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

Haerty, Wilfried ORCID: https://orcid.org/0000-0003-0111-191X and Ponting, Chris P. (2013) Mutations within lncRNAs are effectively selected against in fruitfly but not in human. Genome Biology, 14 (5). ISSN 1474-760X

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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.

Item Type: Article
Additional Information: Funding Information: We are extremely grateful to Dr. Peter Keightley for making DFE alpha available and for the use of his servers. We are grateful to Andrew Bassett, Ana Marques, Christoffer Nellåker and Chris Rands for their comments on early versions of this manuscript. WH and CPP are supported by the Medical Research Council (MRC). This work was also supported by an ERC Advanced Grant to CPP.
Uncontrolled Keywords: ecology, evolution, behavior and systematics,genetics,cell biology ,/dk/atira/pure/subjectarea/asjc/1100/1105
Faculty \ School: Faculty of Science > School of Biological Sciences
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Depositing User: LivePure Connector
Date Deposited: 15 Sep 2022 14:30
Last Modified: 23 Sep 2022 02:59
URI: https://ueaeprints.uea.ac.uk/id/eprint/88331
DOI: 10.1186/gb-2013-14-5-r49

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