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Transcript
Genome Rearrangements
Belle marquise, vos beaux yeux me font mourir d'amour.
Vos yeux beaux d'amour me font, belle marquise, mourir.
Me font vos beaux yeux mourir, belle marquise, d'amour.
Anne Bergeron,
Comparative Genomics Laboratory
Université du Québec à Montréal
1. General introduction to genome rearrangements
Examples of rearranged genomes
2. Measures of distance
Rearrangement operations
The Hannenhalli-Pevzner distance equation
3. A unifying view of genome rearrangements
The Double-Cut-and-Join operation
The adjacency graph and the distance equation
1. General introduction to genome rearrangements
Examples of rearranged genomes
2. Measures of distance
Rearrangement operations
The Hannenhalli-Pevzner distance equation
3. A unifying view of genome rearrangements
The Double-Cut-and-Join operation
The adjacency graph and the distance equation
Example of rearranged genomes : Mitochondrial Genomes
Mitochondria are small, oval
shaped organelles surrounded
by two highly specialized
membranes.
Homo sapiens
Bombyx mori
Animal mitochondrial genomes
are normally circular, ~16 kB
in length, and encode:
13 proteins
22 tRNAs and
2 rRNAs.
Example of rearranged genomes : Mitochondrial Genomes
Here is an alignment of the cytochrome c oxidase I
of, respectively, Homo sapiens and Bombyx mori.
RWLFSTNHKDIGTLYLLFGAWAGVLGTALSLLIRAELGQPGNLLGNDHIYNVIVTAHAFVMIFFMVMPIMIGGFGNWLVPLMIGAPDMAFPRMNNM
KWIYSTNHKDIGTLYFIFGIWSGMIGTSLSLLIRAELGNPGSLIGDDQIYNTIVTAHAFIMIFFMVMPIMIGGFGNWLVPLMLGAPDMAFPRMNNM
:*::***********::** *:*::**:**********:**.*:*:*:***.*******:**********************:*************
:X::XXXXXXXXXXX::XX
X:X::XX:XXXXXXXXXX:XX.X:X:X:XXX.XXXXXXX:XXXXXXXXXXXXXXXXXXXXXX:XXXXXXXXXXXXX
SFWLLPPSLLLLLASAMVEAGAGTGWTVYPPLAGNYSHPGASVDLTIFSLHLAGVSSILGAINFITTIINMKPPAMTQYQTPLFVWSVLITAVLLLLSLP
SFWLLPPSLMLLISSSIVENGAGTGWTVYPPLSSNIAHSGSSVDLAIFSLHLAGISSIMGAINFITTMINMRLNNMSFDQLPLFVWAVGITAFLLLLSLP
*********:**::*::** XXXXXXXXXXXX:.X
XXXXXXXXX:XX::X::XX
************:.* :*.*:****:********:***:********:***:
:X.X:XXXX:XXXXXXXX:XXX:XXXXXXXX:XXX:
*:
X: *
X *****:*
XXXXX:X ***.*******
XXX.XXXXXXX
VLAAGITMLLTDRNLNTTFFDPAGGGDPILYQHLFWFFGHPEVYILILPGFGMISHIVTYYSGKKEPFGYMGMVWAMMSIGFLGFIVWAHHMFTVGMDVD
VLAGAITMLLTDRNLNTSFFDPAGGGDPILYQHLFWFFGHPEVYILILPGFGMISHIISQESGKKETFGCLGMIYAMLAIGLLGFIVWAHHMFTVGMDID
***..************:***************************************:: *****.**
XXX..XXXXXXXXXXXX:XXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXXX::
XXXXX.XX :**::**::**:****************:*
:XX::XX::XX:XXXXXXXXXXXXXXXX:X
TRAYFTSATMIIAIPTGVKVFSWLATLHGSNMKWSAAVLWALGFIFLFTVGGLTGIVLANSSLDIVLHDTYYVVAHFHYVLSMGAVFAIMGGFIHWFPLF
TRAYFTSATMIIAVPTGIKIFSWLATMHGTQINYNPNILWSLGFVFLFTVGGLTGVILANSSIDITLHDTYYVVAHFHYVLSMGAVFAIIGGFINWYPLF
*************:***:*:******:**:::::.. :**:***:**********::*****:**.***********************:****:*:***
XXXXXXXXXXXXX:XXX:X:XXXXXX:XX:::::..
