Some gene versions stuck around because fertility advantage outweighs heart disease risk
Babies are little heartbreakers — literally. Genetic variants linked to fertility are also linked to coronary artery disease, a new study finds.
It’s not uncommon to find genes that affect more than one trait, but this is the first time scientists have seen a genetic connection between reproduction and heart disease, the researchers report online June 22 in PLOS Genetics. “Evolution is on a buy now, pay later plan,” says coauthor Stephen Stearns, an evolutionary biologist at Yale University. The connection “leads to a view of us as a bundle of trade-offs,” he says. And in this case, genes’ reproductive benefits apparently outweigh even lethal side effects later in life.
Coronary artery disease — one of the most deadly diseases worldwide — results from plaque accumulation in the arteries that supply blood to the heart. That type of buildup, which can start in young adulthood, has afflicted humans for millennia, and scientists have wondered why the genetic variants complicit in the disease haven’t yet been weeded out of the gene pool.
“There must be some advantage to these genes that makes them worth keeping,” says Shari Grossman, a geneticist at the Broad Institute in Cambridge, Mass., who was not involved in the study.
Researchers examined genetic variants associated with coronary artery disease and found evidence that they spread rapidly through the human population within the last 10,000 years or so. This implies that sometime in relatively recent human history these tweaked genes provided an evolutionary advantage.
Then the researchers reviewed 143 previous studies and discovered many of these same genes were linked to — and probably enhanced — important reproductive functions, such as male and female fertility as well as fetal development and survival. This suggests that the genetic quirks associated with coronary artery disease persisted because the people who had them bore more children.
Having birthrate-boosting genes was probably particularly advantageous in the last several thousand years because of the transition to agriculture, Stearns says. Agriculture led to people settling down and eventually moving to cities, where rampant infectious diseases hiked mortality rates, especially among children. People with these genetic variants would have been more likely to continue their lineage, even if they were predisposed to suffer heart problems later on.
This study may be a warning for gene therapy, since it suggests there are many genetic connections between different bodily functions that scientists don’t yet understand, Stearns says. If doctors want to treat coronary artery disease by editing a person’s DNA, it’s important to know what other traits might be affected.
The new findings also raise questions about the various functions of other disease-related genes, says Hamdi Mbarek, a molecular geneticist at Vrije University Amsterdam who was not involved in the work. For instance, a future study could examine whether genes associated with cancer have any hidden evolutionary benefits.
S.G. Byars et al. Genetic loci associated with coronary artery disease harbor evidence of selection and antagonistic pleiotropy. PLOS Genetics. Published online June 22, 2017. doi: 10.1371/journal.pgen.1006328.
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