The Interrupted Gene
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© Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC 14 NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION A self-splicing© Jones intron in & an Bartlett rRNA of the Learning, large ribosomal LLC subunit. © Kenneth Eward/Photo© Researchers, Jones &Inc. Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION The Interrupted Gene Edited by Donald Forsdyke www © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALECHAPTER CHAPTEROR DISTRIBUTION OUTLINE OUTLINE NOT FOR SALE OR DISTRIBUTION 4.1 Introduction • The positions of introns are usually conserved when homologous genes are compared between different or- 4.2 An Interrupted Gene Consists of Exons and Introns ganisms. The lengths of the corresponding introns may • Introns are removed by RNA splicing, which occurs in vary greatly, though. © Jones & Bartlettcis inLearning, individual RNA LLC molecules. © Jones & Bartlett• Introns Learning, usually do not encodeLLC proteins. NOT FOR SALE• ORMutations DISTRIBUTION in exons can affect polypeptide sequence; NOT FOR4.5 SALE Exon ORSequences DISTRIBUTION Under Negative Selection mutations in introns can affect RNA processing and hence may influence the sequence and/or production Are Conserved but Introns Vary of a polypeptide. • Comparisons of related genes in different species show 4.3 that the sequences of the corresponding exons are Exon and Intron Base Compositions Differ usually conserved but the sequences of the introns are • The four “rules”© forJones DNA base & compositionBartlett areLearning, the first LLC much less similar.© Jones & Bartlett Learning, LLC and second parityNOT rules, FOR the clusterSALE rule, OR and DISTRIBUTIONthe GC • Introns evolve muchNOT more FOR rapidly SALE than exons OR DISTRIBUTION rule. Exons and introns can be distinguished on the because of the lack of selective pressure to produce a basis of all rules except the first. polypeptide with a useful sequence. • The second parity rule suggests an extrusion of struc- 4.6 tured stem-loop segments from duplex DNA, which Exon Sequences Under Positive Selection Vary would be greater in introns. but Introns Are Conserved © Jones• The rules & relateBartlett to genomic Learning, characteristics, LLC or ©• UnderJones positive & Bartlett selection an Learning, individual with LLC an NOT“ pressures,”FOR SALE that constitute OR DISTRIBUTION the genome phenotype. NOT advantageous FOR SALE mutation OR survives DISTRIBUTION (i.e., is able to 4.4 produce more fertile progeny) relative to others Organization of Interrupted Genes May Be without the mutation. Conserved • Due to intrinsic genomic pressures, such as that which • Introns can be detected when genes are compared with conserves the potential to extrude stem-loops from du- their RNA transcription products by either restriction plex DNA, introns evolve more slowly than exons that © Jones & Bartlettmapping, Learning, electron microscopy,LLC or sequencing. © Jones & Bartlettare under Learning, positive selection LLC pressure. NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 8181 © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. © Jones & BartlettCHAPTER Learning, OUTLINE, CONTINUEDLLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION 4.7 Genes Show a Wide Distribution of Sizes Due • The exons of some genes appear homologous to the exons of others, suggesting a common exon Primarily to Intron Size and Number Variation ancestry. • Most genes are uninterrupted in Saccharomyces cerevisiae but are interrupted© in Jonesmulticellular & eukaryotes.Bartlett Learning, LLC4.10 Members of a Gene Family© Jones Have a Common& Bartlett Learning, LLC • Exons are usually short,NOT typically FOR encodingSALE fewerOR thanDISTRIBUTION Organization NOT FOR SALE OR DISTRIBUTION 100 amino acids. • A set of homologous genes should share common • Introns are short in unicellular/oligocellular eukary- features that preceded their evolutionary separation. otes but can be many kilobases (kb) in multicellular • All globin genes have a common form of organization eukaryotes. with three exons and two introns, suggesting that they • The overall length of a gene is determined largely by are descended from a single ancestral gene. ©its Jones introns. & Bartlett Learning, LLC • Intron© Jones positions & in Bartlettthe actin gene Learning, family are highly LLC variable, which suggests that introns do not separate 4.8 SomeNOT DNA FOR Sequences SALE Encode OR DISTRIBUTIONMore Than One NOT FOR SALE OR DISTRIBUTION functional domains. Polypeptide 