People don’t need a full set of working genes to lead healthy lives, a new study shows. People can dispense with at least one active copy of 100 genes and get by without about 20 genes entirely.
Many genetic diseases result from mutations or genetic variants that inactivate genes. Such variants are called loss-of-function variants and were thought to be rare. But as scientists began compiling complete genetic profiles of thousands of people, it became clear that many genes might be dispensable.
This plethora of inactivated genes may make it difficult for scientists to track down disease-causing mutations in people with genetic disorders. But the new study provides some guidelines for telling likely disease-causing variants from benign ones.
Daniel MacArthur, while working at the Wellcome Trust Sanger Institute in Hinxton, England, and his colleagues examined complete genetic blueprints from 185 people who were part of the 1000 Genomes Project, an effort to catalog genetic diversity among people. MacArthur’s team found 1,285 gene-inactivating variants among the volunteers’ DNA. Each person’s DNA carried variants that inactivate at least one of the two copies of about 100 genes, with different genes affected in each individual. On average, people of European descent have about 20 completely inactivated genes, the team reports in the Feb. 17 Science.
The researchers also found that some genes get knocked out more often than others. “They tend to be genes that do not play a major, super-important role in our survival,” says Lluis Quintana-Murci, a population geneticist at the Pasteur Institute in Paris. Many of the frequently hit genes are involved in processes such as detecting smells, or affect how blood type is determined, how muscles work or how the body metabolizes drugs. The researchers found 250 genes in which both copies were shut down in at least one person, indicating those genes aren’t essential for survival.
Previous research has found that long stretches of DNA carrying several genes can be missing from people, and a pilot study from the 1000 Genomes Project estimated that people carry many more inactivated genes. This study counts only variants that are certain to disrupt genes. Quintana-Murci says many other variants not found in this study may also shut down genes.
Easily lost genes may be on the way out, evolutionarily. In nearly 43 percent of people in the study, at least one copy of a gene called VWDE is inactive, perhaps indicating it is on its last evolutionary legs.
Most of the gene-inactivating variants were rare, found in less than 2 percent of people in the study. More than 40 of the rare variants are known to be involved in diseases such as muscular dystrophy in which both copies of the gene are inactive. People in the study carried only one inactive copy of those genes.
Disease-causing genes tend to have related genes in other species. The disease genes also interact with other genes in a cell more than apparently benign genes do, the researchers found. Learning these rules may aid in predicting how new mutations affect health.