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Outline
• Arabidopsis gene expression (MPSS)
• Two evolutionary issues in the evolution of
expression profiles:
– Physical clustering of co-expressed genes
– Divergence of duplicated genes
Physical clustering of co-expression
Caenorhabditis elegans
Drosophila melanogaster
Homo sapiens
Saccharomyces cerevisiae
Roy et al., (2002) Nature 418, 975
Lercher et al (2003) Genome Research 13, 238
Boutanaev et al (2002) Nature 420, 666
Spellman and Rubin (2002) J Biology 1, 5
Caron et al (2001) Science 291, 1289
Lercher et al (2002) Nature Genetics 31, 180
Cohen et al (2000) Nature Genetics 26, 183
Hurst et al (2002) Trends in Genetics 18, 604
Mannila et al (2002) Bioinformatics 18, 482
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• What are the proximate explanations?
– shared cis-regulatory elements
– chromatin packaging, etc.
• What are the ultimate explanations?
– Adaptive: greater transcriptional efficiency/accuracy?
– Maladaptive: mutational rain chipping away at insulators and other
mechanisms that over-ride regional controllers of gene expression?
Measuring expression distance
library 2
library 1
library 3
Clustering of tissue-specific expression
Chromosome 1
Flower (red)
Silique (violet)
Leaf (green)
Root (blue)
Callus (white)
Statistical tests of coexpression clustering
• Measured median pairwise expression distance
(MPED) in non-overlapping windows of 20 genes
– Summed unique class 1 and 2 signatures for each gene
– Only one gene within each tandemly arrayed family
was counted
• Out of 100 shuffles of gene order
– Zero shuffles had as many windows with small MPED
(less than 1.5) as the unshuffled data
– Zero shuffles had as large a variance in MPED among
windows as the unshuffled data
Coexpression in Arabidopsis
Coexpression in Arabidopsis
Coexpression in Arabidopsis
Selection and recombination
• In regions of low recombination
– deleterious mutations can hitch-hike to high frequency
along with favorable ones
– favorable mutations are kept at low frequency by
linkage to deleterious ones
• Therefore, the effectiveness of natural selection is
causally related to recombination rate
• Are clusters more concentrated in regions of
– high recombination (i.e. are they adaptive)
– low (i.e. are they maladaptive)?
Measuring recombination rate
Chromosome 1
9
genetic distance (cm)
8
100
7
80
6
5
60
4
40
3
2
20
1
0
0
0
5
10
15
20
physical distance (Mb)
25
30
35
recombination rate (cm/Mb)
120
3.5
3
recombination rate (cm/Mb)
>10
10
9
8
7
6
5
4
3
2.5
2
expression distance
Co-expression is greater in low
recombination regions
Co-expression clusters
• MPSS data provides evidence for clusters of
co-expression among non-related genes in
Arabidopsis
• Co-expression is greater in regions of low
recombination
• Thus, co-expression clusters may be
maladapative, at least on average
Outline
• Arabidopsis gene expression (MPSS)
• Two evolutionary issues in the evolution of
expression profiles:
– Physical clustering of co-expressed genes
– Divergence of duplicated genes
Divergence of duplicated genes
Age of duplication
Duplicated genes in Arabidopsis
Modes of gene duplication
• Tandem (unequal crossing-over)
• Dispersed (transposition)
• Segmental (polyploidy)
Divergence of duplicated genes
• All gene families of size 2 in Arabidopsis
were classified as ‘dispersed’, ‘segmental’
or ‘tandem’
• Expression distance was calculated for each
• The number of silent (i.e. synonymous)
substitutions per site was calculated for
each (as a proxy for age since duplication)
expression distance
Divergence and mode of duplication
4
3
2
dispersed
segmental
tandem
1
0
0
2
4
6
silent substitutions (per site) x 10
8
Divergence of duplicated genes
• Almost all expression divergence occurs during
(or immediately following) duplication
• Initial expression divergence is more extreme for
tandem than dispersed duplicates
• Tandem and dispersed duplicates with the most
divergent expression profiles are quickly lost
• Segmental duplicates plateau at a lower level of
expression divergence than dispersed duplicates
• The average divergence in relative expression
level in each tissue is about 8-fold.
Lessons learned
• Clusters of co-expression in Arabidopsis
may be largely the result of a rain of weakly
deleterious mutations that homogenize the
expression profiles of neighboring genes
• Divergence in expression profile between
duplicated genes is dependent on the nature
of the mutation that gave rise to the
duplication