Comparative cytogenetics of human chromosome 3q21.3 reveals a hot spot for ectopic recombination in hominoid evolution

doi:10.1016/j.ygeno.2004.10.007

Genomics

Volume 85, Issue 1, January 2005, Pages 36-47

https://doi.org/10.1016/j.ygeno.2004.10.007 Get rights and content

Abstract

Fluorescence in situ hybridization mapping of fully integrated human BAC clones to primate chromosomes, combined with precise breakpoint localization by PCR analysis of flow-sorted chromosomes, was used to analyze the evolutionary rearrangements of the human 3q21.3-syntenic region in orangutan, siamang gibbon, and silvered-leaf monkey. Three independent evolutionary breakpoints were localized within a 230-kb segment contained in BACs RP11-93K22 and RP11-77P16. Approximately 200 kb of the human 3q21.3 sequence was not present on the homologous orangutan, siamang, and Old World monkey chromosomes, suggesting a genomic DNA insertion into the breakpoint region in the lineage leading to humans and African great apes. The breakpoints in the orangutan and siamang genomes were narrowed down to 12- and 20-kb DNA segments, respectively, which are enriched with endogenous retrovirus long terminal repeats and other repetitive elements. The inserted DNA segment represents part of an ancestral duplication. Paralogous sequence blocks were found at human 3q21, approximately 4 Mb proximal to the evolutionary breakpoint cluster region; at human 3p12.3, which contains an independent orangutan-specific breakpoint; and at the subtelomeric and pericentromeric regions of multiple human and orangutan chromosomes. The evolutionary breakpoint regions between human chromosome 3 and orangutan 2 as well their paralogous segments in the human genome coincide with breaks of chromosomal synteny in the mouse, rat, and/or chicken genomes. Collectively our data reveal reuse of the same short recombinogenic DNA segments in primate and vertebrate evolution, supporting a nonrandom breakage model of genome evolution.

Section snippets

A 230-kb segment involved in independent chromosome rearrangements during hominoid evolution

Previously, we have demonstrated synteny conservation of four large chromosomal blocks (indicated by differently colored bars in Fig. 1A) between HSA 3 and Bornean PPY 2 [5]. One inversion breakpoint between the human and the orangutan chromosome forms was located in the interval between YACs 896G9 and 914H1 at 130–132 Mb in HSA 3q22.1. Because of higher resolution mapping of the breakpoint region in this study, the band position was changed to HSA 3q21.3. In the siamang gibbon, a breakpoint

Cell lines and DNA probes

Metaphase chromosomes were obtained from EBV-transformed lymphoblastoid cell lines of human, chimpanzee, Bornean × Sumatran orangutan hybrid, siamang gibbon, and silvered-leaf monkey following standard protocols. BAC clones were selected from the Wellcome Trust Sanger Institute Ensembl contigs (http:/www.ensembl.org) and obtained from the Resource Center Primary Database of the German Human Genome Project, the Children's Hospital Oakland–BACPAC Resources, and ResGen (Invitrogen Corp.). Genomic

Note added in proof

In the November 2004 version of the human genome sequence, the 3q21.3 breakpoint cluster region contains five hypothetical genes and two OR pseudogenes (Fig. 3A). OR pseudogenes are also found in all the 3q21.3-paralogous segments (Table 4).

Acknowledgments

We thank Patricia C.M. O'Brien and Beiyuan Fu for technical assistance in generating the chromosome-specific DNA libraries. This study was supported by the German Research Foundation (HA 1374/5-2) and the Boehringer Ingelheim Foundation.

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Comparative cytogenetics of human chromosome 3q21.3 reveals a hot spot for ectopic recombination in hominoid evolution

Abstract

Section snippets

A 230-kb segment involved in independent chromosome rearrangements during hominoid evolution

Cell lines and DNA probes

Note added in proof

Acknowledgments

Genomics

Am. J. Hum. Genet.

J. Mol. Biol.

Am. J. Hum. Genet.

Curr. Opin. Genet. Dev.

Cell

Genomics

Chromosomal evolution in primates: tentative phylogeny from Microcebus murinus (Prosimian) to man

Hum. Genet.

The origin of man: a chromosomal pictorial legacy

Science

Reconstruction of genomic rearrangements in great apes and gibbons by chromosome painting

Proc. Natl. Acad. Sci. USA

Emerging patterns of comparative genome organization in some mammalian species as revealed by Zoo-FISH

Genome Res.

Lengths of chromosome segments conserved since divergence of man and mouse

Proc. Natl. Acad. Sci. USA

Ancient linkage groups and frozen accidents

Nature