Transcript Chp 24 Lecture Outline

Genome Evolution
Chapter 24
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Introduction
• Genomes contain the raw material for
evolution
• Comparing whole genomes enhances
– Our ability to understand evolution
– To improve crops
– To identify genetic basis of disease
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Comparative Genomics
• Making the connection between a
specific change in a gene and a
modification in a morphological
character is difficult
• Genomes carry information on the
history of life
• Evolutionary differences accumulate
over long periods
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Comparative Genomics
• Genomes of viruses and bacteria
evolve in a matter of days
• Complex eukaryotic species
evolve over millions of years
• Example: tiger pufferfish (Fugu
rubripes), mouse (Mus musculus),
and human genomes
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Comparative Genomics
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Comparative Genomics
• Comparison between human and pufferfish
genomes
– Last shared common ancestor 450 MYA
– 25% human genes no counterparts in
Fugu
– Extensive genome rearrangements since
mammal lineage and teleost fish
diverged
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Comparative Genomics
– Human genome is 97% repetitive
DNA
– Repetitive DNA less than 1/6th Fugu
genome sequence
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Comparative Genomics
• Human and mouse genomes
– Human: 400 million more nucleotides
than the mouse
– 25,000 genes and they share 99%
– Diverged about 75 MYA
– 300 genes unique to either organism
(1%)
– Rearrangements of chromosomal
regions large and small
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Comparative Genomics
• Human and chimpanzee genomes
– Diverged 35 MYA
– 1.06% of the two genomes have fixed
differences in single nucleotides
– 1.5% difference in insertions and
deletions
– 53 of human-specific indels lead to lossof-function changes
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Comparative Genomics
– Smaller ratio in nonsynonymous to
synonymous changes
– Purifying selection: removal of
nonsynonymous genes
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Comparative Genomics
• Genomes evolve at different rates
• Mouse DNA has mutated twice as fast
as human
• Fruit fly and mosquito evolve more
rapidly than vertebrates
• Difference in generation time accounts
for different rates of genome evolution
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Comparative Genomics
• Plant, fungal, and animal genomes have
unique and shared genes
– Animal genomes are highly
conserved
– Plant genomes are highly conserved
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Comparative Genomics
• Comparison between two plant genomes
– Arabidopsis thaliana (mustard family
plant)
• 25,948 genes; 125 million base pairs
– Rice (Oryza sativa) 430 million base
pairs
– Share 80% of genes
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Comparative Genomics
Comparison of plants with animals and
fungi
– 1/3rd genes in Arabidopsis and rice
“plant” genes: distinguish plant
kingdom from animal kingdom
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Comparative Genomics
– Remaining genes similar to genes
found in animal and fungal genomes
• Basic intermediary metabolism
• Genome replication and repair
• RNA transcription & protein
synthesis
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Evolution of Whole Genomes
• Polyploidy can result from
– Genome duplication in one species
– Hybridization of two different species
• Autopolyploids: genome of one species
is duplicated through a meiotic error
– Four copies of each chromosome
• Allopolyploids: result from hybridization
and duplication of the genomes of two
different species
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Evolution of Whole Genomes
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Evolution of Whole Genomes
Evolutionary history of wheat
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Evolution of Whole Genomes
Ancient and newly created polyploids guide
studies of genome evolution
– Two avenues of research
• Paleopolyploids: comparisons of
polyploidy events
–Sequence divergence between
homologues
–Presence or absence of duplicated
gene pairs from hybridization
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Evolution of Whole Genomes
– Two avenues of research cont’d
• Synthetic polyploids: crossing
plants most closely related to
ancestral species and chemically
inducing chromosome doubling
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Evolution of Whole Genomes
• Plant polyploidy is ubiquitous, with
multiple common origins
• Comparison of soybean, forage legume,
and garden pea shows a huge
difference in genome size
• Some genomes increased, some
decreased in size
• Polyploidy induces elimination of
duplicated genes
