Chapter 21:Genomes & Their Evolution
1. Sequencing & Analyzing Genomes
2. How Genomes Evolve
1. Sequencing & AnalyzingGenomes
Chapter Reading – pp. 437-447
Whole Genome Shotgun SequencingCut the DNA intooverlapping frag-ments short enoughfor sequencing.
1
Clone the fragmentsin plasmid or phagevectors.
2
Sequence eachfragment.
3
Order thesequences intoone overallsequencewith computersoftware.
4
BioinformaticsBioinformatics refers to application of statistics and computer analysis to DNA, protein sequence data.
• computer analysis can identify protein coding regions in DNA, determine amino acid sequences,compare sequences among species, etc…
Relative GenomeSize
Genome size and gene number do not correlate at all with organism complexity.
• alternative splicing of genesand the repertoire of non-coding RNAs (e.g., miRNA)may be a better indicator of “sophistication” or complexity in a species
Types of Human DNA Elements
Most of the human genome(and that of many other species) does not code for any obvious gene products and has a function that is as yet unclear.
Repetitive DNA ElementsMuch of the human genome consists of repetitive DNA sequences that are thought to ultimately be of viral origin.
Transposable Elements• DNA segments that are duplicated and distributed
throughout the genome
Alu elements• repetitive DNA sequences containing the Alu Irestriction enzyme sites
Short tandem repeats (STRs)• very short sequences repeated over and over
Transposable ElementsBarbara McClintock proposed the concept of “jumping genes” in the 1950s based on her studies of corn which was not taken seriously.
Much later the existence of transposable elements that could “jump” in the genome validated her observations.
Transposons
• the transposon encodes the enzyme transposase which can copy transposon sequence and randomly insert elsewhere
Mobile DNA elements that can be copied & insertedElsewhere in the genome.
Transposon
Transposonis copied
DNA ofgenome
Mobile transposon
Insertion
New copy oftransposon
RetrotransposonNew copy of
retrotransposon
Insertion
Reversetranscriptase
RNA
Formation of asingle-stranded
RNA intermediate
RetrotransposonsRetrotransposons are much like transposons except that they encode reverse transcriptase and have anRNA intermediate in the process.
Multigene FamiliesMany genes are actually part of a group or cluster 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 typically similar in function as well as sequence• arrangement of genes in multigene families alsoprovides evidence of similar origins
a-Globin
a-Globin gene familyChromosome 16
b-Globin gene familyChromosome 11
b-Globin
Heme
z yz ya2ya
1a2 a1 yq e Gg Ag yb d b
EmbryoFetus
and adult Fetus AdultEmbryo
(b) The human a-globin and b-globin gene families
2. How Genomes EvolveChapter Reading – pp. 448-458
Rearrangement of GenomesGenomes can undergo a number of large-scale changes that can lead to significant changes in genetic structure and in gene products:
Chromosomal rearrangement
Transposition of mobile DNA elements
Gene duplication
Exon shuffling
• breaking and recombining of pieces of diff. chrom.
• sequences that can move around the genome
• duplication of gene sequences
• combining of exons from different genes
Changes in Chromosome StructureHuman chromosome 2 is clearly a combination of chimpanzee chromosomes 12 & 13.
Humanchromosome 2
Telomeresequences
Centromeresequences
Chimpanzeechromosomes
12Telomere-likesequences
Centromere-likesequences
Humanchromosome 16
13
(a) Human and chimpanzee chromosomes (b) Human and mouse chromosomes
7 8 16 17
Mousechromosomes
Blocks of genes in mice and humans have
remained intact though they are distributed differently among
chromosomes.
Evolution of Novel GenesGenes encoding proteins with entirely new functions can arise by:
1) Duplication of existing gene followed bymutation producing distinct gene product• the 2 genes will share significant homology however 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
Nonsisterchromatids
Gene Transposableelement
Crossoverpoint
and
Incorrect pairingof two homologsduring meiosis
Gene Duplication & Crossing Over
Misalignment of similar DNA sequences during meiotic crossing over can result in chromosomes with 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 gene
a-Globin gene familyon chromosome 16
b-Globin gene familyon chromosome 11
Duplication ofancestral gene
Mutation inboth copies
Transposition todifferent chromosomesFurther duplicationsand mutations
Evol
utio
nary
tim
e
z
b
b
a b
e g
a
az
yqyz ya2ya
1a2 a1 be Gg Ag yb d
Globin Gene Comparison
Over time apparently duplicated globin genes diverged via mutation into similar yet distinct proteins with similar yet unique functions.
Exonduplication
Exonshuffling
Exonshuffling
F EGF K K
K
F F F F
EGF EGF EGF EGFEpidermal growthfactor gene with multipleEGF exons
Fibronectin gene with multiple“finger” exons
Plasminogen gene with a“kringle” exon
Portions of ancestral genes TPA gene as it exists today
Exon Shuffling
Comparing GenomesSequence homology and genome structure reflect evolutionaryrelatedness:
• degree of differences ingene sequences,chromosome & gene structuresallow estimation of time since a common ancestor
Most recentcommonancestorof all livingthings
Bacteria
Eukarya
Archaea
Chimpanzee
Human
Mouse
Millions of years ago
Billions of years ago4 3 2
010203040506070
01
Key Terms for Chapter 21
• transposable elements: transposons , transposase, retrotransposons
• whole genome shotgun seq.• bioinformatics
• gene duplication, exon shuffling
Relevant Chapter Questions: 1-6