Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Figure 21.1 Chapter 21...

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Figure 21.1

Chapter 21

Genomes and their Evolution


Overview: Reading the Leaves from the Tree of Life

• Genome sequences exist human, chimpanzee, E. coli, brewer’s yeast, corn, fruit fly, house mouse, rhesus macaque, ……….

• Provides information about the evolutionary history of genes and taxonomic groups

© 2011 Pearson Education, Inc.


• Genomics is the study of whole sets of genes and their interactions

• Bioinformatics is the application of computational methods to the storage and analysis of biological data



Genome Sequencing

• Human Genome Project began in 1990 largely completed by 2003

• 3 stages

– Genetic (or linkage) mapping

– Physical mapping

– DNA sequencing



• Linkage Mapping maps location of several thousand genetic markers on each chromosome

• genetic marker gene or other identifiable DNA sequence

• Recombination frequencies used to determine the order & relative distances between genetic markers



Figure 21.2-1

Cytogenetic map

Genes locatedby FISH

Chromosomebands


Figure 21.2-2

Cytogenetic map


Chromosomebands

Linkage mapping

Geneticmarkers

1


Figure 21.2-3

Cytogenetic map


Chromosomebands

Linkage mapping

Geneticmarkers

1

Physical mapping2

Overlappingfragments


Figure 21.2-4

Cytogenetic map


Chromosomebands

Linkage mapping

Geneticmarkers

1

Physical mapping2

Overlappingfragments

DNA sequencing3


• Physical Map distance between genetic markers, (number of bp)

• Constructed by cutting DNA molecule into short fragments and arranging them in order by identifying overlaps



• Sequencing determines the complete nucleotide sequence of each chromosome

• Human genome = 3.2 billion bp



Whole-Genome Shotgun Approach to Genome Sequencing

• Developed by J. Craig Venter (1992)

• Skips genetic and physical mapping and sequences random DNA fragments directly

• Powerful computer programs are used to order fragments



Cut the DNA intooverlapping frag-ments short enoughfor sequencing.

1

Clone the fragmentsin plasmid or phagevectors.

2

Figure 21.3-1



1


2

Sequence eachfragment.

3

Figure 21.3-2



1


2

Sequence eachfragment.

3

Order thesequences intoone overallsequencewith computersoftware.

4

Figure 21.3-3


• 3-stage process and shotgun used for the Human Genome Project and for genome sequencing of other organisms

• Newer sequencing techniques massive increases in speed and decreases in cost

$3,000,000,000.00 $1,000.00



• Metagenomics environmental sample is sequenced

• Eliminates need to culture species in the lab



Using bioinformatics to analyze genomes and their functions

• The Human Genome Project has accelerated progress in DNA sequence analysis



Centralized Resources for Analyzing Genome Sequences

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

– BGI in Shenzhen, China

– 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 to search 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 all protein structures that have been determined



Figure 21.4


• Identification of protein coding genes within DNA sequences in a database is called gene annotation

• Comparison of unknown genes to known genes in other species provides clues about function



• Proteomics systematic study of all proteins encoded by a genome



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

Figure 21.5

Systems biology approach define gene circuits and protein interaction networks


Figure 21.5a

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


biosynthesis

Peroxisomalfunctions


Glutamatebiosynthesis

Serine-related

biosynthesis

Amino acidpermease pathway

Vesiclefusion


biosynthesis

Figure 21.5b


Systems Biology in Medicine

– The Cancer Genome Atlas project is currently seeking all the common mutations in three types of cancer by comparing gene sequences and expression in cancer versus normal cells

– Silicon and glass “chips” have been produced that hold a microarray of most known human genes



Figure 21.6


Genomes

• By early 2010, 1,200 genomes were completely sequenced, including 1,000 bacteria, 80 archaea, and 124 eukaryotes

• Sequencing of over 5,500 genomes and over 200 metagenomes is currently in progress



Genome Size

• Bacteria and archaea 1 to 6 million base pairs (Mb)

• Plant & animal greater than 100 Mb; humans 3,000 Mb

• Within each domain there is no systematic relationship between genome size and phenotype



