‘Selfish’ DNA flouts rules of inheritance

In the Star Wars movies, the droid R2D2 is a heroic rebel. In living animals, a selfish bit of DNA called R2d2 is an outright lawbreaker. It violates laws of both genetic inheritance and Darwinian evolution. R2d2 can sweep through mouse populations by mimicking helpful mutations while actually damaging fertility, researchers report online February 15 in Molecular Biology and Evolution.

The new findings suggest that even genes that hurt an organism’s evolutionary chances can cheat their way to the top. That could be good news for researchers hoping to use engineered “gene drives” to eliminate mosquito-borne diseases and invasive species. But it’s also a cautionary tale for scientists looking for signs that natural selection has picked certain genes because they offer an evolutionary benefit.

If researchers aren’t careful, they may be hoodwinked into thinking that a selfish gene is one that has some evolutionary advantage, says Daven Presgraves, an evolutionary geneticist at the University of Rochester in New York. The genetic signatures are the same, he says. But what looks like survival of the fittest may actually be a cheater prospering.

Geneticist John Didion and colleagues examined DNA samples from wild mice from Europe, the United States and elsewhere to determine how widespread R2d2 has become. The researchers also bred strains of mice in the lab to determine how quickly R2d2 is capable of spreading. The selfish DNA could blaze through populations, reports Didion, formerly of the University of North Carolina at Chapel Hill. The proportion of mouse chromosomes with the selfish gene — called the allele frequency — more than tripled in one laboratory population from 18 percent to 62 percent within 13 generations, the researchers found.

In another breeding population, R2d2 shot from being in 50 percent of the lab mice’s chromosomes to 85 percent in 10 generations. By 15 generations, the selfish element reached “fixation” — all the mice in the population carried it. That rate of spread was much faster than Didion, now at the National Human Genome Research Institute in Bethesda, Md., and colleagues predicted. Computer simulations had projected it would take 184 generations for the selfish DNA to spread to all of the mice. 

Such wildfire spread of a gene variant that eventually wipes out all other versions is known as a selective sweep. Sweeps are hallmarks of a gene that helps an organism adapt to its environment. But this study suggests that what looks like adaptation may actually be selfish genetics at work, says Nitin Phadnis, an evolutionary geneticist at the University of Utah in Salt Lake City.

R2d2 is a “selfish element,” a gene or other piece of DNA that causes itself to be inherited preferentially, researchers at UNC Chapel Hill reported last year. The droid’s namesake is a stretch of DNA on mouse chromosome 2 that contains multiple copies of the Cwc22 gene. When seven or more copies of that gene build up on the chromosome, R2d2 gets selfish. In female mice, it elbows aside the chromosome that doesn’t contain the selfish version of the gene and is preferentially incorporated into eggs. That’s a violation of the laws of inheritance spelled out by Gregor Mendel in which each gene or chromosome is supposed to have a fifty-fifty chance of being passed on to the next generation. But there is a cost to R2d2’s selfishness: Female mice that carry one copy of the selfish element have small litter sizes compared with mice that don’t carry the greedy DNA.

Under evolutionary laws, that loss of fertility should cause natural selection to weed out R2d2. But the selfish element’s greed is greater than the power of natural selection to combat it, the lab experiments show.

Even the most successful cheat can get caught, though. Wild mice in Europe and at two sites in the United States had widely varying proportions of the selfish gene, Didion and colleagues found. In a population of German mice, R2d2’s frequency was 67 percent, but only 8 percent in Greek mice. In Maryland, where mice carrying R2d2 were first found, 21 percent of  chromosomes carried it. The selfish element may not have crossed the country yet. None of the mice the researchers tested from California had R2d2.

Based on lab experiments, the researchers might have expected all the wild mice they tested to carry the deceptive DNA. The relatively low proportion of wild mice carrying R2d2 could mean that some mice have developed ways to suppress the gene’s selfishness, says Matthew Dean, an evolutionary geneticist at the University of Southern California in Los Angeles.

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Editor’s note: This story was updated March 4, 2016, to correct the measure researchers used to determine the spread of R2d2.