Evolution by Genome Duplication

1
Evolution by Genome Duplication
http//news.bbc.co.uk/1/hi/sci/tech/222591.stm
Itai Yanai Department of Biology Technion
Israel Institute of Technology
2
Evolution by Genome Duplication
Susumu Ohno and evolution by gene duplication The
Drosophila genome Homeotic mutations Hox
genes What is an animal? Genome Duplication
during chordate evolution Genome duplications
happen(ed) The 2R hypothesis Methods of molecular
archeology Map-based (spatial) S. cerevisiae
and Arabidopsis examples Tree-based
(temporal) Recent progress suggests one genome
duplication in vertebrate evolution.
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The standard model of genome evolution
DNA sequence
Mutations
The engine
DRIFT
SELECTION (purifying or positive)
The steering wheel
DNA sequence (Altered)
4
Metazoan phylogeny
800-1000 Mya
Carroll S.B. et al. From DNA to Diversity (2001)
Blackwell Science
5
What is the birth of creativity, novelty,
diversity?
Or, how do you acquire new function while
maintaining the old?
Carroll S.B. et al. From DNA to Diversity (2001)
Blackwell Science
6
GATCTACCATGAAAGACTTGTGAATCCAGGAAGAGAGACTGACTGGGCAA
CATGTTATTCAGGTACAAAAAGATTTGGACTGTAACTTAAAAATGATCAA
ATTATGTTTCCCATGCATCAGGTGCAATGGGAAGCTCTTCTGGAGAGTGA
GAGAAGCTTCCAGTTAAGGTGACATTGAAGCCAAGTCCTGAAAGATGAGG
AAGAGTTGTATGAGAGTGGGGAGGGAAGGGGGAGGTGGAGGGATGGGGAA
TGGGCCGGGATGGGATAGCGCAAACTGCCCGGGAAGGGAAACCAGCACTG
TACAGACCTGAACAACGAAGATGGCATATTTTGTTCAGGGAATGGTGAAT
TAAGTGTGGCAGGAATGCTTTGTAGACACAGTAATTTGCTTGTATGGAAT
TTTGCCTGAGAGACCTCATTGCAGTTTCTGATTTTTTGATGTCTTCATCC
ATCACTGTCCTTGTCAAATAGTTTGGAACAGGTATAATGATCACAATAAC
CCCAAGCATAATATTTCGTTAATTCTCACAGAATCACATATAGGTGCCAC
AGTTATCCCCATTTTATGAATGGAGTEvolutionbyDuplicationGA
TGAAAACCTTAGGAATAATGAATGATTTGCGCAGGCTCACCTGGATATTA
AGACTGAGTCAAATGTTGGGTCTGGTCTGACTTTAATGTTTGCTTTGTTC
ATGAGCACCACATATTGCCTCTCCTATGCAGTTAAGCAGGTAGGTGACAG
AAAAGCCCATGTTTGTCTCTACTCACACACTTCCGACTGAATGTATGTAT
GGAGTTTCTACACCAGATTCTTCAGTGCTCTGGATATTAACTGGGTATCC
CATGACTTTATTCTGACACTACCTGGACCTTGTCAAATAGTTTGGACCTT
GTCAAATAGTTTGGAGTCCTTGTCAAATAGTTTGGGGTTAGCACAGACCC
CACAAGTTAGGGGCTCAGTCCCACGAGGCCATCCTCACTTCAGATGACAA
TGGCAAGTCCTAAGTTGTCACCATACTTTTGACCAACCTGTTACCAATCG
GGGGTTCCCGTAACTGTCTTCTTGGGTTTAATAATTTGCTAGAACAGTTT
ACGGAACTCAGAAAAACAGTTTATTTTCTTTTTTTCTGAGAGAGAGGGTC
TTATTTTGTTGCCCAGGCTGGTGTGCAATGGTGCAGTCATAGCTCATTGC
AGCCTTGATTGTCTGGGTTCCAGTGGTTCTCCCACCTCAGCCTCCCTAGT
AGCTGAGACTACATGCCTGCACCACCACATCTGGCTAGTTTCTTTTATTT
TTTGTATAGATGGGGTCTTGTTGTGTTGGCCAGGCTGGCCACAAATTCCT
GGTCTCAAGTGATCCTCCCACCTCAGCCTCTGAAAGTGCTGGGATTACAG
ATGTGAGCCACCACATCTGGCCAGTTCATTTCCTATTACTGGTTCATTGT
GAAGGATACATCTCAGAAACAGTCAATGAAAGAGACGTGCATGCTGGATG
CAGTGGCTCATGCCTGTAATCTCAGCACTTTGGGAGGCCAAGGTGGGAGG
ATCGCTTAAACTCAGGAGTTTGAGACCAGCCTGGGCAACATGGTGAAAAC
CTGTCTCTATAAAAAATTAAAAAATAATAATAATAACTGGTGTGGTGTTG
TGCACCTAGAGTTCCAACTACTAGGGAAGCTGAGATGAGAGGATACCTTG
AGCTGGGGACTGGGGAGGCTTAGGTTACAGTAAGCTGAGATTGTGCCACT
GCACTCCAGCTTGGACAAAAGAGCCTGATCCTGTCTCAAAAAAAAGAAAG
ATACCCAGGGTCCACAGGCACAGCTCCATCGTTACAATGGCCTCTTTAGA
CCCAGCTCCTGCCTCCCAGCCTTCT
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Evolution by Gene Duplication Susumu Ohno, 1970
natural selection merely modified, while
