GC Content Increased at CpG Flanking Positions of Fish Genes Compared with Sea Squirt Orthologs as a Mechanism for Reducing Impact of DNA Methylation 英文参考文献.docVIP

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GC Content Increased at CpG Flanking Positions of Fish Genes Compared with Sea Squirt Orthologs as a Mechanism for Reducing Impact of DNA Methylation 英文参考文献.doc

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GC Content Increased at CpG Flanking Positions of Fish Genes Compared with Sea Squirt Orthologs as a Mechanism for Reducing Impact of DNA Methylation 英文参考文献

GCContentIncreasedatCpGFlankingPositionsofFish GenesComparedwithSeaSquirtOrthologsasa MechanismforReducingImpactofDNAMethylation YongWang*,FrederickC.C.Leung DepartmentofZoologyandGenomeResearchCentre,TheUniversityofHongKong,Pokfulam,HongKong Abstract Background: FractionalDNAmethylationin seasquirtsevolvedtoglobalDNAmethylation infish.Theimpact ofglobal DNAmethylationisreflectedbymoreCpGdepletionsand/ormoreA/TtoG/CchangesatCpGflankingpositionsdueto context-dependentmutationsofmethylatedCpGsites. MethodsandFindings:Inthisreport,wedemonstratethattheseasquirtgeneshaveundergonemoreCpGtoTpG/CpA substitutionsthanthefishorthologsusinghomologousfragmentsfromorthologousgenesamongCionaintestinalis,Ciona savignyi,fugufishandzebrafish.Toavoidprematuretranscription,theTGAsitesderivedfromCGAwerelargelyconvertedto TGG in sea squirt genes. By contrast, a significant increment of GC content at CpG flanking positions wasshown in fish genes. The positively selected A/T to G/C substitutions, in combination with the CpG to TpG/CpA substitutions, are the sourcesoftheextremelylowCpGobserved/expectedratiosinvertebrates.Thenonsynonymoussubstitutionscausedby the GC content increase have resulted in frequent amino acid replacements in the directions that were not noticed previously. Conclusion:TheincreasedGCcontentatCpGflankingpositionscanreduceCpGlossinfishgenesandattenuatetheimpact ofDNAmethylationonCpG-containingcodons,probablyaccountingforevolutiontowardsvertebrates. Citation:WangY,LeungFCC(2008)GCContentIncreasedatCpGFlankingPositionsofFishGenesComparedwithSeaSquirtOrthologsasaMechanismfor ReducingImpactofDNAMethylation.PLoSONE3(11):e3612.doi:10.1371/journal.pone.0003612 Editor:Jean-NicolasVolff,EcoleNormaleSupe′rieure deLyon,France ReceivedSeptember11,2008;AcceptedOctober13,2008;PublishedNovember13,2008 Copyright: ? 2008 Wang, Leung. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distributio