The role of epigenetics in evolution

Every young biologist learns about DNA, the genetic code and how mutations in that code lead to variation. However, it is less well known that a gene's activity or function can be modified without any change in the genetic sequence; this type of modification is known as epigenetics. Epigenetics has become an important and timely topic across most fields of biological research including medicine, animal and plant breeding, developmental biology and the discipline I work in, evolutionary genetics.

The commonest form of epigenetic effect is known as methylation, which most frequently arises when a methyl group (-CH3) replaces a hydrogen ion on the pyrimidine ring of the nucleotide cytosine (the DNA 'letter' C). Methylation can happen at C bases all over the genome, and it is thought to have the potential to effect how particular genes are expressed and regulated i.e. it could determine which tissues a gene is 'turned on in' and when it is turned on. It is becoming increasingly apparent that there is a great deal of variation in methlyation e.g. between individuals, between different tissues in the same individual and at different times in an individual's lifetime. However, we know very little about whether this variation in methylation has consequences for how phenotypes are expressed, how it is inherited, and whether it can play an important role in evolutionary change.

This project seeks to understand the role of epigenetics on evolutionary change in two discrete but complementary work packages. The work will be done in a population of Soay sheep on the island of Hirta, St Kilda in the Outer Hebrides. This population is one of the best studied mammal populations in the world. It has many features that make it ideal to explore the role of epigenetics on evolution. Complete life histories are known for around 10,000 sheep born since 1985. Environmental conditions on the island are challenging, meaning natural selection is strong enough for evolutionary change to have been witnessed and measured in the lifetime of the study. Extensive genomics resources are already available, along with freezers full of archived material.

Both work packages will be underpinned by an initial goal of sequencing 1000 entire methylomes (the methylation equivelent of a genome) Work Package 1 will explore whether epigenetic variation explains substantial amounts of phenotypic variation. If it does, is that variation heritable? And if it is heritable, is that variation responsible for the so-called 'missing heritability', where conventional (DNA-sequence based) genome scans fail to identify all of the genetic variants affecting a trait? Work Package 2 will test ideas that methylation is sensitive to environmental conditions and can reveal new insights into previous life experiences, body condition, and future longevity. WP1 will resolve topical and controversial questions about the relative importance of genetics and epigenetics on phenotypic variation and evolutionary change. WP2 will result in the first application of epigenetic clocks to study health and ageing in any wild animal population. Together, the outcomes will give unprecedented insight into the environmental and genetic causes of variation in methylation and what that variation means for individual fitness and a population's ability to respond and adapt to environmental change.