4.11 There Are Many Forms of Information in DNA • The use of alternative initiation or termination codons allows multiple variants of a polypeptide chain. • Genetic information includes not only that related to • Different polypeptides can be produced from the same characters corresponding to the conventional pheno- © Jones & Bartlettsequence Learning, of DNA when theLLC mRNA is read in different © Jones & Bartletttype, but also Learning, that related to LLC characters (pressures) NOT FOR SALEreading OR frames DISTRIBUTION (as two overlapping genes). NOT FOR SALEcorresponding OR DISTRIBUTION to the genome “phenotype.” • Otherwise identical polypeptides, differing by the • In certain contexts, the definition of the gene can be presence or absence of certain regions, can be gener- seen as reversed from “one gene–one protein” to “one ated by differential (alternative) splicing when certain protein–one gene.” exons are included or excluded. This may take the form • Positional information may be important in of including or excluding individual exons, or of choos- development. ing between alternative© Jones exons. & Bartlett Learning, LLC • Sequences transferred ©“horizontally” Jones & from Bartlett other Learning, LLC species to the germline could land in introns or 4.9 Some Exons Can BeNOT Equated FOR with SALE Protein ORFunctional DISTRIBUTION NOT FOR SALE OR DISTRIBUTION intergenic DNA and then transfer “vertically” through Domains the generations. Some of these sequences may be • Proteins can consist of independent functional mod- involved in intracellular nonself-recognition. ules, the boundaries of which, in some cases, can be 4.12 Summary equated with those of exons. © Jones & Bartlett Learning, LLC © Jones & Bartlett Learning, LLC NOT FOR SALE OR DISTRIBUTION NOT FOR SALE OR DISTRIBUTION is operational with respect to phenotype. 4.1 Introduction Protein-encoding sequences can be inter- The simplest form of a gene is a length of DNA rupted, as can the 59 and 39 sequences (UTRs) © Jones & Bartlett Learning,that directly LLC corresponds to its polypeptide© Jones & Bartlettthat flank Learning, the protein-encoding LLC sequences NOT FOR SALE OR DISTRIBUTION product. Bacterial genes are almost NOTalways FOR of SALEwithin OR mRNA. DISTRIBUTION The interrupting sequences this type, in which a continuous sequence of are removed from the primary (RNA) 3N bases encodes a polypeptide of N amino transcript (or pre-mRNA) during gene acids. However, in eukaryotes ribosomal RNAs expression, generating an mRNA that includes (rRNAs), transfer RNAs (tRNAs), and mes- a continuous base sequence corresponding to senger© Jones RNAs (mRNAs)& Bartlett are Learning, first synthesized LLC the polypeptide product© Jones as determined & Bartlett by Learning,the LLC as longNOT precursor FOR SALE transcripts OR DISTRIBUTION that are subse- genetic code. The sequencesNOT FOR of SALEDNA compris OR DISTRIBUTION- quently shortened (see the chapter titled RNA ing an interrupted protein-encoding gene are Splicing and Processing). Thus eukaryotic genes divided into the two categories depicted in are much longer than the functional transcripts FIGURE 4.1: they produce. It is reasonable to assume that • Exons are the sequences retained in the © Jones &the Bartlett shortening Learning, involved LLC a trimming of addi- © Jonesmature & RNABartlett product. Learning, A mature LLC tran- NOT FOR SALEtional, perhapsOR DISTRIBUTION regulatory, sequences at the NOT scriptFOR SALEstarts and OR ends DISTRIBUTION with exons that 59 and/or 39 ends of transcripts, leaving the correspond to the 59 and 39 ends of the rRNA or protein-encoding sequence of the RNA. precursor intact. • Introns are the intervening sequences However, as it happens a eukaryotic that are removed when the primary © Jones & Bartlett Learning,gene can LLC include additional sequences© Jones that & BartlettRNA Learning, transcript LLCis processed to give the NOT FOR SALE OR DISTRIBUTIONlie both within and outside the regionNOT thatFOR SALE ORmature DISTRIBUTION RNA product. 82 CHAPTER 4 The Interrupted Gene © Jones & Bartlett Learning, LLC. NOT FOR SALE OR DISTRIBUTION. The exon sequences are in the same order in EXON 1 EXON 2 EXON 3 © Jones the& Bartlett gene and Learning,in the RNA, butLLC an interrupted DNA© Jones &INTRON Bartlett 1 Learning,INTRON LLC 2 NOT FORgene SALE is longer OR DISTRIBUTION than its mature RNA product NOT FOR SALE OR DISTRIBUTION because of the presence of the introns. RNA synthesis pre-mRNA The processing of interrupted genes INTRON 1 INTRON 2 requires an additional