Table 21.1


Number of Genes

• Bacteria and archaea have 1,500 to 7,500 genes

• Eukaryotes from 40,000 genes



• Number of genes is not correlated to genome size

• Vertebrate genomes can produce more than one polypeptide per gene because of alternative splicing of RNA transcripts



Multicellular eukaryotes have much noncoding DNA and many multigene families

• Previously called “junk DNA” plays important roles in the cell



• Sequencing of the human genome reveals that 98.5% does not code for proteins, rRNAs, or tRNAs



• About 25% of the human genome introns and gene-related regulatory sequences (5%)

• Intergenic DNA is noncoding DNA found between genes

– Pseudogenes are former genes that have accumulated mutations and are nonfunctional

– Repetitive DNA is present in multiple copies in the genome



• About three-fourths of repetitive DNA is made up of transposable elements



Figure 21.7Exons (1.5%) Introns (5%)

Regulatorysequences(20%)

UniquenoncodingDNA (15%)

RepetitiveDNA unrelated totransposableelements(14%)

Large-segmentduplications (56%)

Simple sequenceDNA (3%)

Alu elements(10%)

L1sequences(17%)

RepetitiveDNA thatincludestransposableelementsand relatedsequences(44%)


Transposable Elements

• First evidence came from geneticist Barbara McClintock’s breeding experiments with Indian corn

• Identified changes in the color of kernels that made sense only by mobile genetic elements

• Present in both prokaryotes and eukaryotes



Figure 21.8


Figure 21.9

Transposon

Transposonis copied

DNA ofgenome

Mobile transposon

Insertion

New copy oftransposon


Figure 21.10

RetrotransposonNew copy of

retrotransposon

Insertion

Reversetranscriptase

RNA

Formation of asingle-stranded

RNA intermediate


Sequences Related to Transposable Elements

• In primates, a large portion are a family called Alu elements

• Function, if any, is unknown



Other Repetitive DNA, Including Simple Sequence DNA

• Many copies of tandemly repeated short sequences

• Series of repeating units of 2 to 5 nucleotides is called a short tandem repeat (STR)



Genes and Multigene Families

• Collections of identical or very similar genes



Figure 21.11

DNARNA transcripts

Nontranscribedspacer Transcription unit

DNA

18S 5.8S 28S

28S5.8S

18S

(a) Part of the ribosomal RNA gene family

-Globin

-Globin gene family

Chromosome 16

-Globin gene family

Chromosome 11

-Globin

Heme

21

21

G A

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

EmbryoFetus

and adult Fetus Adult

rRNA

Embryo


Duplication, rearrangement, and mutation of DNA contribute to genome evolution

• Earliest forms of life minimal number of genes, (only those necessary for survival and reproduction)

• Size of genomes has increased over evolutionary time, (extra genetic material raw material for gene diversification)



Alterations of Chromosome Structure

• Humans have 23 pairs of chromosomes, while chimpanzees have 24 pairs

• 2 ancestral chromosomes fused in the human line



Figure 21.12

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


Evolution of Genes with Related Functions: The Human Globin Genes

• Globin genes evolved from common ancestral globin gene, which duplicated and diverged about 450–500 mya

• Differences arose from accumulation of mutations



Figure 21.14

Ancestral globin gene

-Globin gene familyon chromosome 16

-Globin gene familyon chromosome 11

Duplication ofancestral gene

Mutation inboth copies

Transposition todifferent chromosomes

Further duplicationsand mutations

Evo

luti

on

ary

tim

e

2

1

2 1 G A


Evolution of Genes with Novel Functions

• Some duplicated genes have diverged so much that the functions of encoded proteins are now very different

• e.g. lysozyme gene was duplicated and evolved into the gene that encodes α-lactalbumin in mammals (milk production role)



Rearrangements of Parts of Genes: Exon Duplication and Exon Shuffling

• Has contributed to genome evolution

• Mixing and matching of exons



Exonduplication

Exonshuffling

Exonshuffling

F EGF K K

K

F F F F

EGF EGF EGF EGF

Epidermal 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

Figure 21.15


How Transposable Elements Contribute to Genome Evolution

• Multiple copies of similar transposable elements may facilitate recombination, or crossing over, between different chromosomes

