Family genetic research reveals the speed of human mutation

"Your genome, or genetic code, is made up of six billion pieces of information, called nucleotides," explained co-lead author Philip Awadalla of the University of Montreal's Faculty of Medicine and Director of CARTaGENE. "Three billion come from each parent, and based on indirect evolutionary studies, we had previously estimated that parents would contribute an average of 100-200 mistakes in these pieces of information to their child. Our genetic study, the first of its kind, shows that actually much fewer mistakes -- or mutations -- are made." Awadalla published the study with co-author Matt Hurles of the Wellcome Trust Sanger Institute in Nature Genetics on June 12, 2011.

As mutations play a key role in the evolutionary process, geneticists will now revise the number of generations separating us from genetic relatives such as apes. "In principle, evolution is happening a third as slowly as previously thought," Awadalla said. The researchers made the discovery by looking at the complete genomes of two families -- a mother, father and their child. In another first, the findings enabled the team to determine whether men contribute more mutations to their offspring than women. The theory is that because mistakes are made during cell division and DNA replication, and males produces many millions more gametes (sperm) than women (eggs), more mutations would come from men compared to women. In one of their families, men contributed six times as many genetic errors to their children.

However, the research also showed a wide variation between families. "We saw that the number of mutations from the male was less than the number of mutations from the female in one of the families," Awadalla explained. "This doesn't mean that we're throwing the theory out the window, it simply means that the mutation rate is extremely variable from individual to individual, or even that some people have mechanisms that reduce the likelihood of mutations." He also noted that this finding would have important implications for research that attempts to tie specific genetic mutations to diseases.

Researchers will need to undertake further studies with more families to better understand just how variable the individual mutation rate is. "We also need to be looking at other kinds of mutations, such as structural variations within our genetic code," Awadalla said.

The research was financed by the Wellcome Trust, Genome Quebec, and the Ministère du Développement économique, de l'Innovation et de l'Exportation of Quebec. The University of Montreal is officially known as Université de Montréal.