29 mammalian genomes
TRANSCRIPT
A
High-Resolution Map of
Evolutionary Constraint
In the human genome
by Lindblad-Toh & colleagues, Nature 2011
Presented by Nacho Caballero
Constrained Diversity
Is the Key to Comparative Genomics
Average # of Subs. per Site (Branch Length) 0.8 1.25 1.5 3 5
1+ subs 2+ subs 3+ subs 4+ subs
1 -
0.5 -
0 -
Percentage of Sites that Have Undergone Substitutions
0 1 2 3 4 6 5 Number of Neutral Substitutions per Site
0.5 -
0.3 -
0.1 -
0.8 subs/site 1.25 subs/site
3 subs/site 5 subs/site
1.5 subs/site
Percentage of Sites that Have Undergone Substitutions
4 Genomes - 50 bp
29 Genomes – 12 bp
4 genomes 29 genomes
NPAS4
Individual Binding Sites Higher Resolution Uncovers
bias
start stop
Evolutionary Signatures Help Discover Novel Genes
Synonymous Substitution Non-Synonymous Substitution
Frame-Preserving Indel Frame-shifting Indel
Stop Codons
Annotated as an Intron
Identify Stop-Codon Readthrough
1st stop codon 2nd stop codon
SACM1L
Synonymous Substitution Non-Synonymous Substitution
Frame-Preserving Indel Frame-shifting Indel
Stop Codons
Evolutionary Signatures Help
Identify Stop-Codon Readthrough
1st stop codon
2nd stop codon
Evolutionary Signatures Help
A Richer Picture of Conservation: Synonymous Constrained Elements
HOXA2
Basewise Conservation
Synonymous Constrained Rate
Enhancer Enhancer
A Richer Picture of Conservation: Codon-Specific Selection
dN/dS = 1 Neutral Selection dN/dS < 0.5 Purifying Selection
dN/dS > 1.5 Positive Selection
dN/dS = 1 Neutral Selection dN/dS < 0.5 Purifying Selection
dN/dS > 1.5 Positive Selection
A Richer Picture of Conservation: Codon-Specific Selection
dN/dS = 1 Neutral Selection dN/dS < 0.5 Purifying Selection
dN/dS > 1.5 Positive Selection
A Richer Picture of Conservation: Codon-Specific Selection
40% of the Constrained Genome
Is Uncharted territory
Constrained Diversity Is the Key to
Comparative Genomics
100-200 Mammalian Genomes
Will Allow Single-Nt Resolution