Non-coding, but fitness implicating?

Widely distributed noncoding purifying selection in the human genome (PNAS):

It is widely assumed that human noncoding sequences comprise a substantial reservoir for functional variants impacting gene regulation and other chromosomal processes. Evolutionarily conserved noncoding sequences (CNSs) in the human genome have attracted considerable attention for their potential to simplify the search for functional elements and phenotypically important human alleles. A major outstanding question is whether functionally significant human noncoding variation is concentrated in CNSs or distributed more broadly across the genome. Here, we combine wholegenome sequence data from four nonhuman species (chimp, dog, mouse, and rat) with recently available comprehensive human polymorphism data to analyze selection at single-nucleotide resolution. We show that a substantial fraction of active purifying selection in human noncoding sequences occurs outside of CNSs and is diffusely distributed across the genome. This finding suggests the existence of a large complement of human noncoding variants that may impact gene expression and phenotypic traits, the majority of which will escape detection with current approaches to genome analysis.

Purifying selection basically works against mutations which result in functional changes which might be deleterious; so it operates as a constraining force upon genetic diversification.

Related: This post from RPM, The Frailty of Nearly Neutral Hypotheses, is highly recommended.

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