Study: Natural Selection Still at Work in Humans

An international team of scientists from Australia, the Netherlands, Estonia and the United States has detected significant signatures of natural selection in the human genome that influence traits associated with fertility and heart function.

Zeng et al detected signatures of natural selection in the genetic architecture of 23 complex traits.

Zeng et al detected signatures of natural selection in the genetic architecture of 23 complex traits.

The team, led by University of Queensland’s Professor Jian Yang and Dr. Jian Zeng, developed a statistical method to examine the effect of DNA variants on genetic architecture.

“In natural selection, or ‘survival of the fittest’, characteristics that improve survival are more likely to be passed on to the next generation. The opposite also occurs, when DNA mutations with a detrimental effect on fitness are less likely to be passed on, by a process called negative selection,” Professor Yang said.

The researchers applied their method to 28 complex traits in the UK Biobank data (126,545 individuals of European ancestry) and to 27,869 gene expression traits in the Consortium for the Architecture of Gene Expression data.

They found evidence of negative selection on DNA variants associated with 23 traits, including reproductive, cardiovascular, and anthropometric traits, as well as educational attainment.

“Among the strongest associations was with traits related to cardiovascular function, such as waist-to-hip ratio, with excess fat around the waist thought to increase the risk of heart disease and type 2 diabetes,” Professor Yang noted.

“The most significant negative selection of DNA mutations was related to reproductive function, such as age at menopause,” Dr. Zeng added.

“We found genetic variants associated with fertility seem to have undergone the strongest selection compared to those associated with other traits, likely because of the strong correlation between fertility and genetic fitness.”

“Negative selection prevents ‘bad’ mutations from spreading through the population, meaning that common DNA variants are likely to have small or no effect on traits.”

“This study will help us better understand the genetic basis of complex traits and inform the design of future experiments in complex traits and medical genomics.”

The study was published in the journal Nature Genetics.

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Jian Zeng et al. Signatures of negative selection in the genetic architecture of human complex traits. Nature Genetics, published online April 16, 2018; doi: 10.1038/s41588-018-0101-4

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