Title: Dynamics of mammalian chromosome evolution inferred from multispecies comparative maps

Slide set [PowerPoint]

Reading: 7/22/05 Science article by Murphy, Larkin, et al. [link]

Abstract: Comparative genome analysis in mammals has advanced significantly as a result of progress in genome mapping and DNA sequencing. We have studied the genome organization in eight phylogenetically distinct species to address fundamental questions relating to mammalian chromosomal evolution and to reconstruct ancestral mammalian chromosomes. Pairwise comparisons of the human genome sequence (NCBI build 33) with the sequence-based maps of two representative species of Rodentia (mouse, rat) were performed using the GRIMM-Synteny approach. In addition, comprehensive RH-based maps from representative species of three orders of mammals, Cetartiodactyla (pig, cattle), Carnivora (cat, dog), and Perissodactyla (horse), were included in the analysis.

The combined sequence and RH map-based analysis was conducted with a new bioinformatics tool that allowed for the visualization of homologous synteny blocks and lineage-specific or reuse breakpoints between the genomes analyzed. Identification of a significant number of reuse breakpoints confirms and extends our previous findings. These results provide a clear exception to the Nadeau-Taylor random breakpoint model of chromosome evolution. Analysis of gene content in and around evolutionary breakpoint regions revealed a marked enrichment in gene density compared to the genome-wide average, thus suggesting that at least some evolutionary breakpoints are acted upon by natural selection. Additionally, 98% of the primate-specific breakpoints contain segmental duplications that often flank inverted chromosomal segments. Analysis of centromeres and telomeres showed that significant numbers of telomere positions are conserved among mammalian species whereas centromeres have evolved more dynamically.

Association between the reuse evolutionary breakpoints and positions of centromeres implies that breakpoint reuse preferentially occurs at the sites of ancestral centromeres or neocentromeres in independent lineages. In contrast to previous findings, our analysis of chromosomal rearrangements in distinct mammalian species suggests an increase in the chromosomal breakage rate over the evolutionary time. This observation is supported by the remarkable similarity of ancestral genome architecture in reconstructed ferungulate and boreoeutherian ancestors. Also, we found an association between positions of cancer-associated chromosomal abnormalities in humans and the positions of evolutionary breakpoints, thus leading to the conclusion that some cancers may be a consequence of the same evolutionary mechanism that is necessary for speciation.

Bio: Denis Larkin is a visiting assistant professor in the Department of Animal Sciences, at the University of Illinois at Urban-Champaign. He is working on mapping and comparative analysis of the cattle genome, identification of cattle SNPs, and comparison of mammalian genomes.