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A presentation about evolutionary genomics, showing a selection of examples of what information can be extracted from genomes.
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LBBE, CNRS, Université de Lyon
Evolutionary genomics
Bastien Boussau
@bastounette
Chance and necessity
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Chance and necessity
… …Evolution
…ATCGACATCAGCATCAGCACTAC…
Chance and necessity
… …Evolution
Function
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Evolution in our genomes
3
Brown, Sanger, Kitai. Biochem. J. 1955.
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Evolution in our genomes
3
Brown, Sanger, Kitai. Biochem. J. 1955.
3
Evolution in our genomes
3
Brown, Sanger, Kitai. Biochem. J. 1955.
Genomes as Documents of Evolutionary History
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What information can we extract from genome sequences?
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1. Species phylogeny!
2. Phylogeography!
3. Diversification history!
4. Ancestral lifestyles!
5. Selective pressures in extant species!
6. Application to cell lineages
Genome evolution
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Genome sequence
Processes
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Genome evolution
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Genome sequence
point mutations
Processes
…ACTCGTTCGCATCGACTCCTCCAGC…
Genome evolution
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Genome sequence
point mutations
Processes
…ACTCGATCGCATCGACTCCTCCAGC…
Genome evolution
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Genome sequence
point mutations insertions/deletions
Processes
…ACTCGATCGCATCGAAAACTCCTCCAGC…
Genome evolution
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Genome sequence
point mutations insertions/deletions
Processes
…ACTCGATCGCATCGACTCCTCCAGC…
Genome evolution
8
Genome sequence
point mutations insertions/deletions duplications/losses
Processes
…ACTCGATCGCATCGACTCCTTCCTCCAGC…
Genome evolution
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Genome sequence
point mutations insertions/deletions duplications/losses
Processes
…ACTCGATCGCATCGACTCCTCCAGC…
Genome evolution
9
Genome sequence
point mutations insertions/deletions duplications/losses rearrangements
Processes
…ACTCGATCGCAAGCTCTCCTCCAGC…
Genome evolution
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Genome sequence
point mutations insertions/deletions duplications/losses rearrangements
Processes
population genetics molecular machinery species phylogeny environment
…ACTCGATCGCATCGACTCCTCCAGC…
Using genomes for statistical inference
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Genome sequence
point mutations insertions/deletions duplications/losses rearrangements
Processes
population genetics molecular machinery species phylogeny environment
…ACTCGATCGCATCGACTCCTCCAGC…
Inferential statistics
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Boussau and Daubin, Tree 2010
Inferential statistics
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Boussau and Daubin, Tree 2010
• Using computers!• Probabilistic models (e.g. models of sequence evolution)!• “What I cannot create, I do not understand.” (Feynman, 1988)!• What I cannot simulate, I do not understand.”
What information can we extract from genome sequences?
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1. Species phylogeny!
2. Phylogeography!
3. Diversification history!
4. Ancestral lifestyles!
5. Selective pressures in extant species!
6. Application to cell lineages
1 Inferring the phylogeny
Models:!
• Modelling events of substitution!
• In some cases, modelling insertions and deletions!
• In some cases, modelling allele sorting!
• In some cases, modelling gene duplications, losses and transfers!
• In some cases, modelling hybridization!
• Dates of speciation can also be inferred with a model of rate evolution
1 The phylogeny of life
Williams et al., Nature 2013
1 The phylogeny of life
Williams et al., Nature 2013
Improvements in:!• probabilistic models!• data available
1 The origin of viral strains
Boussau, Guéguen, Gouy, Evolutionary Bioinformatics 2009.
1353 first sites ~1200 remaining sites
1 The origin of viral strains
Boussau, Guéguen, Gouy, Evolutionary Bioinformatics 2009.
The N HIV strain originated through a recombination between a Human and a Chimp virus
1353 first sites ~1200 remaining sites
Contagion, Steven Soderbergh, 2011
Contagion, Steven Soderbergh, 2011
1 Forensic analyses
Scaduto et al., PNAS 2010
The problem:!
• CC01 is a HIV-positive male, accused by several partners of hiding
his seropositivity and infecting them in the process ==> trial!
• 1 accused male, 6 partners, all seropositive!
• HIV sequences available from each of them!
• How can we tell whether CC01 likely contaminated his partners?
1 Forensic analyses
Scaduto et al., PNAS 2010
The problem:!
• CC01 is a HIV-positive male, accused by several partners of hiding
his seropositivity and infecting them in the process ==> trial!
• 1 accused male, 6 partners, all seropositive!
• HIV sequences available from each of them!
• How can we tell whether CC01 likely contaminated his partners?
Use the HIV sequences to build a phylogenetic tree!
