Recombination ‘hotspots' and their evolution in the human genome


Research carried out at the University of Oxford has led to insights into the phenomenon of recombination ‘hotspots' and their rapid evolution in the human genome. The research was carried out at the Wellcome Trust Centre for Human Genetics (WTCHG) and Department of Statistics, and published in Science Express.

WTCHG researchers built on their earlier discovery of a DNA motif enriched at hotspots, which appears to form a key part of the genetic code for hotspot location. Combining bioinformatic approaches with the analysis of chimpanzee genetic variation data they identified a unique protein, PRDM9, predicted to bind the motif and hence to initiate recombination at motif locations, and whose role in recombination is supported by a host of additional data from mouse experiments.

PRDM9 has evolved exceptionally rapidly between humans and chimpanzees and this rapid evolution explains a second, previously published, finding of the researchers: recombination hotspots also differ between humans and chimpanzees. Remarkably, PRDM9 is involved not just in determining mouse hotspot locations, but is also a key player in mouse speciation.

Together with mutation, recombination is the fundamental biological process responsible for producing the genetic diversity we see in many species, including humans. Recombination shuffles genetic variation to produce new, potentially useful, varieties in the population. In human, recombination is an essential component of meiosis, the process generating sperm or egg cells. Despite its overwhelmingly positive role, errors in recombination can also occur. Such errors, occurring at specific genomic locations, are known to cause many human disorders by deleting, duplicating or inverting segments of the genome.

Although previous work has shown that recombination events are not randomly distributed in the genome, but cluster at specific ‘hotspot' sites, the biological factors responsible for these hotspots have remained undetermined.

Understanding the rapid evolution of PRDM9, its biological properties, and whether it has a more general role in driving speciation events, will be key focuses for future research.

Recombination hotspots


The zinc-finger protein PRDM9 was identified as a candidate hot-spot regulator from its predicted DNA-binding specificity: A the 13 base hotspot motif identified from human variation data; B the predicted binding specificity of PRDM9, a protein with 13 zinc fingers.









Drive Against Hotspot Motifs in Primates Implicates the PRDM9 Gene in Meiotic Recombination
Simon Myers, Rory Bowden, Afidalina Tumian, Ronald E. Bontrop, Colin Freeman, Tammie S. MacFie, Gil McVean, and Peter Donnelly
Published online December 31 2009 (Science Express Reports)

For more information on Prof Donnelly's research, click here.