The findings are reported by Matthew Rockman, Dagan Loisel, and Greg Wray at Duke University, Matthew Hahn at UC Davis, and David Goldstein and Nicole Soranzo at University College London. By analyzing DNA sequences from humans and other primates and comparing sequences among and within human populations, the researchers have cast light on the evolutionary history of a single DNA base pair that has been shown to influence heart disease.

The genetic trait under study concerns a particular base pair of DNA – one of billions in the human genome – that helps regulate the gene stromelysin-1, or MMP-3. The identity of the DNA base at this position differs between individuals and influences the rate of production of the gene's product, an enzyme that degrades the extracellular matrix that makes up the walls of arteries.

Individuals with the low-expression version of the gene are slightly more prone to atherosclerosis, the narrowing of the arteries associated with the accumulation of plaque in the arterial walls. The new research shows that the high-expression variant increased rapidly in frequency in the ancient European population, though not elsewhere. The rapid increase, which is estimated to have begun around 24,000 years ago, is attributable to the action of natural selection favoring the variant, according to statistical analyses of genetic variation in several human populations.

The researchers' new work also showed that the mutation that created the variant occurred at a site unusually prone to genetic change. By comparing human DNA with that of a diverse range of other primates, they showed that the variation in heart disease susceptibility is partly attributable to a so-called mutational "hotspot" that has naturally occurred in MMP-3's regulatory DNA for millions of years. The researchers estimate that the incidence of heart disease events among modern European males would have been more than 40% higher than it is had there not been selection for the high-expression variant. The cause of the selection in recent evolution remains a subject for speculation; given its usual occurrence late in life, heart disease itself is considered to have been an unlikely driving force.

Matthew V. Rockman, Matthew W. Hahn, Nicole Soranzo, Dagan A. Loisel, David B. Goldstein, and Gregory A. Wray: "Positive Selection on MMP3 Regulation Has Shaped Heart Disease Risk"