1 Forensic analyses
Scaduto et al., PNAS 2010
1 Forensic analyses
Scaduto et al., PNAS 2010
Evidence used to establish that CC01 had infected his partners
1 Inferring the phylogeny
Purposes:!
• Inferring the species phylogeny!
• Reconstructing the evolutionary history of infectious agents!
• Reconstructing transmission histories (e.g. forensic analyses)!
2 Phylogeography
Question:!• How did these organisms get to be where they are?!
2 Phylogeography
Question:!• How did these organisms get to be where they are?!
Mus musculus, GBIF database
2 Phylogeography
Faria et al., Science 2014
Models:!• Add spatial information at the leaves!• Use Discrete models or continuous models to reconstruct
ancestral ranges!
2 Phylogeography
Landis et al., Syst. Biol. 2014
Landis et al., Syst. Biol. 2014
2 Phylogeography
2 HIV phylogeography
Faria et al., Science 2014
2 Phylogeography
Purposes:!
• Inferring the species geographical range through time!
• Reconstructing the evolutionary spread of infectious agents!
• Investigating plate tectonics!
3 Diversification history
How did species diversify? Were there bursts of speciation, or
mass extinctions? !
How many species/individuals through time?!
Models:!
• Modelling events of speciation, and events of extinction!
• In some cases, can be dependent on other parameters
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3 Species of birds through time
Jetz et al., Nature 2012
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3 Speciations of birds across the globe
Jetz et al., Nature 2012
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3 Phylodynamics of HCV in Egypt
Drummond et al., MBE 2005
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3 Phylodynamics of HCV in Egypt
Drummond et al., MBE 2005
Huge increase in number of viruses coincides with the extensive use of an antischistosomiasis treatment from 1920 to 1980
3 Diversification history
Purposes:!
• Inferring the number of species/individuals through time!
• Finding major radiation/extinction events!
• Reconstructing past epidemics!
4 Ancestral lifestyles
How did ancestral species live? What temperature did they
like most? How long did they live?!
Models:!
• Correlating molecular evolution with phenotypic traits!
4 Inferring growth temperature across the tree of life
4 Inferring growth temperature across the tree of life
Idea: reconstruct ancestral sequences in silico, and predict ancestral growth temperatures
4 Inferring growth temperature across the tree of life
Usual model: !all branches evolve according to the same model
Better model: !different models for different branches
Boussau et al., Nature 2008
4 Inferring growth temperature across the
tree of life
Boussau et al., Nature 2008
4 Inferring growth temperature across the tree of life
Boussau et al., Nature 2008
4 Inferring growth temperature across the tree of life
Late Heavy Bombardment 3.8 Bya?
Lartillot and Delsuc, Evolution 2012
4 Joint inference of rates, dates, and traits
4 Ancestral lifestyles
Purposes:!
• Inferring characteristics of ancient organisms!
• Inferring characteristics of ancient environments!
• Finding/using correlations between phenotype evolution and
genotype evolution
5 Selective pressures in extant species
What sites in the genome of species X are important?!
Models:!
• Usual models of sequence evolution!
• Models of insertion-deletion!
• Hidden Markov Models that run along the genome!
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5 Conservation across species indicates function
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Brown, Sanger, Kitai. Biochem. J. 1955.
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5 Conservation across species indicates function
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The UCSC genome browser uses conservation across 100 vertebrates to detect functional regions
Gnad et al., BMC Genomics 2013
5 How to best predict cancer-
causing mutations?
Comparison across 12 methods:
5 How to best predict cancer-causing mutations?
Gnad et al., BMC Genomics 2013
5 Selective pressures in extant species
Purposes:!
• Screening a genome for new functional elements!
• Evaluating the severity of candidate mutations (e.g. genetic
disease, cancer)!
• Finding sites to target in a pest that needs controlling
6 Application to cell lineages
As cells divide by mitosis, mutations accumulate. !—> phylogenetic approaches can be used to address developmental questions:!• How similar is development across individuals?!• Do the first cells produced during development contribute equally to
the adult organism?!• …!Models:!• Usual models of sequence evolution!• Models of microsatellite evolution
6 Application to cell lineages
Behjati et al., Nature 2014
6 Application to cell lineages
Behjati et al., Nature 2014
Contributions of early embryonic cells to adult tail cell populations
6 Application to cell lineages
6 Application to cell lineages
Purposes:!
• Learning about development!
• Learning about cancer evolution (e.g. using phylogeography to
understand cancer spread)
Conclusions
• Genomes contain a lot of information about their history and about how they work!
• The comparative approach is a powerful way to learn about the function of a stretch of sequence!
• Thanks to probabilistic models, one can exploit the huge amount of information in genomes to ask a large number of interesting questions
Slides available on SlideShare: http://www.slideshare.net/boussau
