title: Assessing DNA sequence variations in human ESTs in a phylogenetic context using high-density oligonucleotide arrays.
abstract: We have analyzed human genomic diversity in 32 individuals representing four continental populations of Homo sapiens in the context of four ape species. We used DNA resequencing chips covering 898 expressed sequence tags (ESTs), corresponding to 109 kb of sequence. Based on the intra-species data, the neutral hypothesis could not be rejected. However, the mutation rate was two times lower than typically observed in functionally unconstrained genomic segments, suggesting a certain level of selection. The worldwide diversity (297 segregating sites and nucleotide diversity of 0.054%) was partitioned among continents, with the greatest amount of variation observed in the African sample. The long-term effective population size of the human population was estimated at 13,000; a similar figure was obtained for the African sample and a 20% lower estimate was obtained for the other continents. Africans also differed in having a higher number of continental-specific polymorphisms contributing to the higher average nucleotide diversity. These results are consistent with the existence of two distinct lineages of modern humans: amalgamation of these lineages in Africa led to the higher present-day diversity on that continent, whereas colonization of other continents by one of them gave the effect of a population bottleneck.
authors.affiliation: Affymetrix, Inc. 3380 Central Expressway, Santa Clara, California 95051, USA.
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.forename: Dominik
authors.initials: D
authors.lastname: Gehl
authors.forename: Linda
authors.initials: L
authors.lastname: Hsie
authors.forename: Naiping
authors.initials: N
authors.lastname: Shen
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lindblad-Toh
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Laviolette
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Robinson
authors.forename: Rob
authors.initials: R
authors.lastname: Lipshutz
authors.forename: David
authors.initials: D
authors.lastname: Wang
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Hudson
authors.forename: Damian
authors.initials: D
authors.lastname: Labuda
mesh_terms: D000818:Animals; D003627:Data Interpretation, Statistical; D020224:Expressed Sequence Tags; D014644:Genetic Variation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011323:Primates / Q000235:genetics; D017422:Sequence Analysis, DNA