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Hotspots of mutation and breakage in dog and human chromosomes

Webber, Caleb and Ponting, Chris P. 2005. Hotspots of mutation and breakage in dog and human chromosomes. Genome Research 15 (12) , pp. 1787-1797. 10.1101/gr.3896805

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Abstract

Sequencing of the dog genome allows an investigation of the location-dependent evolutionary processes that occurred since the common ancestor of primates and carnivores, ∼95 million years ago. We investigated variations in G+C nucleotide fraction and synonymous nucleotide substitution rates (Ks) across dog and human genomes. Our results show that dog genes located either in subtelomeric and pericentromeric regions, or in short synteny blocks, possess significantly elevated G+C fraction and Ks values. Human subtelomeric, but not pericentromeric, genes also exhibit these elevations. We then examined 1.048 Gb of human sequence that is likely not to have been located near a primate telomere at any time since the common ancestor of dog and human. We observed that regions of highest G+C or Ks (“hotspots”; median sizes of 0.5 or 1.3 Mb, respectively) within this sequence were preferentially segregated to dog subtelomeres and pericentromeres during the rearrangements that eventually gave rise to the extant canine karyotype. Our data cannot be accounted for solely on the basis of gradually elevating G+C fractions in subtelomeric regions as a consequence of biased gene conversion. Rather, we propose that high G+C sequences are found preferentially within dog subtelomeres as a direct consequence of chromosomal fission occurring more frequently within regions elevated in G+C.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Cold Spring Harbor Laboratory Press
ISSN: 1088-9051
Date of First Compliant Deposit: 23 October 2020
Date of Acceptance: 16 June 2005
Last Modified: 23 Oct 2020 13:45
URI: http://orca-mwe.cf.ac.uk/id/eprint/135816

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