Natural selection drivers for diseases and traits

Certain complex human traits and diseases seem to be driven by natural selection, a finding which helps to explain variation in human populations, new research suggests.

Population genetics has revealed that there are substantial differences among worldwide human populations regarding certain phenotypic traits – that is, physical characteristics.

Height, body-mass index (or BMI, a calculation purporting to identify individuals on a scale from underweight to obese), and cardiovascular disease are examples of such variable traits. People in northern latitudes have a mean height greater than other human populations, for instance, while in the UK, people of Afro-Caribbean descent have a lower incidence of heart disease than those of European descent.

A team led by Jian Yang from the University of Queensland’s Institute for Molecular Bioscience and the Queensland Brain Institute, and 2017 winner of the Australian Prime Minister’s Prize for Science, has now attempted to uncover the cause of this intergroup variation. Its findings in the journal Nature Communications point to a larger than expected role for natural selection.

Tracking down the cause of biological traits is tricky, because they can result from various causal mechanisms, including environment, selection, mutation or genetic drift. 

“Environmental factors currently play a role,” says Yang, “but most complex traits have a genetic component. The question is whether or not these differences are the consequence of natural selection or simply the result of what we call ‘genetic drift’ – where gene mutations become more or less frequent in a population by chance.”

Yang and his team sought their answer through single nucleotide polymorphisms (SNPs) – variations in the bonds between the four letters of the genetic alphabet at a specific position in a gene – that can give rise to changes in the phenotype and are often responsible for genetic diseases such as cystic fibrosis.

The team developed a complex statistical simulation tool for comparing a group of well understood control SNPs to those associated with height, weight and schizophrenia.

The tool, using data from the enormous US genomic research project called the Genetic Epidemiology Research on Adult Health and Ageing (GERA) Study, revealed that SNPs for these traits were much more differentiated than the controls, a result consistent with the hypothesis that this variation is driven by natural selection.

However, to truly confirm selection as the cause of a trait, one needs to also establish, beyond the physical trait and its genetic basis, the way the trait affects an organism’s fitness, and the factor in the environment driving the selection. 

While fascinating, Yang’s findings tell only half the story, remaining mostly quiet regarding fitness and environmental selection pressures.

Nonetheless, as the authors write: “These findings expand our understanding of the role of natural selection in shaping the genetic architecture of complex traits in human populations.”

Their research also adds another valuable tool to the repertoire of population genetics for understanding the role of natural selection in shaping human biology.