16th september 2014
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Convergence for everyone? Detecting disparate signals of genomic adaptive convergence in several different datasets: Initial results, lessons & perspectives. 16th September 2014. Joe Parker, Queen Mary University London. Adaptive molecular convergence. Definition Methods to detect - PowerPoint PPT PresentationTRANSCRIPT
Convergence for everyone?Detecting disparate signals of
genomic adaptive convergence in several different datasets:
Initial results, lessons & perspectives
16th September 2014
Joe Parker, Queen Mary University London
Adaptive molecular convergence
• Definition• Methods to detect• Datasets and results• Sampling issues• Interpretational issues• Future
Defining molecular convergence
• Surprisingly hard• It isn’t:
– Divergence (adaptive or neutral)– Conservation or purifying selection– Retention of ancestral states with secondary
changes in outgroups– ‘Neutral’ homoplasy
• It ought to be:– ‘Adaptive’ homoplasies– ‘Excess’ homoplasies
Observations
• ‘Adaptive convergence’ predicated on assumption adaptive sites ‘count’ more - conditions for detection?
• Can parallel changes with dN/dS ~ 1 be ‘convergent’
• ‘Excess’ - a problematic definition without a good null model– Odds-ratio based?– Empirical CDF?– Eyeball…
Methods
• Species phylogeny and inputs• Selection detection• Site-based methods• Tree-based methods
Site-based methods
• Look at tips– Sample balance?
Site-based methods
• Look at tips
• Reconstruct ancestral changes
Site-based methods
• Look at tips• Reconstruct ancestral changes
• Pairwise P(conv) ~ P(div) changes
Site-based methods
• Look at tips• Reconstruct ancestral changes• Pairwise P(conv) ~ P(div) changes
• BEB posterior probabilities
Tree-based methods
• de novo tree search– Inference error– Signal : noise– Multiple phylogenies
Tree-based methods
• ∆SSLS (likelhood comparison)– Which hypotheses?– Multiple simultaneous comparisons?– Models insensitive– How extreme
Tree-based methods
• Unrestricted / ennumerated phylogeny fitting
Trees and sites methods
• dN/dS and ∆SSLS correlation
Trees and sites methods
• Random control tree correction
Genomic approaches
• Pool information across sites– Are loci comparable– Error rates?
• Orthology, paralogy
Sampling
• Sampling balance– Within locus– Between loci
• Gene selection / ascertainment bias• Networks• Tree selection• a priori phylogenies
Convergence in echolocating mammals
• 22 mammals, 2,326 loci• Convergence signals across
genome
Convergence in echolocating bats
• The• The
Convergence in mole-rats
• The• The
Interpretational issues
• Relative measure• Strength of evidence• Null model? Sampling? Which
phylogenies
Interpretation
• Notional convergence detected genomically, or not at all
• Selection, incongruence• Which trees?
Which Trees?
• Choice of hypothesis, subtly different from usual practice
• If we accept tree space distance important…
• … Hypotheses are parameters• Ennumerate over trees?
Future directions
• Null model• Alternative (convergent) model• Tree space distance
Conclusion
• Strong evidence molecular convergence, or something like our best definition of it, is a pervasive force
• Very early work; contrast with e.g. early dN/dS tests
Acknowlegements
• Colleagues• Institutions• Funding
