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Is there a twelfth protein-coding gene in the genome of influenza A? A selection-based approach to the detection of overlapping genes in closely related sequences


Sabath, Niv; Morris, Jeffrey S; Graur, Dan (2011). Is there a twelfth protein-coding gene in the genome of influenza A? A selection-based approach to the detection of overlapping genes in closely related sequences. Journal of Molecular Evolution, 73(5-6):305-315.

Abstract

Protein-coding genes often contain long overlapping open-reading frames (ORFs), which may or may not be functional. Current methods that utilize the signature of purifying selection to detect functional overlapping genes are limited to the analysis of sequences from divergent species, thus rendering them inapplicable to genes found only in closely related sequences. Here, we present a method for the detection of selection signatures on overlapping reading frames by using closely related sequences, and apply the method to several known overlapping genes, and to an overlapping ORF on the negative strand of segment 8 of influenza A virus (NEG8), for which the suggestion has been made that it is functional. We find no evidence that NEG8 is under selection, suggesting that the intact reading frame might be non-functional, although we cannot fully exclude the possibility that the method is not sensitive enough to detect the signature of selection acting on this gene. We present the limitations of the method using known overlapping genes and suggest several approaches to improve it in future studies. Finally, we examine alternative explanations for the sequence conservation of NEG8 in the absence of selection. We show that overlap type and genomic context affect the conservation of intact overlapping ORFs and should therefore be considered in any attempt of estimating the signature of selection in overlapping genes

Abstract

Protein-coding genes often contain long overlapping open-reading frames (ORFs), which may or may not be functional. Current methods that utilize the signature of purifying selection to detect functional overlapping genes are limited to the analysis of sequences from divergent species, thus rendering them inapplicable to genes found only in closely related sequences. Here, we present a method for the detection of selection signatures on overlapping reading frames by using closely related sequences, and apply the method to several known overlapping genes, and to an overlapping ORF on the negative strand of segment 8 of influenza A virus (NEG8), for which the suggestion has been made that it is functional. We find no evidence that NEG8 is under selection, suggesting that the intact reading frame might be non-functional, although we cannot fully exclude the possibility that the method is not sensitive enough to detect the signature of selection acting on this gene. We present the limitations of the method using known overlapping genes and suggest several approaches to improve it in future studies. Finally, we examine alternative explanations for the sequence conservation of NEG8 in the absence of selection. We show that overlap type and genomic context affect the conservation of intact overlapping ORFs and should therefore be considered in any attempt of estimating the signature of selection in overlapping genes

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Item Type:Journal Article, refereed, original work
Communities & Collections:National licences > 142-005
Dewey Decimal Classification:570 Life sciences; biology
590 Animals (Zoology)
Scopus Subject Areas:Life Sciences > Ecology, Evolution, Behavior and Systematics
Life Sciences > Molecular Biology
Life Sciences > Genetics
Language:English
Date:1 December 2011
Deposited On:13 Dec 2018 16:16
Last Modified:15 Apr 2021 14:53
Publisher:Springer
ISSN:0022-2844
OA Status:Green
Publisher DOI:https://doi.org/10.1007/s00239-011-9477-9
PubMed ID:22187135

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