redundancy created
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It is said that necessity is the mother of
invention. To be sure, wheels and pulleys were
invented out of necessity by the tenacious minds
of upright citizens. Looking at the history of
mankind, however, one has to add that leisure is
the mother of cultural improvement. Mans
creative genius flourished only when his mind,
freed, from the worry of daily toils, was
permitted to entertain apparently useless
thoughts.   In the same manner, one might say
with regard to evolution that natural selection
merely modified, while redundancy created.
Natural selection has been extremely effective in
policing allelic mutations which arise in already
existing gene loci. Because of natural selection,
organisms have been able to adapt to changing
environments, and by adaptive radiation many new
species were created from a common ancestral
form. Yet, being an effective policeman, natural
selection is extremely conservative by nature.
Had evolution been entirely dependent upon
natural selection, from a bacterium only numerous
forms of bacteria would have emerged. The
creation of metazoans, vertebrates and finally
mammals from unicellular organisms would have
been quite impossible, for such big leaps in
evolution required the creation of new gene loci
with previously nonexistent functions. Only the
cistron which became redundant was able to escape
from the relentless pressure of natural
selection, and by escaping, it accumulated
formerly forbidden mutations to emerge as a new
gene locus.
-         Susumu Ohno, Evolution by Gene
Duplication (1970)
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A new function is created by duplicating an old
gene and modifying the copy.
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Duplications occur at all genomic scales!
Short indels
Apparent Frequency
Domain (exon)
Gene
Gene cluster
Segment
Chromosome
Genome
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A modified model of genome evolution
DNA sequence
Single nucleotide changes, short insertions or
deletions, inversions, recombinations, domain
duplication, gene duplication, cluster
duplication, segment duplication, chromosome
duplication, genome duplication,
DRIFT
SELECTION (purifying or positive)
Mutations of different kinds
The steering wheel
DNA sequence (Altered)
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GATCTACCATGAAAGACTTGTGAATCCAGGAAGAGAGACTGACTGGGCAA
CATGTTATTCAGGTACAAAAAGATTTGGACTGTAACTTAAAAATGATCAA
ATTATGTTTCCCATGCATCAGGTGCAATGGGAAGCTCTTCTGGAGAGTGA
GAGAAGCTTCCAGTTAAGGTGACATTGAAGCCAAGTCCTGAAAGATGAGG
AAGAGTTGTATGAGAGTGGGGAGGGAAGGGGGAGGTGGAGGGATGGGGAA
TGGGCCGGGATGGGATAGCGCAAACTGCCCGGGAAGGGAAACCAGCACTG
TACAGACCTGAACAACGAAGATGGCATATTTTGTTCAGGGAATGGTGAAT
TAAGTGTGGCAGGAATGCTTTGTAGACACAGTAATTTGCTTGTATGGAAT
TTTGCCTGAGAGACCTCATTGCAGTTTCTGATTTTTTGATGTCTTCATCC
ATCACTGTCCTTGTCAAATAGTTTGGAACAGGTATAATGATCACAATAAC
CCCAAGCATAATATTTCGTTAATTCTCACAGAATCACATATAGGTGCCAC
AGTTATCCCCATTTTATGAATGGAGGATGAAAACCTTAGGAATAATGAAT
GATTTGCGCAGGCTCACCTGGATATTAAGACTGAGTCAAATGTTGGGTCT
GGTCTGACTTTAATGTTTGCTTTGTTCATGAGCACCACATATTGCCTCTC
CTATGCAGTTAAGCAGGTAGGTGACAGAAAAGCCCATGTTTGTCTCTACT
