Pseudogenes

PseudogenesYusufTutar1,2,31DepartmentofBiochemistry,FacultyofMedicine,CumhuriyetUniversity,58140Sivas,Turkey2DepartmentofChemistry,FacultyofScience,CumhuriyetUniversity,58140Sivas,Turkey3CUTFAMResearchCenter,FacultyofMedicine,CumhuriyetUniversity,58140Sivas,TurkeyReceived29August2011;Accepted6February2012AcademicEditor:H.HengCopyright©2012YusufTutar.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense,whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited.AbstractPseudogenesareubiquitousandabundantingenomes.Pseudogeneswereoncecalled“genomicfossils”andtreatedas“junkDNA”severalyears.Nevertheless,ithasbeenrecognizedthatsomepseudogenesplayessentialrolesingeneregulationoftheirparentgenes,andmanypseudogenesaretranscribedintoRNA.PseudogenetranscriptsmayalsoformsmallinterferingRNAordecreasecellularmiRNAconcentration.Thus,pseudogenesregulatetumorsuppressorsandoncogenes.Theiressentialfunctionsdrawtheattentionofourresearchgroupinmycurrentworkonheatshockprotein90:achaperoneofoncogenes.Thepaperreviewsourcurrentknowledgeonpseudogenesandevaluatespreliminaryresultsofthechaperonedata.Currenteffortstounderstandpseudogenesinteractionshelptounderstandthefunctionsofagenome.1.HistoryofPseudogenesSequencinghumangenomebroughtseveraldebatesaboutnoncodingsequences.Sowhatistheroleofthenoncodingpartssinceproteincodingexonscompromiseonlyaroundtwopercentofthewholegenomesequence?Thenoncodingregionsaretransposableelements,structuralvariants,segmentalduplications,simpleandtandemrepeats,conservednoncodingelements,functionalnoncodingRNAs,regulatoryelements,andpseudogenes[1].Annotationofthesenoncodingregionsthroughfunctionalgenomicsandsequenceanalysishelpsourunderstandingofgenomics.Noncodingregionsofhumangenomeingeneralwerethoughttobenonfunctionaland“junk,”orofnopurposeDNA.Nowadays,scientistsareconcedingthatjunkDNAterminologyisfarfromtruesincerecentstudiesindicatethattheyhavesomeregulatoryroles.ThisworkfocusesonpseudogenesofjunkDNA.Pseudogenesaregenecopiesthathavecoding-sequencedeficiencieslikeframeshiftsandprematurestopcodonsbutresemblefunctionalgenes.Thefirstpseudogenewasreportedfor5SDNAofXenopuslaevis,codingforoocyte-type5SRNA,in1977,andseveralpseudogeneshavebeenreportedanddescribedforavarietyofspeciesincludingplants,insects,andbacteria[2,3].Currently,approximatelytwentythousandpseudogenesareestimatedwhichiscomparabletothenumberofprotein-codinggenes(around27000)inhuman[4].Currentknowledgeofthesegenesremainspoorlyunderstood,andmanysequencesoncebelieveddefunctareinfactfunctionalRNAgenesandplayrolesingenesilencingeitherbyformingsiRNAsorbychangingmRNAlevelsoffunctionalprotein-codinggene[5].Severalstudiesfocusedonthepseudogenepopulationandtheirregulatoryrolesasthefunctionofmorepseudogenesisbeinguncovered.Itisinterestingtocompareandcontrastgenesfromavarietyoforganismstodeterminetheiradaptationforsurvival.Pseudogenesprovidearecordofallchangesinthegenomeofaparticularorganism.2.TypesofPseudogenesPseudogenescanbecategorizedintwoforms:unprocessedandprocessed.Unprocessedpseudogenescanalsobesubcategorizedasunitaryandduplicated[3,6].Pseudogenesoriginatefromdecayofgenesthatoriginatedfromduplicationthroughevolution.Thedecaysincludepointmutations,insertions,deletions,misplacedstopcodons,orframeshiftsofagene.Thedecaymayoccurduringduplication,andthesedisablementsmaycauselossofagenefunction.Lossofproductivity,expressionofRNAorproteincodingability,resultsintheproductionofunprocessedpseudogenes.AuniquesubfamilyofunprocessedpseudogenesaredescribedbyZhangetal.Formationofnonduplicatedunprocessedpseudogenesisnamed“unitary”pseudogenes[7].Inunitarytypeofpseudogenes,asinglecopyparentgenebecomesnonfunctional.Unprocessedandduplicatedpseudogeneskeeptheirintron-exonstructure.Processedpseudogenesareformedthroughretrotransposition.RetrotranspositionoccursbyreintegrationofacDNA,areversetranscribedmRNAtranscript,intothegenomeatanewlocation.Thedouble-strandedsequencesofprocessedpseudogenesaregeneratedfromsingle-strandRNAbyRNApolymeraseIIratherthantheRNApolymeraseIII.Therefore,processedpseudogeneslackintrons,5′promotersequence,andhaveflankingdirectrepeatsand3′polyadenylationtag.Theoveralldistributionofmostpseudogenesiscompletelyrandom,duplicated,andprocessedpseudogenesarefoundinthesameorondifferentchromosomeoftheirparentgenes.DuplicationofDNAsegmentsexplainsthegenerationofgenefamiliesfromacommonancestralgene.Thedynamicnatureofgenomecausechangesinitscompositionwithtime.3.WhyDoOrganismsKeepPseudogenes?Whyorganismsmaintainpseudogenesandpayacostofenergy?Replicationofthesegenesovergenerationsisadisadvantageousbiochemicalprocess.WhywouldnotnaturalselectionremovethesecostlyDNAsegments?Whatisthepotentialbenefittokeepnon-protein-codingsequences?Whyarehighlyexpressedgenesmorelikelytoproducepseudogenes?Dothepseudogenesaccumulateallkindsofmutationincludingdeleteriousonestoprotectthefunctionalgenes?Geneduplicationsmakefunctionaldivergenceandgeneratenewgenes[8].Unprocessedpseudogeneshaveintronsandregulatorysequences