1. Adaptationism and the Adaptive Landscape
Genomic imprinting, mathematical models, and notions of optimality in evolution

2. Overview Adaptationism Zoom and Grain in the adaptive landscape
Mathematical models of genomic imprinting

3. Adaptationism Primary role for natural selection in evolution
versus drift, 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

4. Types of adaptationism
Empirical
Central causal role for selection
Explanatory
Selection answers the big questions
Methodological
Selection is a good organizing concept
Godfrey-Smith (2001)

5. The Adaptive Landscape
Natural selection is conceived of as a hill-climbing algorithm

6. Caveats
Units (genotype vs. phenotype, population vs. individual fitness)
High dimensionality
Topology of the landscape
Dependence on other organisms
Hill-climbing metaphor implies a deterministic process

7. Zoom level 1
High level analyses invoke rugged landscapes, which emphasize the role of historical contingency

8. Zoom level 2
Intermediate levels of analysis focus on local regions with a small number of peaks, emphasizing optimization

9. Zoom level 3
Low-level analyses reveal the discontinuities in the fitness landscape, emphasizing drift, recombination, etc.

10. Zoom level 3
Low-level analyses reveal the discontinuities in the fitness landscape, emphasizing drift, recombination, etc.

11. Sickle-cell anemia HbA / HbA HbA / HbS HbS / HbS Susceptible Resistant
parents
Susceptible
Resistant
Sickle-cell

12. Population-genetic timescale
HbA / HbS
HbA / HbA
HbS / HbS
~100 generations
Mendelian segregation recreates sub-optimal phenotypes every generation

13. Mutation timescale ~104 generations HbA + HbS HbA
The mutation giving rise to the HbS allele represents a partial adaptation to malaria

14. Chromosomal rearrangement timescale
HbA + HbS
HbA
HbAS
~108 generations
A (hypothetical) rearrangement could give rise to a single chromosome containing both the HbA and HbS alleles. This new allele should sweep to fixation.

15. Immune-system evolution timescale
IgM
IgA
IgG
IgE
HbAS
Ig-
HbA + HbS
HbA
~1010+ generations
In principle, we could ask why our immune system is susceptible to malaria at all.

16. Genomic Imprinting Non-equivalence of maternal and paternal genomes
Normal development in mammals requires both
a1 a2 ≠ a2 a1
additional information besides DNA
cloning

17. Genomic Imprinting
Oogenesis
Spermatogenesis
Epigenetic differences result in differences in expression
DNA methylation
reversible chemical modification of the DNA
gene 1
gene 2
gene 1
gene 2
stop signs
gene 1
gene 2
gene 1
gene 2

18. Reciprocal heterozygotes are non-equivalent≠

19. Conflict over resources
make this better
inclusive fitness first

20. Asymmetries in relatedness
Maternal optimum
Paternal optimum
Growth factor expression level
Inclusive fitness
Fitness increases as more resources are acquired for self
Fitness decreases as cost to siblings becomes too great

21. Conflict over resources
Growth-enhancing locus
Unimprinted
gene
Cis-acting
maternal
modifiers
Maternal expression
Maternal optimum
Cis-acting
paternal
modifiers
Paternal optimum
more time explaining this one
maybe have things show up piece by piece
no imprinting first
Paternal expression

22. Conflict over resources
Growth-suppressing locus
Unimprinted
gene
Cis-acting
maternal
modifiers
Maternal expression
Paternal optimum
Cis-acting
paternal
modifiers
Maternal optimum
Paternal expression

23. 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 of gene expression
2p - fraction of mother’s offspring with the same father
Growth enhancer:

24. Population-genetic models
Two sibs, paternal imprinting
A - unimprinted allele
a - imprintable allele
a = A when maternally inherited
a -> (a) when paternally inherited
AA = 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 only one is imprinted:
e.g., AA & A(a)
Imprinted fitness: 1-s for A(a)
Unimprinted fitness: 1+t for AA

25. Population-genetic models
Parameters: allele frequencies, fitnesses, frequency of multiple paternity
Spencer, Feldman, and Clark 1998 Genetics

26. Population-genetic models
Two sibs, paternal imprinting
A - unimprinted allele
a - imprintable allele
a = A when maternally inherited
a -> (a) when paternally inherited
AA = 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 only one is imprinted:
e.g., AA & A(a)
Imprinted fitness: 1-s for A(a)
Unimprinted fitness: 1+t for AA
Monandrous females:
a invades A if u > s
a stable if u > t/2
Polyandrous females:
a invades A if s < 0

27. Predictions and contradictions
Game-theoretic
Imprinting requires multiple paternity (p < 1/2)
Allele favoring lower expression will be completely silenced
maternal silencing of growth enhancers
paternal silencing of growth suppressors
Population-genetic
Particular combinations of s, t, and u can produce stable polymorphisms
Multiple paternity is not required
Maternal silencing for growth enhancers is more likely, but paternal silencing can occur

28. Paternally silenced growth enhancer
Growth-enhancing locus
Unimprinted
gene
Reduced paternal
expression would
be favored from
these points
Cis-acting
maternal
modifiers
Maternal expression
Cis-acting
paternal
modifiers
Maternal optimum
Paternal optimum
more time explaining this one
maybe have things show up piece by piece
no imprinting first
Paternal expression

29. Key assumption
Game-theoretic models assume that the unimprinted expression level is at its optimum before the introduction of an imprinted allele
Is this assumption a good one?
Gene expression array analyses of population-level variation reveal a high level of variation
This implies a good opportunity for selection to find the optimum

30. Separation of timescales in the evolution of imprinting
Imprinting opens up a new dimension in strategy space
Unimprinted alleles are restricted to a subspace in the fitness landscape
If mutations that quantitatively change gene expression are much more common than those that give rise to imprinting, imprinting will always arise in the context of an optimized expression level

31. Take-home message
Choice of a particular modeling framework implies certain assumptions that can affect your interpretation of your results
When smart people doing reasonable things disagree, there is probably something interesting going on