CACACACTTCCGACTGAATGTATGTATGGAGTTTCTACACCAGATTCTTC
AGTGCTCTGGATATTAACTGGGTATCCCATGACTTTATTCTGACACTACC
TGGACCTTGTCAAATAGTTTGGACCTTGTCAAATAGTTTGGAGTCCTTGT
CAAATAGTTTGGGGTTAGCACAGACCCCACAAGTTAGGGGCTCAGTCCCA
CGAGGCCATCCTCACTTCAGATGACAATGGCAAGTCCTAAGTTGTCACCA
TACTTTTGACCAACCTGTTACCAATCGGGGGTTCCCGTAACTGTCTTCTT
GGGTTTAATAATTTGCTAGAACAGTTTACGGAACTCAGAAAAACAGTTTA
TTTTCTTTTTTTCTGAGAGAGAGGGTCTTATTTTGTTGCCCAGGCTGGTG
TGCAATGGTGCAGTCATAGCTCATTGCAGCCTTGATTGTCTGGGTTCCAG
TGGTTCTCCCACCTCAGCCTCCCTAGTAGCTGAGACTACATGCCTGCACC
ACCACATCTGGCTAGTTTCTTTTATTTTTTGTATAGATGGGGTCTTGTTG
TGTTGGCCAGGCTGGCCACAAATTCCTGGTCTCAAGTGATCCTCCCACCT
CAGCCTCTGAAAGTGCTGGGATTACAGATGTGAGCCACCACATCTGGCCA
GTTCATTTCCTATTACTGGTTCATTGTGAAGGATACATCTCAGAAACAGT
CAATGAAAGAGACGTGCATGCTGGATGCAGTGGCTCATGCCTGTAATCTC
AGCACTTTGGGAGGCCAAGGTGGGAGGATCGCTTAAACTCAGGAGTTTGA
GACCAGCCTGGGCAACATGGTGAAAACCTGTCTCTATAAAAAATTAAAAA
ATAATAATAATAACTGGTGTGGTGTTGTGCACCTAGAGTTCCAACTACTA
GGGAAGCTGAGATGAGAGGATACCTTGAGCTGGGGACTGGGGAGGCTTAG
GTTACAGTAAGCTGAGATTGTGCCACTGCACTCCAGCTTGGACAAAAGAG
CCTGATCCTGTCTCAAAAAAAAGAAAGATACCCAGGGTCCACAGGCACAG
CTCCATCGTTACAATGGCCTCTTTAGACCCAGCTCCTGCCTCCCAGCCTT
CT
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The Drosophila genome
120-megabase euchromatic portion was sequenced
euchromatic true chromatin non
repetitive genome regions
Adams, M.D. et al. Science 2000 287 2185-2195
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Drosophila has gt13,000 genes
Misra et al. Genome Biology 2002
3(12)research0083.1-0083.22
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Drosophila homeobox genes as example of gene
duplication
Homeotic mutants
Normal fly
Extra set of wings! Ubx (Ultrabithorax) gene
mutant
Antennae are transformed into legs! Antp
(Antennapedia) gene mutant
Carroll S.B. et al. From DNA to Diversity (2001)
Blackwell Science
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Eight homeobox (Hox) genes regulate the identity
of regions within the adult and embryo.
Adult
Embryo
Carroll S.B. et al. From DNA to Diversity (2001)
Blackwell Science
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The Hox genes are paralogs with a highly
conserved homeobox domain
Multiple alignment of the homeobox domain
The Hox genes are transcription regulators and
the Homeobox domain is DNA-binding domain.
Carroll S.B. et al. From DNA to Diversity (2001)
Blackwell Science
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Vertebrates have 4 Hox clusters
Human chromosomes
Carroll S.B. et al. From DNA to Diversity (2001)
Blackwell Science
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Evolution of Metazoan Hox genes
Carroll S.B. et al. From DNA to Diversity (2001)
Blackwell Science
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What is an animal?
From the book of Bunny Suicides
Textbook definition an organism that feeds,
moves and responds to stimuli.
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The phylotypic stage
Haeckel's 1874 version of vertebrate embryonic
development.
The top row shows an early stage common to all
groups, the second row shows a middle stage of
development, and the bottom row shows a late
stage embryo.
