Genomes and their Evolution

Comparisons of genomes among organisms provide information about the evolutionary history of genes and taxonomic groups

What genomic information distinguishes a human from a chimpanzee?

New approaches have accelerated the pace of genome sequencing

Cut the DNAinto overlappingfragments short enoughfor sequencing

1

2

3

4

Clone the fragmentsin plasmid or phagevectors.

Sequence eachfragment.

Order thesequences intoone overallsequencewith computer software.

Whole-Genome Shotgun Approach

to Genome

Sequencing- developed by Craig

Venter

Scientists use bioinformatics to analyze genomes and their functions

Bioinformatics resources are provided by a number of sources

Comparison of sequences of “new” genes with those of known genes in other species may help identify new genes

Most recentcommonancestorof all livingthings

Billions of years ago4 3 2 1 0

Bacteria

Eukarya

Archaea

Chimpanzee

Human

Mouse

010203040506070Millions of years ago

Genome comparisons of closely related species help us understand recent evolutionary events

Translation andribosomal functions

Nuclear-cytoplasmic

transport

RNA processing

Transcriptionand chromatin-

related functions

Mitochondrialfunctions

Nuclear migrationand proteindegradation

Mitosis

DNA replicationand repair

Cell polarity andmorphogenesis

Protein folding,glycosylation, and

cell wall biosynthesis

Secretionand vesicletransport

Metabolismand amino acid

biosynthesis

Peroxisomalfunctions

Glutamatebiosynthesis

Serine-related

biosynthesis

Amino acidpermease pathway

Vesiclefusion

Understanding Genes and Gene Expression at the

Systems Level

Danny Hillis Ted TalkStart at 8 minutes

By summer of 2007, the sequencing of more than 600 genomes hadbeen completed.

Fig. 21-7Exons (regions of genes coding for protein

or giving rise to rRNA or tRNA) (1.5%)

RepetitiveDNA thatincludestransposableelementsand relatedsequences(44%)

Introns andregulatorysequences(24%)

UniquenoncodingDNA (15%)

RepetitiveDNAunrelated totransposableelements (15%)

L1sequences(17%)

Alu elements(10%)

Simple sequenceDNA (3%)

Large-segmentduplications (5–6%)

•Eukaryotic genomes are larger and have more protein-coding genes.•Eukaryotic genomes have more regulatory sequences. Greater complexity requires more regulation. •Much of eukaryotic DNA is noncoding, including introns, gene control sequences, and repeated sequences.

Transposable Elements

• The first evidence for wandering DNA segments– Came from

geneticist Barbara McClintock’s breeding experiments with Indian corn

Nobel Prize 1983

TransposonNew copy of transposon

Insertion

Transposonis copied

Mobile transposon

DNA ofgenome

(a) Transposon movement (“copy-and-paste” mechanism)

RetrotransposonNew copy of

retrotransposon

Insertion

Reversetranscriptase

RNA

(b) Retrotransposon movement

Transposons, move by means of a DNA intermediate

Retrotransposons move by means of an RNA intermediate

The transposable element can alter the expression of a gene at the new location

How Transposable Elements Contribute to Genome Evolution

• Movement of transposable elements– Occasionally generates new sequence combinations that

are beneficial to the organism

• Some mechanisms– Can alter the functions of genes or their patterns of

expression and regulation

Alu inserts as markers of primate evolution(retrotransposon)

Salem, et al. 2003. PNAS 100:12787-12791

Genes and Multigene Families

• Many eukaryotic genes are present in one copy per haploid set of chromosomes

• The rest of the genome occurs in multigene families, collections of identical or very similar genes

• Some multigene families consist of identical DNA sequences, usually clustered tandemly, such as those that code for RNA products.

