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Genome Biol. 2013 May 27;14(5):R49. doi: 10.1186/gb-2013-14-5-r49.

Mutations within lncRNAs are effectively selected against in fruitfly but not in human.

Abstract

BACKGROUND:

Previous studies in Drosophila and mammals have revealed levels of long non-coding RNAs (lncRNAs) sequence conservation that are intermediate between neutrally evolving and protein-coding sequence. These analyses compared conservation between species that diverged up to 75 million years ago. However, analysis of sequence polymorphisms within a species' population can provide an understanding of essentially contemporaneous selective constraints that are acting on lncRNAs and can quantify the deleterious effect of mutations occurring within these loci.

RESULTS:

We took advantage of polymorphisms derived from the genome sequences of 163 Drosophila melanogaster strains and 174 human individuals to calculate the distribution of fitness effects of single nucleotide polymorphisms occurring within intergenic lncRNAs and compared this to distributions for SNPs present within putatively neutral or protein-coding sequences. Our observations show that in D.melanogaster there is a significant excess of rare frequency variants within intergenic lncRNAs relative to neutrally evolving sequences, whereas selection on human intergenic lncRNAs appears to be effectively neutral. Approximately 30% of mutations within these fruitfly lncRNAs are estimated as being weakly deleterious.

CONCLUSIONS:

These contrasting results can be attributed to the large difference in effective population sizes between the two species. Our results suggest that while the sequences of lncRNAs will be well conserved across insect species, such loci in mammals will accumulate greater proportions of deleterious changes through genetic drift.

PMID:
23710818
[PubMed - in process]
PMCID:
PMC4053968
Free PMC Article

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