Many people think evolution requires thousands or millions of years, but biologists know it can happen fast. Now, thanks to the genomic revolution, researchers can actually track the population-level genetic shifts that mark evolution in action—and they’re doing this in humans. Two studies presented at the Biology of Genomes meeting here last week show how our genomes have changed over centuries or decades, charting how since Roman times the British have evolved to be taller and fairer, and how just in the last generation the effect of a gene that favors cigarette smoking has dwindled in some groups.
“Being able to look at selection in action is exciting,” says Molly Przeworski, an evolutionary biologist at Columbia University. The studies show how the human genome quickly responds to new conditions in subtle but meaningful ways, she says. “It’s a game-changer in terms of understanding evolution.”
Evolutionary biologists have long concentrated on the role of new mutations in generating new traits. But once a new mutation has arisen, it must spread through a population. Every person carries two copies of each gene, but the copies can vary slightly within and between individuals. Mutations in one copy might increase height; those in another copy, or allele, might decrease it. If changing conditions favor, say, tallness, then tall people will have more offspring, and more copies of variants that code for tallness will circulate in the population.
With the help of giant genomic data sets, scientists can now track these evolutionary shifts in allele frequencies over short timescales. Jonathan Pritchard of Stanford University in Palo Alto, California, and his postdoc Yair Field did so by counting unique single-base changes, which are found in every genome. Such rare individual changes, or singletons, are likely recent, because they haven’t had time to spread through the population. Because alleles carry neighboring DNA with them as they circulate, the number of singletons on nearby DNA can be used as a rough molecular clock, indicating how quickly that allele has changed in frequency.
Pritchard’s team analyzed 3000 genomes collected as part of the UK10K sequencing project in the United Kingdom. For each allele of interest in each genome, Field calculated a “singleton density score” based on the density of nearby single, unique mutations. The more intense the selection on an allele, the faster it spreads, and the less time there is for singletons to accumulate near it. The approach can reveal selection over the past 100 generations, or about 2000 years.
Stanford graduate students Natalie Telis and Evan Boyle and postdoc Ziyue Gao found relatively few singletons near alleles that confer lactose tolerance—a trait that enables adults to digest milk—and that code for particular immune system receptors. Among the British, these alleles have evidently been highly selected and have spread rapidly. The team also found fewer singletons near alleles for blond hair and blue eyes, indicating that these traits, too, have rapidly spread over the past 2000 years, Field reported in his talk and on 7 May in the preprint server bioRxiv.org. One evolutionary driver may have been Britain’s gloomy skies: Genes for fair hair also cause lighter skin color, which allows the body to make more vitamin D in conditions of scarce sunlight. Or sexual selection could have been at work, driven by a preference for blond mates.
Other researchers praise the new technique. “This approach seems to allow much more subtle and much more common signals of selection to be detected,” says evolutionary geneticist Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany.
In a sign of the method’s power, Pritchard’s team also detected selection in traits controlled not by a single gene, but by tiny changes in hundreds of genes. Among them are height, head circumference in infants, and hip size in females—crucial for giving birth to those infants. By looking at the density of singletons flanking more than 4 million DNA differences, Pritchard’s team discovered that selection for all three traits occurred across the genome in recent millennia.
Joseph Pickrell, an evolutionary geneticist at New York Genome Center in New York City, has used a different strategy to put selection under an even keener microscope, detecting signs of evolution on the scale of a human lifetime. He and Przeworski took a close look at the genomes of 60,000 people of European ancestry who had been genotyped by Kaiser Permanente in Northern California, and 150,000 people from a massive U.K. sequencing effort called the UK Biobank. They wanted to know whether genetic variants change frequency across individuals of different ages, revealing selection at work within a generation or two. The biobank included relatively few old people, but it did have information about participants’ parents, so the team also looked for connections between parental death and allele frequencies in their children.
In the parents’ generation, for example, the researchers saw a correlation between early death in men and the presence in their children (and therefore presumably in the parents) of a nicotine receptor allele that makes it harder to quit smoking. Many of the men who died young had reached adulthood in the United Kingdom in the 1950s, a time when many British men had a pack-a-day habit. In contrast, the allele’s frequency in women and in people from Northern California did not vary with age, presumably because fewer in these groups smoked heavily and the allele did not affect their survival. As smoking habits have changed, the pressure to weed out the allele has ceased, and its frequency is unchanged in younger men, Pickrell explains. “My guess is we are going to discover a lot of these gene-by-environment effects,” Przeworski says.
Indeed, Pickrell’s team detected other shifts. A set of gene variants associated with late-onset menstruation was more common in longer-lived women, suggesting it might help delay death. Pickrell also reported that the frequency of the ApoE4 allele, which is associated with Alzheimer’s disease, drops in older people because carriers died early. “We can detect selection on the shortest timeframe possible, an individual’s life span,” he says.
Signs of selection on short timescales will always be prey to statistical fluctuations. But together the two projects “point to the power of large studies to understand what factors determine survival and reproduction in humans in present-day societies,” Pääbo says.