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An animal is an organism that displays a
particular spatial pattern of gene expression
(zootype)
The zootype defines the spatial order of anterior
expression limits of the Hox cluster and some
other genes.
Slack et al. Nature 361 (1993), 490-492
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Origin of the zootype on the evolutionary tree
Slack et al. Nature 361 (1993), 490-492
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GATCTACCATGAAAGACTTGTGAATCCAGGAAGAGAGACTGACTGGGCAA
CATGTTATTCAGGTACAAAAAGATTTGGACTGTAACTTAAAAATGATCAA
ATTATGTTTCCCATGCATCAGGTGCAATGGGAAGCTCTTCTGGAGAGTGA
GAGAAGCTTCCAGTTAAGGTGACATTGAAGCCAAGTCCTGAAAGATGAGG
AAGAGTTGTATGAGAGTGGGGAGGGAAGGGGGAGGTGGAGGGATGGGGAA
TGGGCCGGGATGGGATAGCGCAAACTGCCCGGGAAGGGAAACCAGCACTG
TACAGACCTGAACAACGAAGATGGCATATTTTGTTCAGGGAATGGTGAAT
TAAGTGTGGCAGGAATGCTTTGTAGACACAGTAATTTGCTTGTATGGAAT
TTTGCCTGAGAGACCTCATTGCAGTTTCTGATTTTTTGATGTCTTCATCC
ATCACTGTCCTTGTCAAATAGTTTGGAACAGGTATAATGATCACAATAAC
CCCAAGCATAATATTTCGTTAATTCTCACAGAATCACATATAGGTGCCAC
AGTTATCCCCATTTTATGAATGGAGTEvolutionbyGenomeDuplica
tionGATGAAAACCTTAGGAATAATGAATGATTTGCGCAGGCTCACCTGG
ATATTAAGACTGAGTCAAATGTTGGGTCTGGTCTGACTTTAATGTTTGCT
TTGTTCATGAGCACCACATATTGCCTCTCCTATGCAGTTAAGCAGGTAGG
TGACAGAAAAGCCCATGTTTGTCTCTACTCACACACTTCCGACTGAATGT
ATGTATGGAGTTTCTACACCAGATTCTTCAGTGCTCTGGATATTAACTGG
GTATCCCATGACTTTATTCTGACACTACCTGGACCTTGTCAAATAGTTTG
GACCTTGTCAAATAGTTTGGAGTCCTTGTCAAATAGTTTGGGGTTAGCAC
AGACCCCACAAGTTAGGGGCTCAGTCCCACGAGGCCATCCTCACTTCAGA
TGACAATGGCAAGTCCTAAGTTGTCACCATACTTTTGACCAACCTGTTAC
CAATCGGGGGTTCCCGTAACTGTCTTCTTGGGTTTAATAATTTGCTAGAA
CAGTTTACGGAACTCAGAAAAACAGTTTATTTTCTTTTTTTCTGAGAGAG
AGGGTCTTATTTTGTTGCCCAGGCTGGTGTGCAATGGTGCAGTCATAGCT
CATTGCAGCCTTGATTGTCTGGGTTCCAGTGGTTCTCCCACCTCAGCCTC
CCTAGTAGCTGAGACTACATGCCTGCACCACCACATCTGGCTAGTTTCTT
TTATTTTTTGTATAGATGGGGTCTTGTTGTGTTGGCCAGGCTGGCCACAA
ATTCCTGGTCTCAAGTGATCCTCCCACCTCAGCCTCTGAAAGTGCTGGGA
TTACAGATGTGAGCCACCACATCTGGCCAGTTCATTTCCTATTACTGGTT
CATTGTGAAGGATACATCTCAGAAACAGTCAATGAAAGAGACGTGCATGC
TGGATGCAGTGGCTCATGCCTGTAATCTCAGCACTTTGGGAGGCCAAGGT
GGGAGGATCGCTTAAACTCAGGAGTTTGAGACCAGCCTGGGCAACATGGT
GAAAACCTGTCTCTATAAAAAATTAAAAAATAATAATAATAACTGGTGTG
GTGTTGTGCACCTAGAGTTCCAACTACTAGGGAAGCTGAGATGAGAGGAT
ACCTTGAGCTGGGGACTGGGGAGGCTTAGGTTACAGTAAGCTGAGATTGT
GCCACTGCACTCCAGCTTGGACAAAAGAGCCTGATCCTGTCTCAAAAAAA
AGAAAGATACCCAGGGTCCACAGGCACAGCTCCATCGTTACAATGGCCTC
TTTAGACCCAGCTCCTGCCTCCCAGCCTTCT
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Susumu Ohno and the 2R hypothesis
It is our contention that the ancestors of
reptiles, birds, and mammals have experienced at
least one tetraploid evolution either at the
stage of fish or at the stage of amphibians
(1970) A mammalian ancestor might have gone
through at least one round of tetraploid
evolution at the stage of fish (1973)
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Distribution of chromosome number in fishes is
bi-modal
Evolution by gene duplication, Ohno (1970)
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At least 7 Hox clusters in zebrafish
Amores et al. (1998) Science 282 1711-1714
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Problems genome duplication solves

