Chapter 21: Genomes & Their Evolution

Chapter 21:Genomes & Their Evolution1. Sequencing & Analyzing Genomes2. How Genomes Evolve

1. Sequencing & AnalyzingGenomesChapter Reading – pp. 437-447

Whole Genome Shotgun Sequencing1 Cut the DNA intooverlapping fragments short enoughfor sequencing.2 Clone the fragmentsin plasmid or phagevectors.3 Sequence eachfragment.4 Order thesequences intoone overallsequencewith computersoftware.

BioinformaticsBioinformatics refers to application of statistics andcomputer analysis to DNA, protein sequence data. computeranalysis canidentify proteincoding regionsin DNA,determine aminoacid sequences,comparesequencesamong species,etc

Relative GenomeSizeGenome size and genenumber do not correlateat all with organismcomplexity. alternative splicing of genesand the repertoire of noncoding RNAs (e.g., miRNA)may be a better indicatorof “sophistication” orcomplexity in a species

Types of Human DNA ElementsMost of thehuman genome(and that ofmany otherspecies) doesnot code for anyobvious geneproducts andhas a functionthat is as yetunclear.

Repetitive DNA ElementsMuch of the human genome consists ofrepetitive DNA sequences that are thought toultimately be of viral origin.Transposable Elements DNA segments that are duplicated and distributedthroughout the genomeAlu elements repetitive DNA sequences containing the Alu Irestriction enzyme sitesShort tandem repeats (STRs) very short sequences repeated over and over

Transposable ElementsBarbara McClintock proposed the concept of“jumping genes” in the 1950s based on herstudies of corn which was not taken seriously.Much later theexistence oftransposableelements that could“jump” in thegenome validatedher observations.

TransposonsTransposonDNA ofgenomeTransposonis copiedNew copy oftransposonInsertionMobile transposonMobile DNA elements that can be copied & insertedElsewhere in the genome. the transposon encodes the enzyme transposase which cancopy transposon sequence and randomly insert elsewhere

RetrotransposonsRetrotransposons are much like transposons except thatthey encode reverse transcriptase and have anRNA intermediate in the process.New copy ofRetrotransposonretrotransposonFormation of asingle-strandedRNA intermediateRNAInsertionReversetranscriptase

Multigene FamiliesMany genes are actually part of a group orcluster of similar genes referred to as a“multigene family”. 2 or more genes with nearly identical or verysimilar sequences thought to have arisen due to gene duplicationand subsequent mutation members of a multigene family are typicallysimilar in function as well as sequence arrangement of genes in multigene families alsoprovides evidence of similar origins

b-Globina-GlobinHemea-Globin gene familyb-Globin gene familyChromosome 11Chromosome 16zEmbryoyz ya2ya1a2a1yqFetusand adulteEmbryoGgAgFetus(b) The human a-globin and b-globin gene familiesybdAdultb

2. How Genomes EvolveChapter Reading – pp. 448-458

Rearrangement of GenomesGenomes can undergo a number of large-scalechanges that can lead to significant changes ingenetic structure and in gene products:Chromosomal rearrangement breaking and recombining of pieces of diff. chrom.Transposition of mobile DNA elements sequences that can move around the genomeGene duplication duplication of gene sequencesExon shuffling combining of exons from different genes

Changes in Chromosome StructureHuman chromosome 2 is clearly a combination ofchimpanzee chromosomes 12 & 13.Humanchromosome equencesTelomere-likesequences12Humanchromosome 16Centromere-likesequences13(a) Human and chimpanzee chromosomesBlocks of genes in miceand humans haveremained intact thoughthey are distributeddifferently amongchromosomes.Mousechromosomes78(b) Human and mouse chromosomes1617

Evolution of Novel GenesGenes encoding proteins with entirely newfunctions can arise by:1) Duplication of existing gene followed bymutation producing distinct gene product the 2 genes will share significant homologyhowever may have very different functions(e.g., lysozyme and a-lactalbumin)2) Exon shuffling errors in meiotic recombination or transposition cancause the addition or loss of exons from similar orvery different genes

Gene Duplication & Crossing OverNonsister GenechromatidsIncorrect pairingof two homologsduring nment ofsimilar DNAsequencesduring meioticcrossing overcan result inchromosomeswith duplicated(or missing)regions of DNA.

Duplication followed by Mutationlysozyme vs a-lactalbumin

Model for Globin Gene DuplicationThe globin gene families show evidence of duplication.Ancestral globin geneEvolutionary timeDuplication ofancestral geneMutation inboth copiesaTransposition todifferent chromosomesFurther duplicationsand mutationsbaazzbyz ya ya a2 a1 yq21a-Globin gene familyon chromosome 16egeGgbAgybdb-Globin gene familyon chromosome 11b

Globin Gene ComparisonOver time apparently duplicated globin genesdiverged via mutation into similar yet distinctproteins with similar yet unique functions.

Exon ShufflingEGFEGFEGFEGFEpidermal growthfactor gene with multipleEGF exonsFFFExonshufflingExonduplicationFFibronectin gene with multiple“finger” exonsFEGFKKKPlasminogen gene with a“kringle” exonPortions of ancestral genesExonshufflingTPA gene as it exists today

Comparing GenomesBacteriaMost recentcommonancestorof all livingthingsEukaryaArchaea4132Billions of years ago0ChimpanzeeHumanMouse706050403020Millions of years ago100Sequencehomology andgenome structurereflectevolutionaryrelatedness: degree ofdifferences ingene sequences,chromosome &gene structuresallow estimationof time since acommon ancestor

Key Terms for Chapter 21 whole genome shotgun seq. bioinformatics transposable elements: transposons , transposase,retrotransposons gene duplication, exon shufflingRelevant Chapter Questions: 1-6

Chapter 21: Genomes & Their Evolution 1. Sequencing & Analyzing Genomes 2. How Genomes Evolve. 1. Sequencing & Analyzing Genomes Chapter Reading – pp. 437-447. Whole Genome Shotgun Sequencing Cut the DNA into overlapping frag-ments short enough for sequencing. 1 Clone the fragments in plasmid or phage vectors. 2 Sequence each