New type of complex genetic variation discovered

Two University of Colorado School of Medicine scientists have discovered a previously unknown type of complex genetic variation. This unexpected finding might help explain how some organisms maintain high levels of diversity and can adapt rapidly to new stresses.

University of Colorado postdoctoral fellow Chris Todd Hittinger and Mark Johnston, chairman of the Department of Biochemistry and Molecular Genetics at the School of Medicine, and their collaborators at Vanderbilt University and Universidade Nova de Lisboa made the discovery. They identified a network of six genes that are wildly different in two populations of the same species of yeast, a close relative of the common baker's and brewer's yeast.

"This level of genetic divergence is expected between distantly related species, like human and mouse, but is unprecedented within a single species," Johnston said. "Most genes do not vary much between individuals because natural selection usually favors an optimal version of the gene, but sometimes no version is right for every situation. A well-known example in humans is a gene encoding a key component of hemoglobin: people in malaria-infested areas benefit from a form of the gene that provides resistance to malaria, but it can also cause sickle cell anemia."

The yeast's genes are responsible for its ability to eat galactose, a type of sugar found in milk and many fruits and legumes. A Portuguese population of the yeast has functional versions of all six genes and can use galactose; a Japanese population is unable to eat galactose because all six of those genes are riddled with mutations that make them nonfunctional. By comparing the genome sequences of every known strain of the species, the researchers found that the functional and nonfunctional versions of this gene network have existed for millions of years. Experiments in the lab revealed how strong natural selection could maintain high variation in this gene network, even though variation in other genes was limited.

"Lots of single-celled parasites, like those that cause sleeping sickness and malaria, have life cycles similar to yeast," Hittinger said. "They mostly reproduce asexually but occasionally mate and exchange genes. These are exactly the conditions we expect to allow for the maintenance of this type of complex genetic variation."

The study will be published online in the journal Nature.