:XX:XXX:XXXXXXXXXX::XXXXX:XX.XXXXXXXXXXXXXXXXXXXXXXX:XXXX:X:XXX
SGYTLDQTYAKIHFTIMFIGVNLTFFPQHFLGLSGMPRRYSDYPDAYTTWNILSSVGSFISLTAVMLMIFMIWEAFASKRKVLMVEEPSMNLE
TGLSLNSYMLKIQFFTMFIGVNMTFFPQHFLGLAGMPRRYSDYPDSYISWNMISSLGSYISLLSVMMMLIIIWESMINQRINLFSLNLPSSIE
:* :X:.
:X
:*:.
XX:X
**:* XXXXXX:XXXXXXXXXX:XXXXXXXXXXX:X
******:**********:***********:* :**::**:**:***
:XX::XX:XX:XXX :**:*:::***::
:XX:X:::XXX:: .:*
.:X *:
X: : . .:*
.:X
73% identity over more than 500 amino acids.
Example of rearranged genomes : Mitochondrial Genomes
The 37 genes of animal
mitochondria are highly
conserved.
Charles Darwin, 1809 - 1882
A lowly worm
But the order of the genes
differs from species to
species.
Example of rearranged genomes : Mitochondrial Genomes
The invariant parts
Homo sapiens mitochondrial genome (proteins and rRNAs)
COX1 COX2 ATP6
ATP8
COX3
ND3
ND4L
ND4
ND5
CYTB
RNS
RNL
ND1
ND2
ND6
COX1 stands for the gene
cytochrome c oxidase I.
Bombyx mori mitochondrial genome (proteins and rRNAs)
COX1 COX2 ATP6
ATP8
COX3
ND3
ND6
ND5
COX1 stands for the gene
cytochrome c oxidase I.
ND4
ND4L
CYTB
ND2
ND1
RNL
RNS
Example of rearranged genomes : Mitochondrial Genomes
The modified parts
Homo sapiens mitochondrial genome (proteins and rRNAs)
COX1 COX2 ATP6
ATP8
COX3
ND3
ND4L
ND4
ND5
CYTB
RNS
RNL
ND1
ND2
ND6
Bombyx mori mitochondrial genome (proteins and rRNAs)
COX1 COX2 ATP6
ATP8
COX3
ND3
ND6
ND5
ND4
ND4L
CYTB
ND2
ND1
RNL
RNS
Example of rearranged genomes : Mitochondrial Genomes of 6
Arthropoda
Fruit Fly
Mosquito
Silkworm
Locust
Tick
Centipede
Identical ‘runs’ of genes have been grouped.
Example of rearranged genomes : mammal X chromosomes
Sixteen large synteny
blocks are ordered
differently in the X
chromosomes of the
human, mouse and rat.
Blocks have similar gene
content and order.
Note that the estimated
number of genes in the X
chromosome is 2000.
(Art work by Guillaume Bourque,
scientific work by Guillaume Bourque,
Pavel Pevzner and Glenn Tesler, 2004)
Example of rearranged genomes : mammal X chromosomes
QuickTime™ and a
decompressor
are needed to see this picture.
(Art work by Guillaume Bourque,
scientific work by Guillaume Bourque,
Pavel Pevzner and Glenn Tesler, 2004)
Problem: Given two or more genomes,
How do we measure their similarity and/or
distance with respect to gene order and
gene content?
Sub-problem: How do we know
that two genes or blocks are the
"same" in two different species?
1. General introduction to genome rearrangements
Examples of rearranged genomes
2. Measures of distance
Rearrangement operations
The Hannenhalli-Pevzner distance equation
3. A unifying view of genome rearrangements
The Double-Cut-and-Join operation
The adjacency graph and the distance equation
Rearrangement operations
Rearrangement operations affect gene order
and gene content. There are various types:
• Inversions
• Transpositions
• Reverse transpositions
• Translocations, fusions and fissions
• Duplications and losses
• Others...
Any set of operations yields a distance between
genomes, by counting the minimum number of
operations needed to transform one genome into
the other.
Rearrangement operations
• Inversions
Rearrangement operations
• Inversions
Rearrangement operations
• Inversions
Example: Mitochondrial Genomes of 6 Arthropoda
An inversion.
