1. Midterm 1 Results Frequency Mean = 80 Standard Deviation = 12
Highest score = 100
Lowest score = 47
Score

2. Constraints on Natural Selection

3. Natural Selection does not always proceed in the expected direction, because several forces could interfere with the action of Natural Selection

4. Constraints on Natural Selection
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Constraints on Natural Selection
Phylogenetic Inertia (Historical Constraints): can only build on what is there (hard to make wings without appendages)
Physical Constraints (anatomical constraints): a structural or anatomical feature could prevent a modification of a trait (brain might not be able to grow if body cannot grow)

5. Physical Constraint Developmental constraint Constraint in Body Plan
If body size increases, brain size has to increase
If a larger eye evolves, need a bigger socket (the socket itself is not the target of selection)
Analogy: the Spandrels of San Marco

6. San Marco Cathedral, Venice
Gould & Lewontin:
The metaphor:
The spandrels of San Marco
San Marco Cathedral, Venice

7. San Marco Cathedral, Venice
Gould & Lewontin on Physical Constraint:
The spandrels of San Marco might not have been created for a reason, but might simply be a by product due to the creation of arches
San Marco Cathedral, Venice

8. Constraints on Natural Selection
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Constraints on Natural Selection
Genetic Constraints
Genetic Variation: Selection can only act on existing genetic variation; if there is not variation, there can be no selection
Pleiotropy: one gene might affect more than one trait. So if you alter a gene, it could have multiple effects. So you might not be able to alter that gene
Sometimes Antagonistic Pleiotropy could lead to evolutionary trade- offs, but there are other causes of trade-offs, as well (not all evolutionary trade-offs are due to Antagonistic Pleiotropy)
Linkage: alleles close together on a chromosome could share a fate just do to physical proximity and undergo selection and be inherited as a unit
Genetic Drift will interfere with the action of Natural Selection in small populations

9. Pleiotropy: when a gene affects many traits or functions
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Pleiotropy: when a gene affects many traits or functions
Difficult to select on a gene that affects multiple traits: Because, changing the gene could negatively affect the other traits
Conversely, a seemingly unbeneficial trait might get selected for because the gene that codes for it also enhances fitness, due to beneficial impacts on another trait
Antagonistic Pleiotropy could lead to evolutionary tradeoffs
Proceedings: Biological Sciences
ISSN: (Paper) (Online)
Issue: Volume 271, Number 1554 / November 07, 2004
Pages:
Abstract:
The Darwinian paradox of male homosexuality in humans is examined, i.e. if male homosexuality has a genetic component and homosexuals reproduce less than heterosexuals, then why is this trait maintained in the population? In a sample of 98 homosexual and 100 heterosexual men and their relatives (a total of over 4600 individuals), we found that female maternal relatives of homosexuals have higher fecundity than female maternal relatives of heterosexuals and that this difference is not found in female paternal relatives. The study confirms previous reports, in particular that homosexuals have more maternal than paternal male homosexual relatives, that homosexual males are more often later-born than first-born and that they have more older brothers than older sisters. We discuss the findings and their implications for current research on male homosexuality.

10. Antagonistic Pleiotropy: when one gene controls for more than one trait where at least one of these traits is beneficial to the organism's fitness and at least one is detrimental to the organism's fitness.
Pawlowski, B., Dunbar, R. I. M. and Lipowicz, A.
2000 Evolutionary fitness: Tall men have more reproductive success. Nature 403: 156.

11. Antagonist pleiotropy can lead to trade offs
Mutations at single genes that cause high estrogen levels could increase fertility (trait 1), but also cause cell proliferation in breast and ovarian tissue (trait 2) leading to cancer (estrogen has many targets in the body, and many consequences)
In HIV, slow and careful reverse transcriptase confers AZT resistance (trait 1), but slow growth rate (trait 2)
Sickle Cell Anemia - heterozygote for the Hb locus (HgbS) leads to resistance to malaria (removal of parasite from blood, trait 1) but lower oxygen carrying capacity (trait 2)

12. Not all Evolutionary Tradeoffs are due to Antagonistic Pleiotropy
Evolutionary tradeoffs could arise between traits encoded by multiple genes
With limited resources, there would be evolutionary tradeoffs between growth and reproduction
There could be tradeoffs between lifespan and reproduction

13. Linkage
Definition: The tendency for certain alleles to be inherited together due to their physical proximity on the chromosome
Human linkage map
Phenotypic evolution could arise due to linkage (≠adaptation): Genes might experience an evolutionary shift because another gene closely linked on the chromosome is under selection (selective sweep)
This is a genetic mechanism of evolutionary change that is NOT adaptive

