Origins of chromosomal rearrangement hotspots in the human genome: evidence from the AZFa deletion hotspots.
BACKGROUND
The origins of the recombination hotspots that are a common feature of both allelic and non-allelic homologous recombination in the human genome are poorly understood. We have investigated, by comparative sequencing, the evolution of two hotspots of non-allelic homologous recombination on the Y chromosome that lie within paralogous sequences known to sponsor deletions resulting in male infertility.


RESULTS
These recombination hotspots are characterized by signatures of concerted evolution, which indicate that gene conversion between paralogs has been predominant in shaping their recent evolution. By contrast, the paralogous sequences that surround the hotspots exhibit little evidence of gene conversion. A second feature of these rearrangement hotspots is the extreme interspecific sequence divergence (around 2.5%) that places them among the most divergent orthologous sequences between humans and chimpanzees.


CONCLUSIONS
Several hominid-specific gene conversion events have rendered these hotspots better substrates for chromosomal rearrangements in humans than in chimpanzees or gorillas. Monte Carlo simulations of sequence evolution suggest that extreme sequence divergence is a direct consequence of gene conversion between paralogs. We propose that the coincidence of signatures of concerted evolution and recurrent breakpoints of chromosomal rearrangement (mapped at the sequence level) may enable the identification of putative rearrangement hotspots from analysis of comparative sequences from great apes.
Molecular Genetics Laboratory, McDonald Institute for Archaeological Research, University of Cambridge, Downing Street, Cambridge, CB2 3ER, UK. meh@sanger.ac.uk
Matthew E
ME
Hurles
David
D
Willey
Lucy
L
Matthews
Syed Sufyan
SS
Hussain
D000483:Alleles; D000818:Animals; D002872:Chromosome Deletion; D041322:Chromosomes, Human, Y / Q000235:genetics*; D019143:Evolution, Molecular; D005785:Gene Conversion / Q000235:genetics*; D020440:Gene Duplication; D056426:Genetic Loci; D015894:Genome, Human; D006071:Gorilla gorilla / Q000235:genetics; D006801:Humans; D008297:Male; D009010:Monte Carlo Method; D002679:Pan troglodytes / Q000235:genetics; D029589:Seminal Plasma Proteins / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D014998:Y Chromosome / Q000235:genetics
D029589:Seminal Plasma Proteins