In a twist on "survival of the fittest," researchers including biologist Greg Lang have discovered that evolution is driven not by a single beneficial mutation but rather by a group of mutations, including ones called "genetic hitchhikers" that are simply along for the ride. These hitchhikers are mutations that do not appear to have a role in contributing to an organism's fitness and therefore its evolution, yet may play an important role down the road.

Researchers from Lehigh University, Princeton University, Harvard University, Rowan University, and the Washington University School of Medicine found in a study of 1,000 generations of adaptation in 40 yeast populations that about five to seven specific mutations, rather than just a one, are needed for an organism to succeed. The knowledge of how mutations drive evolution can inform our understanding of how tumors resist chemotherapeutics and how bacteria evolve resistance to antibiotics. The study was published in the journal Nature.

Evolution occurs when an individual experiences spontaneous beneficial mutations in its genome that improve its ability to adapt to its environment. The common view was that a single mutation could boost the survival of an individual, which would then reproduce and pass on the mutation to its offspring.

Instead, the researchers found that rather than just one mutation causing enhanced survival, about five to seven mutations are required. These extra mutations are termed hitchhikers because they don't appear to contribute to the enhanced fitness of the organism.

An evolving population of yeast, starting from a single yeast cell at the far left in which a genetic mutation occurs (red). As the yeast cell reproduces, the mutation is passed on over several generations, as shown by the widening red area. At some point another mutation (orange) occurs in one of the yeast. When the yeast cell reproduces, it passes both the red and orange mutations to its offspring. After a few more generations, another mutation occurs (yellow), bringing the total number of mutations that it carries to three. The study shows that multiple mutations helped the yeast adapt to its environment. In this particular population, another mutation (green) occurred that was far more beneficial for the yeast and the individuals with the orange and yellow mutations were forced to extinction while the cells descended from the yeast with the green mutation took over the population. Image credit: Gregory Lang

"Our study indicates that evolution is more of a group effort," said Lang, the paper’s first author and formely associate research scholar in the Lewis-Sigler Institute for Integrative Genomics at Princeton who will join Lehigh’s biology department this fall. “The traditional view is that adaptation is dominated by rare beneficial mutations that occasionally occur and sweep through a population. In this paper we show this view is, at best, an oversimplification. The most striking feature of our results is that selective sweeps are rarely single mutation/single phase events. Instead, mutations often move through the population in groups, which we have called ‘cohorts.’”

The research team included co-first author Daniel Rice at Harvard University, who made key contributions to the bioinformatics and data analysis; Michael Desai, an assistant professor at Harvard University and a former Lewis-Sigler Fellow at Princeton; Mark Hickman at Rowan University; and Erica Sodergren and George Weinstock at the Washington University School of Medicine.

The study helps expand our understanding of how evolution arises from a combination of genetic mutations, which are thought of as occurring spontaneously, and environmental pressures, said Botstein. "We've shown that this first component, the genetics, involves not just one gene mutation but several that need to co-exist before evolution can happen."

The study was funded with support from a National Science Foundation Graduate Research Fellowship, the National Institute of General Medical Sciences Centers of Excellence grants GM071508 and NIH grant GM046406, the James S. McDonnell Foundation, the Alfred P. Sloan Foundation, and the Harvard Milton Fund.

Thanks to Catherine Zandonella and Princeton University for covering this research story, conducted while Lang was at Princeton University. For the complete study, visit the American Association for the Advancement of Science page.