• Dosage relationship of functionally related genes
• Each structural gene is accompanied by
  duplication of its own regulator
• Much more on evolution of gene function in the
  next lecture...

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Evidence 1 Large segments of conserved synteny
are indeed present
Synthenic regions of human chromosome 11 on
other human chromsomes
Science v. 291, pp 1304-1351
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Evidence 2 Vertebrates have 4 copies of the Hox
cluster
Carroll S.B. et al. From DNA to Diversity (2001)
Blackwell Science
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Detected genome duplication events
genome duplication
Van de Peer et al. Nature Reviews Genetics (2009)
32
The one-to-four rule The human genome
contains up to four paralogs of many Drosophila
genes.
Spring J. FEBS Letters 400 (1997) 2-8
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Examples of the one-to-four rule
Spring J. Nature Genetics (2002) 31 128-129
34
Things Fall Apart, or
How to turn 5 genes into 9 by a 2R model
Wolfe, K.H. Nature Reviews Genetics (2001) 2
333-341
35
Methods for detecting genome duplications

• Spatial Map-based approach
• using knowledge of the order of genes along
  complete genomes
• Temporal Tree-based approach
• using the molecular clock to estimate the age of
  the duplication

Ken Wolfe Genome Duplication archaeologist par
excellence
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Map-based approach A systematic search for
duplicated regions in S. cerevisiae
3 separate diagonals indicate 3 distinct regional
duplications
Interspersed within the clusters are gene that
are not duplicated (result of regional
duplications)
Wolfe K.H. and Shields D.C. Nature (1997) 387
708-713
37
55 duplicate regions were identified

• 376 pairs of homologous genes
• Covering 50 of the genome

Wolfe K.H. and Shields D.C. Nature (1997) 387
708-713
38
How did these 55 duplicated regions arise?
By successive duplications
Simultaneously by a single duplication of the
entire genome (tetraploidy)
-OR-
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The duplicates are not duplicated again
Duplication
Duplication of duplicate
If duplications were successive, then about 7 of
the 55 duplications would be expected to be in
triplicated regions
Triplicated regions are not observed!
40
50 of the 55 duplicated regions conserve the
orientation with respect to the centromere.
Chrom. XVI
centromere
Chrom. VII
centromere
What does this signify?
Wolfe K.H. and Shields D.C. Nature (1997) 387
708-713
41
Reciprocal translocation
mutual exchange of segments between nonhomologous
chromosomes
http//www.ucl.ac.uk/ucbhjow/bmsi/bmsi_7.html
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S. cerevisiae is a paleoploid

• 100 million years ago, two ancestral diploid
  yeast cells each containing about 5000 genes
  fused to form a tetraploid.
• The species then became diploid (decay of
  sequence identity) and most (85) of the
  duplicate copies were deleted.
• Current species with a haploid diploid life cycle
  and 5,800 genes that include many duplicates.

Wolfe K.H. and Shields D.C. Nature (1997) 387
708-713
43
K. Waltii illuminates the way
S. cerevisiae and K. waltii diverged roughly 150
million years ago, before the genome duplication
event.
Kellis et al. Nature (2004) 428 617-624
44
Gene and region correspondence with K. waltii
reveals genome duplication

• Identified a total of 253 duplicate blocks,
  containing 75 of K. waltii genes and 81 of S.
  cerevisiae genes.
• Duplicate blocks tile 85 of each K. waltii
  chromosome in the pattern expected for WGD.

