A research team says they have discovered one of the key drivers of human evolution and diversity, accounting for changes that occur between different generations of people.

Professor Alec Jeffreys, who discovered DNA fingerprinting at the University of Leicester in 1984, and has spent the decades since investigating what he describes as "pretty bizarre bits of DNA" - highly variable repeated parts of DNA called 'minisatellites' - found in the human genome. Jeffreys observed that these seemed to be changing and "picking up mutations at an extraordinary rate" when compared to other DNA.

In a new Nature Genetics paper, researchers including Jeffreys describe the influence of a particular gene, PRDM9, on the development of diversity in humans. 

"In each generation our genetic make-up gets 'reshuffled', like a genetic pack of cards, by a process called recombination - a fundamental engine driving diversity," says Jeffreys. "The work we have done over the past 10 years at Leicester has been key to understanding recombination in humans, and has allowed the molecular definition of recombination 'hotspots' - small regions in which the reshuffling process is focused.

"Our new study has focused on a gene called PRDM9 that makes a protein which binds to DNA and triggers hotspot activity. The exciting finding is that people with different versions of PRDM9 show profoundly different recombination behaviours, not only in hotspots but also in chromosomal rearrangements that cause some genetic disorders."

The variation in PRDM9 is due to a minisatellite within the gene itself, says Jeffreys.  "I've come full circle – starting out with minisatellites to develop DNA fingerprinting, and arriving at a gene containing a minisatellite that plays a key role in driving all kinds of human DNA diversity, including variation at minisatellites. An intriguing possibility is that it is even driving its own evolution!"

Jeffreys says these findings also provide a solution to one great puzzle of recombination hotspots, namely that they appear and disappear rapidly during evolution. "We've shown that hotspots have a strange propensity for self-destruction, so how can they possibly exist? The PRDM9 minisatellite gives the answer – it evolves rapidly, like any other unstable minisatellite, and keeps churning out variants that can trigger new hotspots, replenishing those that have committed suicide. A totally crazy mechanism to ensure that recombination keeps going, but typical of the weird solutions that evolution can throw up."

The work was funded by the Medical Research Council, the Wellcome Trust, the Boehringer Ingelheim Fonds, the Royal Society and the Louis-Jeantet Foundation. 

Citation: Ingrid L Berg, Rita Neumann, Kwan-Wood G Lam, Shriparna Sarbajna, Linda Odenthal-Hesse, Celia A May, Alec J Jeffreys, 'PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans', Nature Genetics Published online: 5 September 2010 doi:10.1038/ng.658