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dc.contributor.authorMacqueen, Daniel J.
dc.contributor.authorJohnston, Ian A.
dc.date.accessioned2012-11-27T16:01:10Z
dc.date.available2012-11-27T16:01:10Z
dc.date.issued2009-02-06
dc.identifier.citationMacqueen , D J & Johnston , I A 2009 , ' Evolution of the multifaceted eukaryotic akirin gene family ' , BMC Evolutionary Biology , vol. 9 , 34 . https://doi.org/10.1186/1471-2148-9-34en
dc.identifier.issn1471-2148
dc.identifier.otherPURE: 9507276
dc.identifier.otherPURE UUID: 23fa3e04-3975-4718-8de0-0c7fb4307022
dc.identifier.otherWOS: 000264930500002
dc.identifier.otherScopus: 63049096659
dc.identifier.otherORCID: /0000-0002-7796-5754/work/47136010
dc.identifier.urihttps://hdl.handle.net/10023/3275
dc.description.abstractBackground: Akirins are nuclear proteins that form part of an innate immune response pathway conserved in Drosophila and mice. This studies aim was to characterise the evolution of akirin gene structure and protein function in the eukaryotes. Results: akirin genes are present throughout the metazoa and arose before the separation of animal, plant and fungi lineages. Using comprehensive phylogenetic analysis, coupled with comparisons of conserved synteny and genomic organisation, we show that the intron-exon structure of metazoan akirin genes was established prior to the bilateria and that a single proto-orthologue duplicated in the vertebrates, before the gnathostome-agnathan separation, producing akirin1 and akirin2. Phylogenetic analyses of seven vertebrate gene families with members in chromosomal proximity to both akirin1 and akirin2 were compatible with a common duplication event affecting the genomic neighbourhood of the akirin proto-orthologue. A further duplication of akirins occurred in the teleost lineage and was followed by lineage-specific patterns of paralogue loss. Remarkably, akirins have been independently characterised by five research groups under different aliases and a comparison of the available literature revealed diverse functions, generally in regulating gene expression. For example, akirin was characterised in arthropods as subolesin, an important growth factor and in Drosophila as bhringi, which has an essential myogenic role. In vertebrates, akirin1 was named mighty in mice and was shown to regulate myogenesis, whereas akirin2 was characterised as FB11 in rats and promoted carcinogenesis, acting as a transcriptional repressor when bound to a 14-3-3 protein. Both vertebrate Akirins have evolved under comparably strict constraints of purifying selection, although a likelihood ratio test predicted that functional divergence has occurred between paralogues. Bayesian and maximum likelihood tests identified amino-acid positions where the rate of evolution had shifted significantly between paralogues. Interestingly, the highest scoring position was within a conserved, validated binding-site for 14-3-3 proteins. Conclusion: This work offers an evolutionary framework to facilitate future studies of eukaryotic akirins and provides insight into their multifaceted and conserved biochemical functions.
dc.format.extent20
dc.language.isoeng
dc.relation.ispartofBMC Evolutionary Biologyen
dc.rights© 2009 Macqueen and Johnston; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.subjectNF-KAPPA-Ben
dc.subjectGenome duplicationen
dc.subjectDrosophila-melanogasteren
dc.subjectFunctional divergenceen
dc.subjectPhylogenetic analysisen
dc.subjectSequence alignmentsen
dc.subjectMaximum-likelihooden
dc.subjectNuclear exporten
dc.subjectIn-vitroen
dc.subject2 roundsen
dc.subjectQH426 Geneticsen
dc.subject.lccQH426en
dc.titleEvolution of the multifaceted eukaryotic akirin gene familyen
dc.typeJournal articleen
dc.contributor.sponsorNERCen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews. School of Biologyen
dc.contributor.institutionUniversity of St Andrews. Scottish Oceans Instituteen
dc.contributor.institutionUniversity of St Andrews. Centre for Research into Ecological & Environmental Modellingen
dc.contributor.institutionUniversity of St Andrews. Marine Alliance for Science & Technology Scotlanden
dc.identifier.doihttps://doi.org/10.1186/1471-2148-9-34
dc.description.statusPeer revieweden
dc.identifier.grantnumberNE/E015212/1en


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