Genetic variants linked to Alzheimer’s disease and heavy smoking are less frequent in people with longer lifespans, suggesting that natural selection is weeding out these unfavorable variants in some populations, according to an analysis of the genomes of 210,000 people in the U.S. and UK.
New favorable traits evolve when genetic mutations arise that offer a survival edge. As the survivors of each generation pass on those beneficial mutations, the mutations and their adaptive traits become more common in the general population.
Though it may take millions of years for complex traits to evolve, say allowing humans to walk on two legs, evolution itself happens with each generation as adaptive mutations become more frequent in the population.
The genomic revolution has allowed biologists to see the natural selection process in action by making the genetic blueprint of hundreds of thousands of people available for comparison.
By tracking the relative rise and fall of specific mutations across generations of people, scientists can infer which traits are spreading or dwindling.
In a large-scale study, Columbia University researcher Hakhamenesh Mostafavi and colleagues analyzed the genomes of 60,000 people of European ancestry (GERA cohort) genotyped by Kaiser Permanente in California, and 150,000 people in Britain genotyped through the U.K. Biobank.
“Our global understanding of adaptation in humans is limited to indirect statistical inferences from patterns of genetic variation, which are sensitive to past selection pressures,” the authors explained.
“We introduced a method that allowed us to directly observe ongoing selection in humans by identifying genetic variants that affect survival to a given age.”
“We applied our approach to the GERA cohort and parents of the U.K. Biobank participants.”
Two population-level mutation shifts stood out. In women over 70, the researchers saw a drop in the frequency of the ApoE4 gene linked to Alzheimer’s, consistent with earlier research showing that women with one or two copies of the gene tend to die well before those without it.
They saw a similar drop, starting in middle age, in the frequency of a mutation in the CHRNA3 gene associated with heavy smoking in men.
They were surprised to find just two common mutations across the entire human genome that heavily influence survival.
The high power of the analysis should have detected other variants had they existed. This suggests that selection has purged similar variants from the population, even those that act later in life like the ApoE4 and CHRNA3 genes.
“It may be that men who don’t carry these harmful mutations can have more children, or that men and women who live longer can help with their grandchildren, improving their chance of survival,” said co-author Dr. Molly Przeworski, an evolutionary biologist at Columbia University.
“Most traits are determined by dozens to hundreds of mutations, and even in a large sample like this one, their effect on survival can be hard to see.”
To get around this, the team examined sets of mutations associated with 42 common traits, from height to body mass index (BMI), and for each individual in the study, determined what value of the trait they would predict based on their genetics, and whether it influenced survival.
The scientists found that a predisposition for high cholesterol and LDL (bad) cholesterol, high BMI, and heart disease was linked to shorter life spans. To a lesser extent, a predisposition for asthma was also linked to earlier death.
They also found that those genetically predisposed to delayed puberty and child-bearing lived longer — a one-year puberty delay lowered the death rate by 3 to 4% in both men and women; a one-year childbearing delay lowered the death rate by 6% in women.
The researchers take the results as evidence that genetic variants that influence fertility are evolving in some U.S. and Britain populations. But they caution that environment plays a role, too, so that traits that are desirable now may not be in other populations or in the future.
“The environment is constantly changing. A trait associated with a longer lifespan in one population today may no longer be helpful several generations from now or even in other modern day populations,” Mostafavi said.
The results are published in the journal PLoS Biology.
Source: Sci News