The risk of developing multiple sclerosis (MS) is determined by both genetics and the environment. It is more common in people of European ancestry, and more common further from the equator within those populations.
It is likely that this pattern has been shaped by natural selection, or selection in response to environmental factors.
Natural selection is a feature of biology that drives evolutionary change. While individual gene variations are random, pressure from the environment weeds out those that harm survival and boosts those that help an individual stay alive long enough to reproduce. This means that beneficial genes spread through populations at rates higher than you would expect by chance.
Many human genes have undergone recent and historical natural selection to adapt to diets, climates, diseases, and high-altitude environments. Identifying genes that have undergone selection and alter MS risk will improve understanding of what causes the disease.
This project was designed to identify specific combinations of genetic variations that may result in MS onset and have undergone natural selection and help to understand the mechanisms of disease.
This study carried out genome-wide scans; that is, scanning all of the DNA (the genome) across thousands of people to look for small common differences.
The aim was to find evidence for natural selection and targeted regions of the genome known to be associated with MS risk. This will help uncover the selective forces that have driven the differences in MS risk between populations, to better understand the molecular mechanisms behind the disease.
Dr Bennet McComish and his team examined the evolutionary causes of the strong latitude gradient in MS prevalence that is observed in some populations. Identifying specific genes that are under natural selection will help to better target therapies aimed at these risk factors.
The team tested whether specific combinations of genetic variations that have undergone selection are associated with MS, giving us a more detailed picture of the genetic architecture that contributes to risk than we can see by considering changes one by one. Data from various parts of cell biology were investigated to confirm the importance of the genes identified.
Dr McComish and his team have identified genes involved in autoimmune disease that have been subject to natural selection. Some of these are likely to be relevant to MS. The team has started narrowing down the genetic variations that are most likely to have important functional impacts within some of those genes.
The team has identified genes that have undergone recent natural selection driven by solar radiation levels in the UK. Solar radiation levels are strongly linked to latitude (the distance from the equator) and may help to explain why MS is more common further from the equator. There was strong evidence for natural selection of variants in the genes for “toll-like receptors” which are part of the body’s first line of defence against foreign invaders. These genes are also known to be linked to vitamin D. This supports a possible link between these gene variations and MS.
These gene variations may help to identify drug targets for developing treatments. Dr McComish and his team are currently preparing three manuscripts on their study for publication in peer reviewed journals.
Updated 31 March 2026
$124,843
2023
3 years
Past project
