Genomes and Their Evolution - Home | Ms. R. R. Wingerden · 6 Copyright © 2008 Pearson Education...

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Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

PowerPoint® Lecture Presentations for

BiologyEighth Edition

Neil Campbell and Jane Reece

Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

Chapter 21

Genomes and Their Evolution

Copyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Overview: Reading the Leaves from the Tree ofLife

• Complete genome sequences exist for ahuman, chimpanzee, E. coli, brewer’s yeast,nematode, fruit fly, house mouse, rhesusmacaque, and other organisms

• Comparisons of genomes among organismsprovide information about the evolutionaryhistory of genes and taxonomic groups


• Genomics is the study of whole sets of genesand their interactions

• Bioinformatics is the application ofcomputational methods to the storage andanalysis of biological data

Fig. 21-1


Concept 21.1: New approaches have acceleratedthe pace of genome sequencing

• The most ambitious mapping project to datehas been the sequencing of the humangenome

• Officially begun as the Human GenomeProject in 1990, the sequencing was largelycompleted by 2003

• The project had three stages:– Genetic (or linkage) mapping

– Physical mapping

– DNA sequencingCopyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

Three-Stage Approach to Genome Sequencing

• A linkage map (genetic map) maps thelocation of several thousand genetic markerson each chromosome

• A genetic marker is a gene or other identifiableDNA sequence

• Recombination frequencies are used todetermine the order and relative distancesbetween genetic markers

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Fig. 21-2-1Cytogenetic map

Genes locatedby FISH

Chromosomebands



Chromosomebands

Linkage mapping1

Geneticmarkers



Chromosomebands

Linkage mapping1

2

Geneticmarkers

Physical mapping

Overlappingfragments



Chromosomebands

Linkage mapping1

2

3

Geneticmarkers

Physical mapping

Overlappingfragments

DNA sequencing


• A physical map expresses the distancebetween genetic markers, usually as thenumber of base pairs along the DNA

• It is constructed by cutting a DNA molecule intomany short fragments and arranging them inorder by identifying overlaps


• Sequencing machines are used to determinethe complete nucleotide sequence of eachchromosome

• A complete haploid set of humanchromosomes consists of 3.2 billion base pairs

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Whole-Genome Shotgun Approach to GenomeSequencing

• The whole-genome shotgun approach wasdeveloped by J. Craig Venter in 1992

• This approach skips genetic and physicalmapping and sequences random DNAfragments directly

• Powerful computer programs are used to orderfragments into a continuous sequence

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

1

2 Clone the fragmentsin plasmid or phagevectors.


1

2

3

Clone the fragmentsin plasmid or phagevectors.

Sequence eachfragment.


1

2

3

4

Clone the fragmentsin plasmid or phagevectors.

Sequence eachfragment.

Order thesequences intoone overallsequencewith computer software.


• Both the three-stage process and the whole-genome shotgun approach were used for theHuman Genome Project and for genomesequencing of other organisms

• At first many scientists were skeptical aboutthe whole-genome shotgun approach, but it isnow widely used as the sequencing method ofchoice

• A hybrid of the two approaches may be themost useful in the long run


Concept 21.2 Scientists use bioinformatics toanalyze genomes and their functions

• The Human Genome Project establisheddatabases and refined analytical software tomake data available on the Internet

• This has accelerated progress in DNAsequence analysis

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Centralized Resources for Analyzing GenomeSequences

• Bioinformatics resources are provided by anumber of sources:

– National Library of Medicine and the NationalInstitutes of Health (NIH) created the NationalCenter for Biotechnology Information (NCBI)

– European Molecular Biology Laboratory

– DNA Data Bank of Japan


• Genbank, the NCBI database of sequences,doubles its data approximately every 18 months

• Software is available that allows online visitors tosearch Genbank for matches to:

– A specific DNA sequence

– A predicted protein sequence

– Common stretches of amino acids in a protein

• The NCBI website also provides 3-D views of allprotein structures that have been determined

Fig. 21-4


Identifying Protein-Coding Genes Within DNASequences

• Computer analysis of genome sequenceshelps identify sequences likely to encodeproteins