Kellis et al. Nature (2004) 428 617-624
45
The Map-based approach also suggests a genome
duplication in the Arabidopsis genome

• Segmentally duplicated regions in the Arabidopsis
  genome.
• Much of the genome is in pairs (not in
  triplicates, etc.).
• There is evidence that most (6070) flowering
  plants have a polyploid ancestry

Arabidopsis Genome Initiative. Nature 408,
796815 (2000). Masterston, Science 264, 421423
(1994).
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Temporal Tree-based approach
Genes duplicated simultaneously should show the
same history
Duplication 1
Duplication 2
Wolfe, K.H. Nature Reviews Genetics (2001) 2
333-341
47
The one-to-four rule does not hold up
When the human genome was estimated at 80,000
genes the one-to-four hypothesis was reasonable
but now that the estimate is at 35,000.
...and in 2009, only 25,000.
Makalowski W. Genome Research (2001) 667-670
48
Arguments against 2R

• The one-to-four rule has not been upheld by
  genome sequence data
• Phylogenetic trees for four-membered human gene
  families do not show the excess of ((AB),(CD))
  topologies expected under a 2R model.

A
B
C
D
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GATCTACCATGAAAGACTTGTGAATCCAGGAAGAGAGACTGACTGGGCAA
CATGTTATTCAGGTACAAAAAGATTTGGACTGTAACTTAAAAATGATCAA
ATTATGTTTCCCATGCATCAGGTGCAATGGGAAGCTCTTCTGGAGAGTGA
GAGAAGCTTCCAGTTAAGGTGACATTGAAGCCAAGTCCTGAAAGATGAGG
AAGAGTTGTATGAGAGTGGGGAGGGAAGGGGGAGGTGGAGGGATGGGGAA
TGGGCCGGGATGGGATAGCGCAAACTGCCCGGGAAGGGAAACCAGCACTG
TACAGACCTGAACAACGAAGATGGCATATTTTGTTCAGGGAATGGTGAAT
TAAGTGTGGCAGGAATGCTTTGTAGACACAGTAATTTGCTTGTATGGAAT
TTTGCCTGAGAGACCTCATTGCAGTTTCTGATTTTTTGATGTCTTCATCC
ATCACTGTCCTTGTCAAATAGTTTGGAACAGGTATAATGATCACAATAAC
CCCAAGCATAATATTTCGTTAATTCTCACAGAATCACATATAGGTGCCAC
AGTTATCCCCATTTTATGAATGGAGT2Rornot2R?GATGAAAACCTTAG
GAATAATGAATGATTTGCGCAGGCTCACCTGGATATTAAGACTGAGTCAA
ATGTTGGGTCTGGTCTGACTTTAATGTTTGCTTTGTTCATGAGCACCACA
TATTGCCTCTCCTATGCAGTTAAGCAGGTAGGTGACAGAAAAGCCCATGT
TTGTCTCTACTCACACACTTCCGACTGAATGTATGTATGGAGTTTCTACA
CCAGATTCTTCAGTGCTCTGGATATTAACTGGGTATCCCATGACTTTATT
CTGACACTACCTGGACCTTGTCAAATAGTTTGGACCTTGTCAAATAGTTT
GGAGTCCTTGTCAAATAGTTTGGGGTTAGCACAGACCCCACAAGTTAGGG
GCTCAGTCCCACGAGGCCATCCTCACTTCAGATGACAATGGCAAGTCCTA
AGTTGTCACCATACTTTTGACCAACCTGTTACCAATCGGGGGTTCCCGTA
ACTGTCTTCTTGGGTTTAATAATTTGCTAGAACAGTTTACGGAACTCAGA
AAAACAGTTTATTTTCTTTTTTTCTGAGAGAGAGGGTCTTATTTTGTTGC
CCAGGCTGGTGTGCAATGGTGCAGTCATAGCTCATTGCAGCCTTGATTGT
CTGGGTTCCAGTGGTTCTCCCACCTCAGCCTCCCTAGTAGCTGAGACTAC
ATGCCTGCACCACCACATCTGGCTAGTTTCTTTTATTTTTTGTATAGATG
GGGTCTTGTTGTGTTGGCCAGGCTGGCCACAAATTCCTGGTCTCAAGTGA
TCCTCCCACCTCAGCCTCTGAAAGTGCTGGGATTACAGATGTGAGCCACC
ACATCTGGCCAGTTCATTTCCTATTACTGGTTCATTGTGAAGGATACATC
TCAGAAACAGTCAATGAAAGAGACGTGCATGCTGGATGCAGTGGCTCATG
CCTGTAATCTCAGCACTTTGGGAGGCCAAGGTGGGAGGATCGCTTAAACT
CAGGAGTTTGAGACCAGCCTGGGCAACATGGTGAAAACCTGTCTCTATAA
AAAATTAAAAAATAATAATAATAACTGGTGTGGTGTTGTGCACCTAGAGT
TCCAACTACTAGGGAAGCTGAGATGAGAGGATACCTTGAGCTGGGGACTG
GGGAGGCTTAGGTTACAGTAAGCTGAGATTGTGCCACTGCACTCCAGCTT
GGACAAAAGAGCCTGATCCTGTCTCAAAAAAAAGAAAGATACCCAGGGTC
CACAGGCACAGCTCCATCGTTACAATGGCCTCTTTAGACCCAGCTCCTGC
CTCCCAGCCTTCT
50
Paralogons are defined as paralog pairs separated
by at most 30 intervening genes
A paralogon of size 2 (sm 2)
4 intervening genes (allow for a maximum of 30)
A paralogon of size 3 (sm 3)
Based upon McLysaght et al. Nature Genetics
(2002) 31 200-204
51
Paralogons on human chromosome 17
Modified from McLysaght et al. Nature Genetics
(2002) 31 200-204
52
Distribution of sizes of paralogons found in the
human genome
McLysaght et al. Nature Genetics (2002) 31 200-204
53
Large-scale duplications must be invoked to
explain paralogons Test with a random shuffling
model
Any paralogon with sm ? 6 was very likely to have
been formed by a single duplication
McLysaght et al. Nature Genetics (2002) 31 200-204
54
Dating the duplications with respect to
divergence from fly
outgroup
McLysaght et al. Nature Genetics (2002) 31 200-204
55
Excess duplications in the 0.4-0.7 D date range
McLysaght et al. Nature Genetics (2002) 31 200-204
56
The majority of genes making up paralogons fall
in the age class 0.40.7 D
McLysaght et al. Nature Genetics (2002) 31 200-204
57
One genome duplication seems to have occurred

