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Exceptional Chromosome Regions Workshop I

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One Origin of Man: Primate Evolution Through Genome Duplication

Julie R. Korenberg, Xiao-Ning Chen, Steve Mitchell, Rajesh Puri, Zheng-Yang Shi and Dean Yimlamai
Medical Genetics Birth Defects Center, The CSMC Burns & Allen Research nstitute, UCLA School of Medicine, Los Angeles, CA

Chromosome duplication is a force that drives evolution. We now suggest that this may also be true of the primates and that the resulting duplications in part determine the spectrum of human chromosomal rearrangements. To investigate the existence and origin of duplications in the human genome, and their consequences, 5,000 bacterial artificial chromosomes (BACs) were mapped at 2-5 Mb resolution on human high resolution chromosomes by using fluorescence in situ hybridization. A subset of 469 of these was defined that generated two or more signals, excluding those located in regions of known repeated sequences, viz., the regions of centromeres, telomeres and ribosomal genes. Although a subset of these multiple site BACs represent the chimeric artifacts of cloning, derived from two different chromosomal regions, others reflect regions of true homology in the human genome.

Two questions were considered; first, the extent to which the multiple sites of hybridization of single BACs within single chromosomes reflected the breakpoints of naturally occurring human inversions, and second, the extent to which these same multiple hybridization points reflected the chromosomal inversion points in primate evolution. For human inversions, the results of the analyses revealed a total of 124 BACs (2.5%) mapping to two or more sites on the same chromosome, of which 81 (65%) mapped to one of 27 distinct human inversion sites, the largest share of which recognized the well-established pericentromeric inversions of chromosomes 1, 2, 9, and 18, as well as the paracentric inverted region of chromosome 7q11/q22. From this, we infer that meiotic mispairing involving the homologous regions may be responsible for the inversions.

With respect to primate evolution, a significant proportion of inversion breakpoints that characterize the chromosomal changes seen in the evolution of the great apes through man, are also reflected in the distribution of BAC multiple intrachromosomal sites. Further analyses of the 29 independent BACs recognizing the pericentromeric region of human chromosome 9 suggest at least three classes, two of which recognize only single sites in Pan troglodytes.

These data suggest that inversions occurring through primate evolution may generate small duplications that, although they can cause chromosomal imbalance in single individuals, they also provide the additional genetic material for speciation.


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