Understanding the rules of life

Category: Standard Studentships

How much of the human genome is functional?

Project No.2215

Primary Supervisor

Prof Adam Eyre-Walker – University of Sussex


Dr. Marta Farré Belmonte – University of Kent



How much of the human genome is functional?

This is a question that continues to generate considerable debate – whilst 80% of the human genome is biochemically active, in the sense that it is transcribed or binds a protein, only 5-10% of the genome seems to be constrained by natural selection. Understanding how much and which parts of the genome are critical for function, is fundamental to understanding the genome and predicting which mutations might be harmful, a major

goal of human disease genetics. However, a major challenge in determining which sequences are important is turnover, the tendency for the sequences that are functional to evolve and move; this makes detecting these sequences challenging, because a sequence that is important to function in humans may not be important to other species and hence not conserved. The aim of the studentship proposal is to initiate a series of innovative studies that will help determine the functional component of the human genome and to investigate whether we can predict which sites are important. We will develop novel models of turnover that allow sites and sequences to evolve at different rates. We will fit these models to data to infer the fraction of the genome that is subject to selection. These inferences will be made for different classes of sites – e.g. DNA hypersensitivity sites – allowing us to infer which categories of sites are most likely to be functional, and the rate at which they turnover. We will also take a parallel path, using population genetic data to infer the fitness effects of new mutations at different sites in the genome. Together these strands will bring new insights into the functional component of the human genome and disease genetics.