• Comparison of sequences of “new” genes withthose of known genes in other species mayhelp identify new genes


Understanding Genes and Their Products at theSystems Level

• Proteomics is the systematic study of allproteins encoded by a genome

• Proteins, not genes, carry out most of theactivities of the cell


How Systems Are Studied: An Example

• A systems biology approach can be applied todefine gene circuits and protein interactionnetworks

• Researchers working on Drosophila usedpowerful computers and software to predict4,700 protein products that participated in4,000 interactions

• The systems biology approach is possiblebecause of advances in bioinformatics

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Fig. 21-5

Proteins


Application of Systems Biology to Medicine

• A systems biology approach has severalmedical applications:

– The Cancer Genome Atlas project is currentlymonitoring 2,000 genes in cancer cells forchanges due to mutations and rearrangements

– Treatment of cancers and other diseases canbe individually tailored following analysis ofgene expression patterns in a patient

– In future, DNA sequencing may highlightdiseases to which an individual is predisposed

Fig. 21-6


Concept 21.3 Genomes vary in size, number ofgenes, and gene density

• By summer 2007, genomes had beensequenced for 500 bacteria, 45 archaea, and65 eukaryotes including vertebrates,invertebrates, and plants


Genome Size

• Genomes of most bacteria and archaea rangefrom 1 to 6 million base pairs (Mb); genomes ofeukaryotes are usually larger

• Most plants and animals have genomesgreater than 100 Mb; humans have 3,200 Mb

• Within each domain there is no systematicrelationship between genome size andphenotype

Table 21-1

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Number of Genes

• Free-living bacteria and archaea have 1,500 to7,500 genes

• Unicellular fungi have from about 5,000 genesand multicellular eukaryotes from 40,000 genes


• Number of genes is not correlated to genomesize

• For example, it is estimated that the nematodeC. elegans has 100 Mb and 20,000 genes, whilehumans have 3,200 Mb and 20,488 genes

• Vertebrate genomes can produce more than onepolypeptide per gene because of alternativesplicing of RNA transcripts


Gene Density and Noncoding DNA

• Humans and other mammals have the lowestgene density, or number of genes, in a givenlength of DNA

• Multicellular eukaryotes have many intronswithin genes and noncoding DNA betweengenes


Concept 21.4: Multicellular eukaryotes have muchnoncoding DNA and many multigene families

• The bulk of most eukaryotic genomes consistsof noncoding DNA sequences, often describedin the past as “junk DNA”

• Much evidence indicates that noncoding DNAplays important roles in the cell

• For example, genomes of humans, rats, andmice show high sequence conservation forabout 500 noncoding regions

• Sequencing of the human genome reveals that98.5% does not code for proteins, rRNAs, ortRNAs


• About 24% of the human genome codes forintrons and gene-related regulatory sequences

• Intergenic DNA is noncoding DNA foundbetween genes– Pseudogenes are former genes that have

accumulated mutations and are nonfunctional

– Repetitive DNA is present in multiple copies inthe genome

• About three-fourths of repetitive DNA is madeup of transposable elements and sequencesrelated to them

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%)

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Transposable Elements and Related Sequences

• The first evidence for wandering DNAsegments came from geneticist BarbaraMcClintock’s breeding experiments with Indiancorn

• McClintock identified changes in the color ofcorn kernels that made sense only bypostulating that some genetic elements movefrom other genome locations into the genes forkernel color

• These transposable elements move from onesite to another in a cell’s DNA; they are presentin both prokaryotes and eukaryotes

Fig. 21-8


Movement of Transposons and Retrotransposons

• Eukaryotic transposable elements are of twotypes:

– Transposons, which move within a genomeby means of a DNA intermediate

– Retrotransposons, which move by means ofan RNA intermediate

Fig. 21-9

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


Sequences Related to Transposable Elements

• Multiple copies of transposable elements andrelated sequences are scattered throughoutthe eukaryotic genome

• In primates, a large portion of transposableelement–related DNA consists of a family ofsimilar sequences called Alu elements

• Many Alu elements are transcribed into RNAmolecules; however, their function is unknown


