DNA fingerprinting pioneer discovers role of key genetic catalyst for human diversity

Sep 05, 2010
This is Sir Alec Jeffreys of University of Leicester. Credit: University of Leicester

One of the key drivers of human evolution and diversity, accounting for changes that occur between different generations of people, is explained by new research published today by world-renowned scientist Professor Sir Alec Jeffreys, who discovered DNA fingerprinting at the University of Leicester.

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

Now, in a paper published online in (Sept 5), Sir Alec and his team in the Department of Genetics at the University of Leicester have demonstrated the remarkable influence of a particular gene on the development of diversity in humans.

The work was funded by the Medical Research Council, the Wellcome Trust, the Boehringer Ingelheim Fonds, the Royal Society and the Louis-Jeantet Foundation. Professor Jeffreys is Royal Society Wolfson Research Professor of Genetics at Leicester.

Sir Alec said: "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. 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."

Ironically, the variation in PRDM9 is due to a minisatellite within the gene itself. Sir Alec said: '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!'

Sir Alec believes the research, along with that of others working in the field, will inevitably further scientists' ability to understand the basic processes that make us all genetically unique, as well as defining an entirely new class of genetic risk factor for numerous disease-causing DNA rearrangements that can arise when recombination goes wrong.

These findings also provide a neat solution to one great puzzle of recombination hotspots - namely that they appear and disappear rapidly during evolution. Sir Alec said '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'.

Explore further: Researchers find new mechanism for neurodegeneration

More information: "PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans" by Jeffreys has been scheduled for Advance Online Publication (AOP) on Nature Genetics's website.

Related Stories

Sex Talk Revelations of the Lonely Y Chromosome

Sep 09, 2009

(PhysOrg.com) -- In the week that the University of Leicester celebrates the 25th anniversary of the discovery of DNA fingerprinting (Thursday September 10) new findings from the world-renowned University of Leicester Department ...

Zoo volunteers help explain mysteries of the genome

Sep 07, 2009

As we approache the 25th anniversary of the discovery of DNA fingerprinting (September 10), University of Leicester geneticists interested in a particular type of DNA are receiving some help from an unusual ...

Centromeres cross over, a lot

Jun 12, 2008

Recombination at centromeres is higher than anywhere else on the chromosome, even though methyltransferases do their best to prevent it, say Jaco et al., as published in the June 16 issue of the Journal of Cell Biology.

'Telepathic' genes recognize similarities in each other

Jan 24, 2008

Genes have the ability to recognise similarities in each other from a distance, without any proteins or other biological molecules aiding the process, according to new research published this week in the Journal of ...

Recommended for you

Researchers find new mechanism for neurodegeneration

15 hours ago

A research team led by Jackson Laboratory Professor and Howard Hughes Investigator Susan Ackerman, Ph.D., have pinpointed a surprising mechanism behind neurodegeneration in mice, one that involves a defect in a key component ...

Schizophrenia's genetic architecture revealed (w/ Video)

Jul 23, 2014

Queensland scientists are closer to effective treatments for schizophrenia after uncovering dozens of sites across the human genome that are strongly associated with a genetic predisposition to schizophrenia.

Mysterious esophagus disease is autoimmune after all

Jul 22, 2014

(Medical Xpress)—Achalasia is a rare disease – it affects 1 in 100,000 people – characterized by a loss of nerve cells in the esophageal wall. While its cause remains unknown, a new study by a team of researchers at ...

User comments : 0