MolEpi meeting: The consequences of pervasive promoter birth and death for human genetic and phenotypic variation

Dr Rob Young  on "The consequences of pervasive promoter birth and death for human genetic and phenotypic variation".

Synopsis of Rob's talk: "Promoters are critically important regulatory loci which contain the site of gene transcription initiation. They also harbour a high concentration of phenotype-associated genetic variants, which can drive high cholesterol as well as diseases such as beta-thalassaemia and Bernard-Soulier syndrome. Evolutionary birth and death (collectively, turnover) of promoters is pervasive across mammalian genomes and may therefore play a prominent role in regulating genetic and phenotypic diversity.

Here, I will discuss how the evolutionary processes which created and destroyed functional promoters are continuing, although these events do not currently appear to be experiencing selective pressures within the human population. Those promoters which have experienced sequence, but not functional, turnover are particularly enriched for regulatory variants at all stages of gene expression and across tissues. Once they arise, these promoters generally accumulate mutations which suppress gene expression. Promoter turnover drives increased variance in gene expression across individuals and tissues but this effect, particularly for promoters whose underlying DNA is conserved, is buffered by functionally conserved promoters. These evolutionarily volatile loci may represent hotspots for deleterious mutations which drive variation in quantitative traits and human disease".