• The human genome also contains manysequences of a type of retrotransposon calledLINE-1 (L1)

• L1 sequences have a low rate of transpositionand may help regulate gene expression

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Other Repetitive DNA, Including Simple SequenceDNA

• About 15% of the human genome consists ofduplication of long sequences of DNA from onelocation to another

• In contrast, simple sequence DNA containsmany copies of tandemly repeated shortsequences


• A series of repeating units of 2 to 5 nucleotidesis called a short tandem repeat (STR)

• The repeat number for STRs can vary amongsites (within a genome) or individuals

• Simple sequence DNA is common incentromeres and telomeres, where it probablyplays structural roles in the chromosome


Genes and Multigene Families

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

• The rest of the genome occurs in multigenefamilies, collections of identical or very similargenes

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

Fig. 21-10

DNARNA transcripts

Nontranscribedspacer Transcription unit

18S

28S

5.8S 28S

5.8S

rRNA

18S

DNA

(a) Part of the ribosomal RNA gene family

Heme

Hemoglobin

β-Globin

α-Globin

α-Globin gene family β-Globin gene family

Chromosome 16 Chromosome 11

ζ Ψζ Ψα2Ψα1

α2 α1 Ψθ ε Gγ Aγ Ψβ δ β

AdultFetusEmbryoFetus

and adultEmbryo

(b) The human α-globin and β-globin gene families

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


• The classic examples of multigene families ofnonidentical genes are two related families ofgenes that encode globins

• α-globins and β-globins are polypeptides ofhemoglobin and are coded by genes ondifferent human chromosomes

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Fig. 21-10b

(b) The human α-globin and β-globin gene families

Heme

Hemoglobin

α-Globin

β-Globin

β-Globin gene familyα-Globin gene family

Chromosome 16 Chromosome 11

α2 α1ζ Ψζ Ψα2Ψα1

Ψθ ε Gγ Aγ Ψβ δ β

Embryo Embryo FetusFetus

and adult Adult


Concept 21.5: Duplication, rearrangement, andmutation of DNA contribute to genome evolution

• The basis of change at the genomic level ismutation, which underlies much of genomeevolution

• The earliest forms of life likely had a minimalnumber of genes, including only thosenecessary for survival and reproduction

• The size of genomes has increased overevolutionary time, with the extra geneticmaterial providing raw material for genediversification


Duplication of Entire Chromosome Sets

• Accidents in meiosis can lead to one or moreextra sets of chromosomes, a condition knownas polyploidy

• The genes in one or more of the extra sets candiverge by accumulating mutations; thesevariations may persist if the organism carryingthem survives and reproduces


Alterations of Chromosome Structure

• Humans have 23 pairs of chromosomes, whilechimpanzees have 24 pairs

• Following the divergence of humans andchimpanzees from a common ancestor, twoancestral chromosomes fused in the human line

• Duplications and inversions result from mistakesduring meiotic recombination

• Comparative analysis between chromosomes ofhumans and 7 mammalian species paints ahypothetical chromosomal evolutionary history

Fig. 21-11

Human chromosome 16

Blocks of DNAsequence

Blocks of similar sequences in four mouse chromosomes:

7 816

17


• The rate of duplications and inversions seems tohave accelerated about 100 million years ago

• This coincides with when large dinosaurs wentextinct and mammals diversified

• Chromosomal rearrangements are thought tocontribute to the generation of new species

• Some of the recombination “hot spots”associated with chromosomal rearrangementare also locations that are associated withdiseases

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Duplication and Divergence of Gene-Sized Regionsof DNA

• Unequal crossing over during prophase I ofmeiosis can result in one chromosome with adeletion and another with a duplication of aparticular region

• Transposable elements can provide sites forcrossover between nonsister chromatids

Fig. 21-12

Transposableelement

Gene

Nonsisterchromatids

Crossover

Incorrect pairingof two homologsduring meiosis

and


Evolution of Genes with Related Functions: TheHuman Globin Genes

• The genes encoding the various globinproteins evolved from one common ancestralglobin gene, which duplicated and divergedabout 450–500 million years ago

