Montreal University. Canada: Mixing our genes through sex helps purge us of disease mutations. For decades, theories on the genetic advantage of sexual
reproduction had been put forward, but none had ever been proven in
humans, until now. Researchers at the University of Montreal and the
Sainte-Justine University Hospital Research Centre in Montreal, Canada
have just shown how humanity's predispositions to disease gradually
decrease the more we mix our genetic material together. This discovery
was finally made possible by the availability in recent years of
repositories of biological samples and genetic data from different
populations around the globe.
What we already knew
As humans procreate, generation after generation, the exchange of
genetic material between man and woman causes our species to evolve
little by little. Chromosomes from the mother and the father recombine
to create the chromosomes of their child (chromosomes are the larger
building blocks of genomes). Scientists have known for some time,
however, that the parents' genomes don't mix together in a uniform way.
Chromosomes recombine frequently in some segments of the genome, while
recombination is less frequent in others. These segments of
low-frequency recombination will eventually recombine like others do but
it will take many, many generations.
The findings
More specifically, the team of Canadian researchers led by Dr. Philip
Awadalla discovered the following: the segments of the human genome
that don't recombine as often as others also tend to carry a
significantly greater proportion of the more disease-enabling genetic
mutations*. Until chromosome recombination eventually occurs, these
segments accumulate more and more bad mutations. In other words, as far
as susceptibility to disease is concerned, our genetic material actually
worsens, before it gets better. Thankfully, disease-enabling mutations
are eventually shuffled off our genetic code through sexual
reproduction. “But since these mutations rest on less dynamic segments
of our genome, the process can potentially take many hundreds of
generations,” explains Dr. Awadalla.
Why these findings are significant
“This discovery gives us a better understanding of how we, as humans,
become more or less at risk of developing or contracting diseases,”
says Dr. Awadalla. It also tells scientists more precisely where to look
in the human genome to find disease-enabling mutations, he adds, which
should speed up the discovery and identification of mutations associated
with specific diseases. Researchers and health authorities will in turn
be able to apply this new information to develop more effective
treatments and prevention programs.
The science behind the findings
Dr. Awadalla and his team studied the sequenced genomes of hundreds
of individuals from Canada's CARTaGENE genetic data repository and the
multinational 1000 Genomes Project. They found that the proportion of
mutations associated with disease was significantly higher in low
recombining segments known as “coldspots” relative to highly recombining
regions, and that the bad mutations in these coldspots were generally
more damaging than the mutations in the highly recombining segments.
Through the 1000 Genomes and CARTaGENE programs, the team was able to
compare this phenomenon across four present-day population basins:
Africans, Asians, Europeans and Canadians of French descent. Each of
these genetic groups exhibit the above behaviour to varying degrees.
African individuals showed the smallest relative proportion of
disease-associated mutations on their genome's coldspots, with Western
Europeans showing the largest.
The complete scientific paper was published by Nature Genetics and can be found online at http://www.nature.com/articles/doi:10.1038/ng.3216.
Research partners
This study was made possible by the financial support of Fonds de la
Recherche en Santé du Québec (FRSQ), Genome Québec, Fonds Québécois de
la Recherche sur la Nature et les Technologies (FQRNT) and the Canadian
Partnership Against Cancer. The CARTaGENE biobank, of which Dr. Awadalla
is also the scientific director, receives funding from the Canadian
Partnership Against Cancer, Genome Québec, Genome Canada and the
Canadian Institutes of Health Research. Dr. Awadalla is also a Professor
of Medical and Population Genetics at the University of Montreal and at
the Ontario Institute for Cancer Research.
* Mutations, also called “variations”, happen naturally and are not
necessarily a cause for concern. They occur when genes get incorrectly
copied from one parent to the child or after many generations' exposure
to certain environmental factors. Some mutations are benign, some
beneficial. Bad mutations however can increase our risk of contracting
or developing debilitating or life-threatening diseases.