Fig. 21-10a

(a) Part of the ribosomal RNA gene family

18S

28S

28S18S 5.8S

5.8S

rRNA

DNA

DNARNA transcripts

Nontranscribedspacer Transcription unit

Heme

Hemoglobin

-Globin

-Globin

-Globin gene family-Globin gene family

Chromosome 16 Chromosome 11

2 1

2

1

G A

Embryo Embryo FetusFetus

and adult Adult

α-globins and β-globins are examples of multigene families of nonidentical genes

Figure 21.14

Duplication ofancestral gene

Mutation inboth copies

Transposition todifferent chromosomes

Further duplicationsand mutations

Ancestral globin gene

-Globin gene familyon chromosome 16

-Globin gene familyon chromosome 11

Evo

luti

on

ary

tim

e

2

1

2 1 G A

ICE FISH GENE DUPLICATION EVOLUTIONARY HISTORYCLIP

Alterations of Chromosome Structure

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

Humans have 23 pairs of chromosomes, while chimpanzees have 24 pairsChromosomal rearrangements are thought to contribute to the generation of new species

Most recentcommonancestorof all livingthings

Billions of years ago4 3 2 1 0

Bacteria

Eukarya

Archaea

Chimpanzee

Human

Mouse

010203040506070Millions of years ago

The accumulation of changes in the genomeprovides a record of evolutionary history

Comparing Genomes Within a Species

• As a species, humans have only been around about 200,000 years and have low within-species genetic variation

• Variation within humans is due to single nucleotide polymorphisms, inversions, deletions, and duplications

• These variations are useful for studying human evolution and human health

Other Repetitive DNA, Including Simple Sequence DNA

• Simple sequence DNA contains many copies of tandemly repeated short sequences

This repeat number can vary from person to person, producing variation useful inforensic science.

STRBase: a short tandem repeat DNA database for the human identity testing community

Christian M. Ruitberg, Dennis J. Reeder and John M. Butler*

Biotechnology Division, National Institute of Standards and Technology, 100 Bureau Drive, Mail Stop 8311, Gaithersburg, MD 20899-8311, USA

AbstractThe National Institute of Standards and Technology (NIST) has compiled and maintained a Short Tandem Repeat DNA Internet Database (http://www.cstl.nist.gov/biotech/strbase/) since 1997 commonly referred to as STRBase. This database is an information resource for the forensic DNA typing community with details on commonly used short tandem repeat (STR) DNA markers.From: Nucl. Acids Res. (2001) 29 (1): 320-322.

Comparing Developmental Processes

• Evolutionary developmental biology, or evo-devo, is the study of the evolution of developmental processes in multicellular organisms

• Genomic information shows that minor differences in gene sequence or regulation can result in major differences in form

Adultfruit fly

Fruit fly embryo(10 hours)

Flychromosome

Mousechromosomes

Mouse embryo(12 days)

Adult mouse

Molecular analysis of the homeotic genes in Drosophila has shown that they all include a sequence called a homeobox

Hox genes

Neil Shubin and Sean CarrollDiscuss homeobox genes

GHOSTS

Fig. 21-3-1Cut the DNAinto overlappingfragments short enoughfor sequencing

1

2 Clone the fragmentsin plasmid or phagevectors.

Whole-Genome Shotgun Approach to Genome Sequencing- developed by Craig Venter

Fig. 21-3-2Cut the DNAinto overlappingfragments short enoughfor sequencing

1

2

3

Clone the fragmentsin plasmid or phagevectors.

Sequence eachfragment.

Fig. 21-2-1Cytogenetic map

Genes locatedby FISH

Chromosomebands

Three-Stage Approach to Genome Sequencing

Fig. 21-2-2Cytogenetic map

Genes locatedby FISH

Chromosomebands

Linkage mapping1

Geneticmarkers

Fig. 21-2-3Cytogenetic map

Genes locatedby FISH

Chromosomebands

Linkage mapping1

2

Geneticmarkers

Physical mapping

Overlappingfragments

Fig. 21-2-4Cytogenetic map

Genes locatedby FISH

Chromosomebands

Linkage mapping1

2

3

Geneticmarkers

Physical mapping

Overlappingfragments

DNA sequencing

From: National Academy of Science, 2009

Metagenomics

Genetic diversity is explored without isolating intact organisms.