• After the duplication events, differencesbetween the genes in the globin family arosefrom the accumulation of mutations

Fig. 21-13

Ancestral globin gene

Duplication ofancestral gene

Mutation inboth copies

Transposition todifferent chromosomes

Further duplicationsand mutations

α-Globin gene familyon chromosome 16

β-Globin gene familyon chromosome 11

Evol

utio

nary

tim

e α

α

α

α2 α1

β

β

β

β

ζ

ζ Ψζ Ψα2Ψα1

Ψθ

ε

ε

γ

Gγ Aγ Ψβ δ


• Subsequent duplications of these genes andrandom mutations gave rise to the presentglobin genes, which code for oxygen-bindingproteins

• The similarity in the amino acid sequences ofthe various globin proteins supports this modelof gene duplication and mutation

Table 21-2

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Evolution of Genes with Novel Functions

• The copies of some duplicated genes havediverged so much in evolution that thefunctions of their encoded proteins are nowvery different

• For example the lysozyme gene wasduplicated and evolved into the α-lactalbumingene in mammals

• Lysozyme is an enzyme that helps protectanimals against bacterial infection

• α-lactalbumin is a nonenzymatic protein thatplays a role in milk production in mammals


Rearrangements of Parts of Genes: ExonDuplication and Exon Shuffling

• The duplication or repositioning of exons hascontributed to genome evolution

• Errors in meiosis can result in an exon beingduplicated on one chromosome and deletedfrom the homologous chromosome

• In exon shuffling, errors in meioticrecombination lead to some mixing andmatching of exons, either within a gene orbetween two nonallelic genes

Fig. 21-14

Epidermal growthfactor gene with multipleEGF exons (green)

Fibronectin gene with multiple“finger” exons (orange)

Exonshuffling

Exonshuffling

Exonduplication

Plasminogen gene with a“kringle” exon (blue)

Portions of ancestral genes TPA gene as it exists todayCopyright © 2008 Pearson Education Inc., publishing as Pearson Benjamin Cummings

How Transposable Elements Contribute toGenome Evolution

• Multiple copies of similar transposableelements may facilitate recombination, orcrossing over, between different chromosomes

• Insertion of transposable elements within aprotein-coding sequence may block proteinproduction

• Insertion of transposable elements within aregulatory sequence may increase or decreaseprotein production


• Transposable elements may carry a gene orgroups of genes to a new location

• Transposable elements may also create newsites for alternative splicing in an RNAtranscript

• In all cases, changes are usually detrimentalbut may on occasion prove advantageous toan organism


Concept 21.6: Comparing genome sequencesprovides clues to evolution and development

• Genome sequencing has advanced rapidly inthe last 20 years

• Comparative studies of genomes

– Advance our understanding of the evolutionaryhistory of life

– Help explain how the evolution of developmentleads to morphological diversity

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Comparing Genomes

• Genome comparisons of closely relatedspecies help us understand recent evolutionaryevents

• Genome comparisons of distantly relatedspecies help us understand ancientevolutionary events

• Relationships among species can berepresented by a tree-shaped diagram

Fig. 21-15

Most recentcommonancestorof all livingthings

Billions of years ago4 3 2 1 0

Bacteria

Eukarya

Archaea

Chimpanzee

Human

Mouse

010203040506070Millions of years ago


Comparing Distantly Related Species

• Highly conserved genes are genes that havechanged very little over time

• These inform us about relationships amongspecies that diverged from each other a longtime ago

• Bacteria, archaea, and eukaryotes divergedfrom each other between 2 and 4 billion yearsago

• Highly conserved genes can be studied in onemodel organism, and the results applied toother organisms


Comparing Closely Related Species

• Genetic differences between closely relatedspecies can be correlated with phenotypicdifferences

• For example, genetic comparison of severalmammals with nonmammals helps identifywhat it takes to make a mammal


• Human and chimpanzee genomes differ by1.2%, at single base-pairs, and by 2.7%because of insertions and deletions

• Several genes are evolving faster in humansthan chimpanzees

• These include genes involved in defenseagainst malaria and tuberculosis, regulation ofbrain size, and genes that code fortranscription factors


• Humans and chimpanzees differ in theexpression of the FOXP2 gene whose productturns on genes involved in vocalization

• Differences in the FOXP2 gene may explainwhy humans but not chimpanzeescommunicate by speech

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Fig. 21-16

Wild type: two normalcopies of FOXP2

EXPERIMENT

RESULTS

Heterozygote: one copyof FOXP2 disrupted

Homozygote: both copiesof FOXP2 disrupted

Experiment 1: Researchers cut thin sections of brain and stainedthem with reagents, allowing visualization of brain anatomy in aUV fluorescence microscope.