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Evolution of Whole Genomes
Polyploidy has occurred numerous times
in the evolution of flowering plants
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Evolution of Whole Genomes
Genome downsizing
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Evolution of Whole Genomes
Polyploidy may be followed by the
unequal loss of duplicate genes from
the combined genomes
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Evolution of Whole Genomes
Transposons jump around following
polyploidization
– Barbara McClintock (Nobel Prize)
– Controlling elements: jumping DNA
regions
– Respond to genome shock and jump into
a new position
– New phenotypes could emerge
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Evolution of Whole Genomes
– New transposon insertions occur
because of unusually active
transposition
– New insertions could cause
• Gene mutations
• Changes in gene expression
• Chromosomal rearrangements
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Evolution Within Genomes
• Aneuploidy: duplication or loss of an
individual chromosome
• Plants are able to tolerate aneuploidy
better than animals
• Duplication of segments of DNA is one of
the greatest sources of novel traits
duplication
loss
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Evolution Within Genomes
• Fates of duplicate gene:
– Losing function through mutation
– Gaining a novel function through
mutation
– Having total function partitioned into
the two duplicates
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Evolution Within Genomes
Segmental duplication on the human Y
chromosome
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Evolution Within Genomes
• Gene duplication in humans is most likely to
occur in three most gene-rich chromosomes
– Growth and development genes
– Immune system genes
– Cell-surface receptor genes
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Evolution Within Genomes
• 5% of human genome consists of segmental
duplications
• Duplicated genes have different patterns of
gene expression
• Rates of duplication vary for different groups
of organisms
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Evolution Within Genomes
• Drosophila
– 31 new duplicates per genome per million
years (0.0023 duplications per gene per
million years)
– C. elegans 10 times fast rate
• Paralogues: two genes within an organism
that have arisen from duplication of a single
gene in an ancestor
• Orthologues: conservation of a single
gene from a common ancestor
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Evolution Within Genomes
Genome reorganization
• Humans have 1 fewer chromosome than
chimpanzees, gorillas, and orangutans
• Fusion of two genes into one gene;
chromosome 2 in humans
• Chromosomal rearrangements in mouse
ancestors have occurred at twice the rate
seen in humans
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Evolution Within Genomes
Chromosomal rearrangement
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Evolution Within Genomes
Variation in genomes
• Conservation of synteny: the preservation
over evolutionary time of arrangements of
DNA segments in related species
– Long segments of chromosomes in mice
and humans are the same
– Allows researchers to locate a gene in a
different species using information about
synteny
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Evolution Within Genomes
Soybean
d2
K
c2
b2
c1
3
2
M. truncatula
Synteny and gene identification
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Evolution Within Genomes
Gene inactivation results in pseudogenes
• Loss of gene function: way for genomes to
evolve
– Olfactory receptor (OR) genes:
inactivation best explanation for our
reduced sense of smell
– Primate genomes: > 1000 copies of OR
genes
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Evolution Within Genomes
• Pseudogenes: sequences of DNA that are
similar to functional genes but do not
function
– 70% of human OR genes are inactive
pseudogenes
– >50% gorilla & chimpanzee OR genes
function
– >95% New World monkey OR genes
work well
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Evolution Within Genomes
Active genes Pseudogenes
Nonolfactory DNA
Human olfactory
gene cluster
(chromosome 17)
Chimpanzee olfactory
gene cluster
(chromosome 19)
Gene inactivation
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Evolution Within Genomes
• Chimp genome analysis
– Indicated both humans and chimps are
gradually losing OR genes to
pseudogenes
– No evidence for positive selection for any
OR genes in chimps
• Vertical gene transfer (VGT): genes are
passed from generation to generation
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Evolution Within Genomes
• Horizontal gene transfer (HGT): genes
hitchhike from other species
– Can lead to phylogenetic complexity
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Evolution Within Genomes
• HGT continues today
• Phylogenies build with rRNA
sequences: Archaea more closely