• Insertion of transposable elements within a protein-coding sequence may block protein production

• Insertion of transposable elements within a regulatory sequence may increase or decrease protein production



• Transposable elements may carry a gene or groups of genes to a new position

• Transposable elements may also create new sites for alternative splicing in an RNA transcript

• In all cases, changes are usually detrimental but may on occasion prove advantageous



Comparing genome sequences provides clues to evolution and development

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

• Genome comparisons of distantly related species help us understand ancient evolutionary events

• Relationships among species can be represented by a tree-shaped diagram



Most recentcommonancestorof all livingthings

Bacteria

Eukarya

Archaea

Chimpanzee

Human

Mouse

Millions of years ago

Billions of years ago4 3 2

010203040506070

01

Figure 21.16


Comparing Distantly Related Species

• Highly conserved genes have changed very little over time

• Clarify relationships among species

• Bacteria, archaea, and eukaryotes diverged from each other between 2 and 4 billion years ago

• Results from model organisms applied to other organisms



Comparing Closely Related Species

• Human and chimpanzee genomes differ by 1.2%, at single base-pairs, and by 2.7% because of insertions and deletions

• Several genes are evolving faster in humans than chimpanzees

• These include genes involved in defense against malaria and tuberculosis, regulation of brain size, and genes that code for transcription factors



• Humans and chimpanzees differ in the expression of the FOXP2 gene, (vocalization gene)

• May explain why humans but not chimpanzees communicate by speech



Comparing Genomes Within a Species

• Human species only 200,000 years old low within-species genetic variation

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

• Variations useful for studying human evolution and human health



Comparing Developmental Processes

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

• Minor differences in gene sequence or regulation can result in striking differences in form



Widespread Conservation of Developmental Genes Among Animals

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

• An identical or very similar nucleotide sequence has been discovered in the homeotic genes of both vertebrates and invertebrates

• Homeobox genes code for a domain that allows a protein to bind to DNA and to function as a transcription regulator

• Homeotic genes in animals are called Hox genes© 2011 Pearson Education, Inc.


Figure 21.18

Adultfruit fly

Fruit fly embryo(10 hours)

Fly chromosome

Mousechromosomes

Mouse embryo(12 days)

Adult mouse


Figure 21.18a

Adultfruit fly

Fruit fly embryo(10 hours)

Fly chromosome


Figure 21.18b

Mousechromosomes

Mouse embryo(12 days)

Adult mouse


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

• In addition to homeotic genes, many other developmental genes are highly conserved from species to species



• Sometimes small changes in regulatory sequences of certain genes lead to major changes in body form

• For example, variation in Hox gene expression controls variation in leg-bearing segments of crustaceans and insects

• In other cases, genes with conserved sequences play different roles in different species



Figure 21.19

Thorax AbdomenGenitalsegments

Thorax Abdomen


Comparison of Animal and Plant Development

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

• Molecular evidence supports the separate evolution of developmental programs in plants and animals

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



Archaea

Most are 16 Mb

Eukarya

Genomesize

Number ofgenes

Genedensity

Introns

OthernoncodingDNA Very little

None inprotein-codinggenes

Present insome genes

Higher than in eukaryotes

1,5007,500 5,00040,000

Most are 104,000 Mb, but a few are much larger

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

Unicellular eukaryotes:present, but prevalent only insome speciesMulticellular eukaryotes:present in most genes

Can be large amounts;generally more repetitivenoncoding DNA inmulticellular eukaryotes

Bacteria

Figure 21.UN01


Protein-coding,rRNA, and

tRNA genes (1.5%)

Human genome

Introns andregulatory

sequences (26%)

Repetitive DNA(green and teal)

Figure 21.UN02


Figure 21.UN03

-Globin gene family

Chromosome 16

-Globin gene family

Chromosome 11

2

12 1 G A


Figure 21.UN04


Figure 21.UN05

Crossoverpoint


Figure 21.UN06

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