Experiment 2: Researchers sepa-rated each newborn pup from itsmother and recorded the numberof ultrasonic whistles produced bythe pup.

Experiment 1 Experiment 2

Wild type Heterozygote Homozygote

Num

ber o

f whi

stle

s

Wildtype

Hetero-zygote

Homo-zygote

(Nowhistles)

0

100

200

300

400


Comparing Genomes Within a Species

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

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

• These variations are useful for studying humanevolution and human health


Comparing Developmental Processes

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

• Genomic information shows that minordifferences in gene sequence or regulation canresult in major differences in form


Widespread Conservation of Developmental GenesAmong Animals

• Molecular analysis of the homeotic genes inDrosophila has shown that they all include asequence called a homeobox

• An identical or very similar nucleotidesequence has been discovered in the homeoticgenes of both vertebrates and invertebrates

• Homeobox genes code for a domain thatallows a protein to bind to DNA and to functionas a transcription regulator

• Homeotic genes in animals are called Hoxgenes

Fig. 21-17

Adultfruit fly

Fruit fly embryo(10 hours)

Flychromosome

Mousechromosomes

Mouse embryo(12 days)

Adult mouse

Fig. 21-17a

Adultfruit fly

Fruit fly embryo(10 hours)

Flychromosome

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Fig. 21-17b

Mousechromosomes

Mouse embryo(12 days)

Adult mouse


• Related homeobox sequences have beenfound in regulatory genes of yeasts, plants,and even prokaryotes

• In addition to homeotic genes, many otherdevelopmental genes are highly conservedfrom species to species

Fig. 21-18

ThoraxGenitalsegments

Thorax Abdomen

Abdomen


• Sometimes small changes in regulatorysequences of certain genes lead to majorchanges in body form

• For example, variation in Hox gene expressioncontrols variation in leg-bearing segments ofcrustaceans and insects

• In other cases, genes with conservedsequences play different roles in differentspecies


Comparison of Animal and Plant Development

• In both plants and animals, development relieson a cascade of transcriptional regulatorsturning genes on or off in a finely tuned series

• Molecular evidence supports the separateevolution of developmental programs in plantsand animals

• Mads-box genes in plants are the regulatoryequivalent of Hox genes in animals

Fig. 21-UN1

Bacteria Archaea

Genomesize

Number of genes

Genedensity

Most are 1–6 Mb

1,500–7,500

Higher than in eukaryotes

Introns None inprotein-codinggenes

OthernoncodingDNA Very little

Present insome genes

Can be large amounts;generally more repetitivenoncoding DNA inmulticellular eukaryotes

Unicellular eukaryotes:present, but prevalent onlyin some speciesMulticellular eukaryotes:present in most genes

Lower than in prokaryotes(Within eukaryotes, lowerdensity is correlated with larger genomes.)

5,000–40,000

Most are 10–4,000 Mb, buta few are much larger

Eukarya

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You should now be able to:

1. Explain how linkage mapping, physicalmapping, and DNA sequencing eachcontributed to the Human Genome Project

2. Define and compare the fields of proteomicsand genomics

3. Describe the surprising findings of the HumanGenome Project with respect to the size of thehuman genome

4. Distinguish between transposons andretrotransposons


5. Explain how polyploidy may facilitate geneevolution

6. Describe in general terms the events that mayhave led to evolution of the globin superfamily

7. Explain the significance of the rapid evolutionof the FOXP2 gene in the human lineage

8. Provide evidence that suggests that thehomeobox DNA sequence evolved very earlyin the history of life

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