Download Gene duplication and rearrangement

Genome evolution
• There are both proximate and ultimate
explanations in molecular biology
• Mutation continually generates variation
in genome content and structure
– Raw material for natural selection
– Potential for non-adaptive evolution
• Function is too blunt a concept for
genome evolution
The genome as phenotype
• Evolutionary biologists study both pattern
and process, or mechanism
• What unexpected patterns do we see
– Within genomes?
– By comparisons among them?
• What can we infer about proximal and
ultimate mechanisms by
– Catching evolution red-handed?
– Testing genome evolutionary models?
Three open questions
1. How rapidly do the expression profiles
of duplicated genes diverge?
2. What is the extent of polymorphism in
gene order within species?
3. What is responsible for physical
clusters of co-expressed genes?
Three open questions
1. How rapidly do the expression profiles
of duplicated genes diverge?
2. What is the extent of polymorphism in
gene order within species?
3. What is responsible for physical
clusters of co-expressed genes?
Arabidopsis MPSS
• With Blake Meyers and Barry Kesner
• Massively parallel signature sequencing
– Bead based expression monitoring
– Estimates for nearly all genes
– Estimates are good even at low expression
• Sample eight tissues from Arabidopsis
thaliana
• Couple with genome-wide phylogenetic
analysis of duplicated genes
Measuring expression distance
Tissue 2
Tissue 1
Tissue 3
Measuring duplication age
Athal1
Athal2
T1
T2
Rice
Divergence between duplicates
Age of duplication
Does the pattern differ for
• Tandem duplicates?
• Transposed duplicates?
• Polyploidy remnants?
Three open questions
1. How rapidly do the expression profiles
of duplicated genes diverge?
2. What is the extent of polymorphism in
gene order within species?
3. What is responsible for physical
clusters of co-expressed genes?
Gene order polymorphism
• With Jason Lieb and Jennifer Kriss
• Using high-throughput methods to compare
gene order in two yeast strains
• One strain known to lack 7 ORFs present in
the reference genome
• The key ingredients
– Comparative genomic hybridization to a wholegenome chip
– Whole-genome genotyping in multiple haploid
recombinants from a cross between the two
strains
Comparative genomic
hybridization on a chip
Detecting gene transposition
• Genes that are in different chromosomal
positions in the two strains will appear
as deletions and amplifications in the
recombinant progeny
Stay tuned!
Three open questions
1. How rapidly do the expression profiles
of duplicated genes diverge?
2. What is the extent of polymorphism in
gene order within species?
3. What is responsible for physical
clusters of co-expressed genes?
Natural selection and clusters
of co-expressed genes
• With Jianhua Hu
• Neighboring genes with similar
expression profiles are more common
than expected in C. elegans
• Two classes of explanation
– Adaptive: more efficient, less error-prone
– Maladaptive: due to recent transpositions
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
• The effectiveness of natural selection is
directly related to recombination rate
• Are clusters found in regions of high
recombination (adaptive) or low
(maladaptive)?
Measuring the co-expression
of neighboring genes
• Measure the distance in expression space
from central gene to each neighbor
• If neighboring genes are co-expressed, the
average of these distances will be smaller
than for non-neighboring genes
d1
d2
d3
X
d4
Sizes of co-expressed clusters
Measuring recombination rate
Expression distance and
recombination rate
Spearman = -0.07
p = 0.0005
Opportunities abound!
• The field of genome evolution is a vast
and open playing field
– Gads of genome data
– Some seriously cool experimental
techniques
– A golden age in bioinformatics and
molecular evolution