Genome Evolution

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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
  loss-of-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 contd
• 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 gt 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
• gt50 gorilla chimpanzee OR genes function
• gt95 New World monkey OR genes work well

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Evolution Within Genomes
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 ancestor

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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