkage, linkage disequilibrium and sequence analysis. Hum. Mol. Genet. 5, 1131– 1137 (1996).
Wise, C.A., Sraml, M., Rubinsztein, D.C. & Easteal, S. Comparative nuclear and mitochondrial genome diversity in humans and chimpanzees. Mol. Biol. Evol. 14, 707– 716 (1997).
Cooper, G., Rubinsztein, D.C. & Amos, W. Ascertainment bias cannot entirely account for human microsatellites being longer than their chimpanzee homologues. Hum. Mol. Genet. 7, 1425–1429 (1998).
Mountain, J.L. & Cavalli-Sforza, L.L. Inference of human evolution through cladistic analysis of nuclear DNA restriction polymorphisms. Proc. Natl Acad. Sci. USA 91, 6515– 6519 (1994).
Martinko, J.M., Vincek, V., Klein, D. & Klein, J. Primate ABO glycotransferases: evidence for trans-species evolution. Immunogenetics 37, 274–278 (1993).
Deeb, S.S., Jorgensen, A.L., Battisti, L., Iwasaki, L. & Motulsky, A.G. Sequence divergence of the red and green visual pigments in great apes and humans. Proc. Natl Acad. Sci. USA 91, 7262–7266 (1994).
Jaeger, E.E.M. et al. Characterization of chimpanzee TCRV gene polymorphism: how old are human TCRV alleles? Immunogenetics 47, 115–123 (1998).
Kimura, M. The Neutral Theory of Molecular Evolution (Cambridge University Press, Cambridge, 1983).
Bergstrom, T.F., Josefsson, A., Erlich, H.A. & Gyllensten, U. Recent origin of HLA-DRB1 alleles and implications for human evolution. Nature Genet. 18, 237– 242 (1998).
Clark, A.G. Neutral behavior of shared polymorphism. Proc. Natl Acad. Sci. USA 94, 7730–7734 ( 1997).
Chee, M.S. et al. Accessing genetic information with high-density DNA arrays. Science 274, 610–614 (1996).
Hacia, J.G. et al. Detection of heterozygous mutations in BRCA1 using high density oligonucleotide arrays and two-colour fluorescence analysis. Nature Genet. 14, 441– 447 (1996).
Morin, P.A. et al. Kin selection, social structure, gene flow, and the evolution of chimpanzees. Science 265, 1193– 1201 (1994).
Collins, F.S., Guyer, M.S. & Chakravarti, A. Variations on a theme: cataloging human DNA sequence variation. Science 278, 1580– 1581 (1997).
Kruglyak, L. The use of a genetic map of biallelic markers in linkage studies. Nature Genet. 17, 21–24 (1997).
Nickerson D.A. et al. DNA sequence diversity in a 9.7-kb region of the human lipoprotein lipase gene. Nature Genet. 19, 233– 240 (1998).
Lai, E., Riley, J., Purvis, I. & Roses, A. A 4-Mb high-density single nucleotide polymorphism-based map around human APOE. Genomics 54, 31–38 ( 1998).
We thank P.A. Morin for assistance in obtaining chimpanzee DNA samples. Partial support for this work was provided by 5POLHGO1323-03 (S.P.A.F.).
About this article
A homogeneous fluorescent biosensing strategy for highly sensitive detection of DNA based on a programmed entropy-driven strand displacement reaction and DNAzyme for dual recycling amplification
Analytical Methods (2019)
Biophysical, Biochemical, and Cell Based Approaches Used to Decipher the Role of Carbonic Anhydrases in Cancer and to Evaluate the Potency of Targeted Inhibitors
International Journal of Medicinal Chemistry (2018)
Electrochemical primer extension based on polyoxometalate electroactive labels for multiplexed detection of single nucleotide polymorphisms
Biosensors and Bioelectronics (2018)
Japanese Journal of Applied Physics (2018)