Assessing Recent Selection and Functionality at Long Noncoding RNA Loci in theMouse Genome.

Long noncoding RNAs (lncRNAs) are one of themost intensively studied groups of noncoding elements.Debate continues overwhat proportion of lncRNAs are functional ormerely represent transcriptional noise. Although characterization of individual lncRNAs has identified approximately 200 functional loci across the Eukarya, general surveys have found only modest or no evidence of long-term evolutionary conservation. Although this lack of conservation suggests that most lncRNAs are nonfunctional, the possibility remains thatsomerepresent recent evolutionary innovations.Weexaminerecent selectionpressuresactingonlncRNAsinmousepopulations. Wecomparepatternsof within-species nucleotide variation at approximately10,000 lncRNAloci ina cohort of the wild housemouse, Mus musculus castaneus, with between-species nucleotide divergence from the rat (Rattus norvegicus). Loci under selective constraint are expected to show reduced nucleotide diversity and divergence. We find limited evidence of sequence conservation comparedwithputativelyneutrally evolving ancestral repeats (ARs).Comparisonsof sequence diversity anddivergence betweenARs, protein-coding (PC) exons and lncRNAs, and the associated flanking regions, show weak, but significantly lower levels of sequence diversity and divergence at lncRNAs compared with ARs. lncRNAs conserved deep in the vertebrate phylogeny show lower withinspecies sequence diversity than lncRNAs in general. A set of 74 functionally characterized lncRNAs show levels of diversity and divergence comparable to PC exons, suggesting that these lncRNAs are under substantial selective constraints. Our results suggest that, inmouse populations,most lncRNA loci evolve at rates similar to ARs,whereas older lncRNAs tend to show signals of selection similar to PC genes. [ABSTRACT FROM AUTHOR]