related to Eukarya than to Bacteria
• Organisms swapped genes
• Find organisms with both Archaea and
Bacteria genes
• Perhaps tree of life is more of a web
than a branch
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Evolution Within Genomes
Phylogeny based on a universal common
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ancestor
Evolution Within Genomes
• Contribution to the evolution of
genomes
– Segmental duplication
– Genome rearrangement
– Loss of gene function
• HGT leads to mixing of genes among
organisms
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Gene Function and Expression
Patterns
• Inferred by comparing genes in different
species
• Why a mouse develops into a mouse and
not a human
– Genes are expressed at different times
– In different tissues
– In different amounts
– In different combinations
– Example: cystic fibrosis gene
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Gene Patterns
• Chimp DNA: 98.7% identical to human
• Chimp protein genes: 99.2% identical
• Experiment: human and chimp brain cells
– Patterns of gene transcription activity
differed
– Same genes transcribed
• Patterns and levels of transcription
varied
• Posttranscriptional differences
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Gene Expression
• Speech
– FOXP2 gene: single point mutation =
impaired speech and grammar but not
language comprehension
– FOXP2 found in chimps, gorillas,
orangutans, rhesus macaques, and mice
– FOXP2 protein in mice and humans differs
by only 3 AA, 2 AA in other primates
• Gene expressed in areas of brain that
affect motor function
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Gene Expression
• The difference of only 2 AA sequences for
FOXP2 appears to have made it possible for
language to arise
– Selective pressure for the 2 FOXP2
mutations
– Allow brain, larynx and mouth to
coordinate to produce speech
– Linked to signaling and gene expression
– FOXP2 mutation in mice-no squeak !
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Gene Pattern and Expression
• Diverse life forms emerge from similar
toolkits of genes
• To understand functional difference:
– Look at time and place of expression
• Small changes in a protein can affect
gene function
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Nonprotein-coding DNA
• Repetitive DNA 30% of animal; 40-80% of
plant genomes
• Mice & human repetitive DNA similar
– Retrotransposon DNA in both species:
independently ended up in comparable
regions
– May not be “junk” DNA
– A single retrotransposon mutation can
cause heritable differences in coat color in
mice
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Genome Size and Gene
Number
• Genome size has varied over evolutionary
time
• Increases or decreases in size do not
correlate with number of genes
• Polyploidy in plants does not by itself
explain differences in genome size
• A greater amount of DNA is explained by the
presence of introns and nonprotein-coding
sequences than gene duplicates
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Disease
• Sequences conserved between humans
and pufferfish provide clues for
understanding the genetic basis of human
disease
• Amino acids:
– Critical to protein function are preserved
– Changes more likely to cause disease
• Pufferfish genome  conserved
sequences in humans
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Disease
• Closely related organisms enhance medical
research
– Use mouse and rat genome to compare
to human
– Use mice and rats to detect disease from
genetic mutations
• Aid medical research in developing
treatments for human diseases
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Disease
• Pathogen-host genome differences
reveal drug targets
– Malaria: Human disease caused by
a protist with the mosquito as a
vector
– ~ 2.5 million deaths/year
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Disease
– Plasmodium falciparum:
5300 genes
• Hides in RBCs
• Subcellular component
called apicoplast
• 12% of protein encoded
go to apicoplast
• Makes fatty acids: target
apicoplast and possibly
kill the parasite
apicoplast
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Disease
• Chagas Disease
– Trypanasoma cruzi: insect borne
protozoan
– Kills ~ 21,000 people/ year with 18 million
suffering from infection
– Genome sequencing completed in 2005
– Common core of 6200 genes shared
among the three pathogens T. cruzi,
Leishmania major, T. brucei.
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Disease
Comparative genomics may aid in drug
development
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Crop Improvement
• Model plant genomes provide links to
genetics of crop plants
• Beneficial bacterial genes can be located
and utilized
– Pseudomonas fluorescens naturally
protects plant roots from disease
– Work on identifying chemical pathways
– Understanding pathways = more effective
methods of crop protection
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