Comparative Genomic Study Reveals a Transition from TA Richness in Invertebrates to GC Richness in Vertebrates at CpG Flanking Sites： An Indication for Context-Dependent Mutagenicity of Methylated CpG Sites

VertebrategenomesarecharacterizedwithCpGdeficiency,particularlyforGC-poorregions.TheGCcontent-relatedCpGdeficiencyisprobablycausedbycontext-dependentdeaminationofmethylatedCpGsites.ThishypothesiswasexaminedinthisstudybycomparingnucleotidefrequenciesatCpGflankingpo-sitionsamonginvertebrateandvertebrategenomes.Thefindingisatransitionofnucleotidepreferenceof5'Tto5'Aattheinvertebrate-vertebrateboundary,indi-catingthatalargenumberofCpGsiteswith5TsweredepletedbecauseofglobalDNAmethylationdevelopedinvertebrates.Atgenomelevel,weinvestigatedCpGobserved/expected(obs/exp)valuesin500bpfragments,andfoundthathigherCpGobs/expvalueisshowninGC-poorregionsofinvertebrategenomes(exceptseaurchin)butinGC-richsequencesofvertebrategenomes.WenextcomparedGCcontentatCpGflankingpositionswithgenomicaverage,showingthattheGCcontentislowerthantheaverageininvertebrategenomes,buthigherthanthatinvertebrategenomes.Theseresultsindicatethatalthough5'Tand5'AaredifferentininducingdeaminationofmethylatedCpGsites,GCcontentisevenmoreimportantinaffectingthedeaminationrate.Inallthetests,theresultsofseaurchinaresimilartovertebratesperhapsduetoitsfractionalDNAmethylation.CpGdeficiencyisthereforesuggestedtobemainlyaresultofhighmutationratesofmethylatedCpGsitesinGC-poorregions.