1、Adaptationism and the Adaptive Landscape,Genomic imprinting, mathematical models, and notions of optimality in evolution,Overview,Adaptationism Zoom and Grain in the adaptive landscape Mathematical models of genomic imprinting,Adaptationism,Primary role for natural selection in evolution versus drif
2、t, historical and developmental constraints, etc.Modern debate framed by the Sociobiology wars (Wilson, Dawkins, Lewontin, Gould, etc.)Continuation with Evolutionary Psychology, but Partial reconciliation in most fields Tests of selection, contemporary systematics,Types of adaptationism,Empirical Ce
3、ntral causal role for selection Explanatory Selection answers the big questions Methodological Selection is a good organizing conceptGodfrey-Smith (2001),The Adaptive Landscape,Natural selection is conceived of as a hill-climbing algorithm,Caveats,Units (genotype vs. phenotype, population vs. indivi
4、dual fitness) High dimensionality Topology of the landscape Dependence on other organisms Hill-climbing metaphor implies a deterministic process,Zoom level 1,High level analyses invoke rugged landscapes, which emphasize the role of historical contingency,Zoom level 2,Intermediate levels of analysis
5、focus on local regions with a small number of peaks, emphasizing optimization,Zoom level 3,Low-level analyses reveal the discontinuities in the fitness landscape, emphasizing drift, recombination, etc.,Zoom level 3,Low-level analyses reveal the discontinuities in the fitness landscape, emphasizing d
6、rift, recombination, etc.,Sickle-cell anemia,HbA / HbA Susceptible HbA / HbS Resistant HbS / HbS Sickle-cell,Resistant parents,Susceptible,Resistant,Sickle-cell,Population-genetic timescale,Mendelian segregation recreates sub-optimal phenotypes every generation,HbA / HbS,HbA / HbA,HbS / HbS,100 gene
7、rations,Mutation timescale,The mutation giving rise to the HbS allele represents a partial adaptation to malaria,HbA + HbS,HbA,104 generations,Chromosomal rearrangement timescale,A (hypothetical) rearrangement could give rise to a single chromosome containing both the HbA and HbS alleles. This new a
8、llele should sweep to fixation.,108 generations,Immune-system evolution timescale,In principle, we could ask why our immune system is susceptible to malaria at all.,HbA + HbS,HbA,Ig-,HbAS,IgM IgA IgG IgE,1010+ generations,Genomic Imprinting,Non-equivalence of maternal and paternal genomesNormal deve
9、lopment in mammals requires both,Genomic Imprinting,Epigenetic differences result in differences in expressionDNA methylation reversible chemical modification of the DNA,Oogenesis,Spermatogenesis,Reciprocal heterozygotes are non-equivalent,Conflict over resources,Asymmetries in relatedness,Paternal
10、expression,Maternal expression,Maternal optimum,Paternal optimum,Growth-enhancing locus,Unimprinted gene,Cis-acting maternal modifiers,Cis-acting paternal modifiers,Conflict over resources,Paternal expression,Maternal expression,Paternal optimum,Maternal optimum,Growth-suppressing locus,Unimprinted
11、gene,Cis-acting maternal modifiers,Cis-acting paternal modifiers,Conflict over resources,Game-theoretic / stability analysis models of imprinting,X - expression level Wm - matrilineal fitness Wp - patrilineal fitness U - individual fitness V - fitness of other offspring G - resource demand C - cost
12、of gene expression 2p - fraction of mothers offspring with the same father,Growth enhancer:,Population-genetic models,Two sibs, paternal imprintingA - unimprinted allele a - imprintable allelea = A when maternally inherited a - (a) when paternally inheritedAA = aA a(a) = A(a),Fitness of unimprinted
13、sibs: 1 e.g., AA, AA Fitness if both imprinted: 1+u e.g., a(a), A(a) If only one is imprinted: e.g., AA & A(a) Imprinted fitness: 1-s for A(a) Unimprinted fitness: 1+t for AA,Population-genetic models,Parameters: allele frequencies, fitnesses, frequency of multiple paternity Spencer, Feldman, and Cl
14、ark 1998 Genetics,Population-genetic models,Two sibs, paternal imprintingA - unimprinted allele a - imprintable allelea = A when maternally inherited a - (a) when paternally inheritedAA = aA a(a) = A(a),Fitness of unimprinted sibs: 1 e.g., AA, AA Fitness if both imprinted: 1+u e.g., a(a), A(a) If on
15、ly one is imprinted: e.g., AA & A(a) Imprinted fitness: 1-s for A(a) Unimprinted fitness: 1+t for AAMonandrous females: a invades A if u s a stable if u t/2 Polyandrous females: a invades A if s t/2,Predictions and contradictions,Game-theoreticImprinting requires multiple paternity (p 1/2) Allele fa
16、voring lower expression will be completely silenced maternal silencing of growth enhancers paternal silencing of growth suppressors,Population-geneticParticular combinations of s, t, and u can produce stable polymorphisms Multiple paternity is not required Maternal silencing for growth enhancers is
17、more likely, but paternal silencing can occur,Paternal expression,Maternal expression,Maternal optimum,Paternal optimum,Growth-enhancing locus,Unimprinted gene,Cis-acting maternal modifiers,Cis-acting paternal modifiers,Paternally silenced growth enhancer,Reduced paternal expression would be favored
18、 from these points,Key assumption,Game-theoretic models assume that the unimprinted expression level is at its optimum before the introduction of an imprinted alleleIs this assumption a good one?Gene expression array analyses of population-level variation reveal a high level of variationThis implies
19、 a good opportunity for selection to find the optimum,Separation of timescales in the evolution of imprinting,Unimprinted alleles are restricted to a subspace in the fitness landscape,Imprinting opens up a new dimension in strategy space,If mutations that quantitatively change gene expression are mu
20、ch more common than those that give rise to imprinting, imprinting will always arise in the context of an optimized expression level,Take-home message,Choice of a particular modeling framework implies certain assumptions that can affect your interpretation of your resultsWhen smart people doing reasonable things disagree, there is probably something interesting going on,