• Human genome contains many more paralogons than
  expected by chance
• A burst of gene duplication occurred during early
  chordate evolution
• A widespread deletion of genes must have
  subsequently occurred (as in yeast and
  arabidopsis)

McLysaght et al. Nature Genetics (2002) 31 200-204
58
Another study, based upon 749 gene families,
came to a similar conclusion
The authors emphasized both genome and segmental
duplications
Gu X. et al. Nature Genetics (2002) 31 205-209
59
Evolution of the chordate lineage with fly as an
outgroup
Genome duplication estimates
Durand D. TIGs (2003) 19 2-5
60
In the unicellular eukaryote Paramecium
tetraurelia, a ciliate, most of the nearly 40,000
genes arose through at least three successive
whole-genome duplications
Representation of the successive duplications of
the Paramecium genome. The exterior circle
displays all chromosome-sized scaffolds, and the
three interior circles show the reconstructed
sequences obtained by fusion of the paired
sequences from each previous step. Red lines link
pairs of genes with a BRH match, and blue lines
link pairs of genes with a non-BRH match that
were added on the basis of syntenic position.
Only the BRHs that link two genes in the same
paralogon are represented. The position of an
ancestral block is unrelated to the position of
its constituents in the previous circle.
Aury et al. Nature (2006) 444 171-178
61
A model for gradual gene loss after genome
duplications deduced from differential retention
of genes in Paramecium.
Aury et al. Nature (2006) 444 171-178
62
Genome Duplications and Organismal Complexity

• Paleopolyploidy events therefore seem to be
  exceedingly rare
• However, polyploidy is extremely common, 2-3 of
  speciation events.
• This would suggest that, although descendants of
  WGD events do not survive often, when they do
  survive their evolutionary lineage can be very
  successful.

Van de Peer et al. Nature Reviews Genetics (2009)
63
The End
From the book of Bunny Suicides