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