Abstract
the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly
growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While
the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong
indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several
classes of regulatory elements.
Results: We disentangle signals of purifying selection acting directly on regulatory elements from the confounding
factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance
of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We
note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes
were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection
efficacy across genomic classes differed between African and non-African populations.
Conclusions: In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is
crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study
highlights the intricate interplay of factors affecting signals of selection on functional elements.