Fruit Fly
Mosquito
Silkworm
Locust
Tick
Centipede
Rearrangement operations
• Transpositions
Rearrangement operations
• Transpositions
Rearrangement operations
• Transpositions
Example: Mitochondrial Genomes of 6 Arthropoda
Fruit Fly
Mosquito
Silkworm
Locust
Tick
A transposition
Centipede
Rearrangement operations
• Reverse transpositions
Rearrangement operations
• Reverse transpositions
Rearrangement operations
• Reverse transpositions
Example: Mitochondrial Genomes of 6 Arthropoda
Fruit Fly
Mosquito
Silkworm
Locust
A reverse transposition
Tick
Centipede
Rearrangement operations
• Translocations, fusions and fissions
Rearrangement operations
• Translocations, fusions and fissions
Rearrangement operations
• Translocations, fusions and fissions
Rearrangement operations
• Translocations, fusions and fissions
Rearrangement operations
• Translocations, fusions and fissions
Rearrangement operations
• Translocations, fusions and fissions
From 24
chromosomes
To 21
chromosomes
[Source: Linda Ashworth, LLNL]
DOE Human Genome Program Report
1. General introduction to genome rearrangements
Examples of rearranged genomes
2. Measures of distance
Rearrangement operations
The Hannenhalli-Pevzner distance equation
3. A unifying view of genome rearrangements
The Double-Cut-and-Join operation
The adjacency graph and the distance equation
The Hannenhalli-Pevzner distance equation
In 1995, Hannenhalli and Pevzner found a formula to
compute the minimum number of inversions,
translocations, fusions or fissions necessary to
transform a multichromosomal genome into another.
Sketch of the approach:
• Cap the chromosomes
• Concatenate all the chromosomes
• Sort the resulting genome by inversions
QuickTime™ and a
decompressor
are needed to see this picture.
1. General introduction to genome rearrangements
Examples of rearranged genomes
2. Measures of distance
Rearrangement operations
The Hannenhalli-Pevzner distance equation
3. A unifying view of genome rearrangements
The Double-Cut-and-Join operation
The adjacency graph and the distance equation
The Double-Cut-and-Join operation
Acts on up to 4 gene extremities:
,
,
,
Reminder
Yancopoulos et al. 2005
The Double-Cut-and-Join operation
Linear chromosomes
Translocation
Translocation
Translocation
Translocation
Reminder
Translocation
Translocation
The Double-Cut-and-Join operation
Linear and circular chromosomes
Inversion
Inversion
Fusion
Fusion
Fission
Reminder
Fission
The Double-Cut-and-Join operation
Circular chromosomes
Inversion
Inversion
Fusion
Fusion
Fission
Reminder
Fission
1. General introduction to genome rearrangements
Examples of rearranged genomes
2. Measures of distance
Rearrangement operations
The Hannenhalli-Pevzner distance equation
3. A unifying view of genome rearrangements
The Double-Cut-and-Join operation
The adjacency graph and the distance equation
4. Breakpoint reuse
Breakpoint reuse estimates
Minimizing breakpoint reuse
The adjacency graph and the distance equation
Genome A
3
5
2
4
1
6
Genome B
1
2
5
Joint work with Julia Mixtacki and Jens Stoye
3
6
4
The adjacency graph and the distance equation
Genome A
Genome B
3
1
5
2
2
3
Joint work with Julia Mixtacki and Jens Stoye
4
4
1
5
6
6
The adjacency graph and the distance equation
Genome A
Genome B
3
1
5
2
2
3
Joint work with Julia Mixtacki and Jens Stoye
4
4
1
5
6
6
The adjacency graph and the distance equation
Genome A
Genome B
3
1
5
2
2
3
Joint work with Julia Mixtacki and Jens Stoye
4
4
1
5
6
6
The adjacency graph and the distance equation
Genome A
Genome B
3
1
5
2
2
3
Joint work with Julia Mixtacki and Jens Stoye
4
4
1
5
6
6
The adjacency graph and the distance equation
Genome A
Genome B
3
1
5
2
2
3
Joint work with Julia Mixtacki and Jens Stoye
4
4
1
5
6
6
The adjacency graph and the distance equation
Genome A
Genome B
3
1
5
2
2
3
C = number of cycles
I = number of odd paths
G = number of “genes”
Joint work with Julia Mixtacki and Jens Stoye
4
4
1
5
D = G - (C + I/2)
D = 6 - (1 + 2/2) = 4
6
6