14. Linkage
Definition: The tendency for certain alleles to be inherited together due to their physical proximity on the chromosome
Human linkage map
Consequence: Selection at a locus (gene) might cause selection at many other genes closely linked on a chromosome, even if there is no reason for those other genes to evolve

15. Genetic Drift and Natural Selection
Because of the randomness introduced by Genetic Drift, Natural Selection is less efficient when there is genetic drift
Thus, Natural Selection is more efficient in larger populations, and less effective in smaller populations

16. Selection acts only on genes that are expressed
Remember that selection acts on the phenotype… the traits that are expressed, given the genotype

17. Adaptation vs
Plasticity

18. Conceptual Confusions
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Conceptual Confusions
Trait variation is often assumed to be due to Adaptation, when the differences might be due to Phenotypic Plasticity or nonadaptive genetic causes

19. The Problem:
People often wish to jump to the conclusion that a trait change they see is the result of adaptation (Natural Selection)
However, that is not always the case. There are other mechanisms that could cause phenotypic variation
This is what Stephen Jay Gould called the “Adaptationist Paradigm”

20. The Problem:
Adaptations are ubiquitous, but demonstrating that a particular trait is an adaptation is not always easy

21. The Problem
Need to distinguish genetically-based differences from plastic (environmentally-induced) differences
Need to distinguish adaptive genetically-based differences (due to Natural Selection) from nonadaptive genetically-based differences (due to other forces)

22. Example in which adaptation and plasticity were poorly distinguished:
The Bell Curve, 1994 by Murray and Hernstein
Murray and Hernstein used IQ score differences to make the argument that African-Americans are genetically (and evolutionarily) less intelligent than European and Asian-Americans
Scientifically, there are key flaws in their argument

23. Their argument has key flaws:
(1) Not account for environmental effects on IQ
intelligence is known to be a plastic trait, affected by pollution (lead), nutrition, cognitive stimulation, etc.
(2) Correlation is associative, not causative
If IQ and “race” are correlated, it does not mean that race is responsible for IQ
A third factor could be correlated with both race and IQ that might actually be the underlying cause

24. Fischer reanalyzed Murray and Hernstein’s data and found that socio-economic status was a stronger determinant of IQ scores than race, even in their examples (Inequality by Design: Cracking The `Bell Curve' Myth)
Rigorous tests are required to determine whether or not IQ is genetically based in human populations (later in the lecture)

25. Components of Phenotypic Variation
Quantitative traits are controlled by many loci, many of which with small effects. For quantitative traits, we depict the sources of variation as follows:
Phenotypic variation is a result of variation that is due to genetic effects (VG), variation due to environmental factors (VE) and their interaction.
VP = VG + VE + VGxE
So, some of the variation could be due to genetic causes, but some might be induced by the environment (as a result of gene expression).

26. In other words: VP = VG + VE + V(GxE)
VG: Genetically based (and heritable) differences, resulting from natural selection (adaptation) or other genetic factors (genetic drift, etc)
VE: Differences that are inducible by the environment by a given genotype (acclimation, phenotypic plasticity)

27. AND Not All Heritable Variation is due to Adaptation (Natural Selection)!!!
Phenotypic change and variation could have other causes:
Plasiticity: Changes that are not due to genetic changes, but due to changes in gene expression: Phenotypic Plasticity (including nonheritable epigenetic modifications)
Changes that are Genetic, but NOT adaptive:
Genetic Drift: random chance
Linkage and Genetic Hitchhiking: Genetic changes that occur because the gene was right next to another gene on a chromosome that was under selection
Physical or structural Constraints (like the Spandrels)

28. Critique of the “Adaptationist Programme” Gould & Lewontin 1979
Critique of the “Adaptationist Programme” Gould & Lewontin The Spandrels of San Marco and the Panglossian Paradigm: A Critique of the Adaptationist Programme.
One of the most important papers in Evolutionary Biology
They critique the “Adaptationist” and “Panglossian Programme” that assumes that a phenotypic change is the result of adaptation
Gould & Lewontin point out that not all phenotypic variation or phenotypic evolution is the result of adaptation

29. San Marco Cathedral, Venice
Gould & Lewontin:
The spandrels of San Marco
San Marco Cathedral, Venice

30. San Marco Cathedral, Venice
Gould & Lewontin on Physical Constraint:
The spandrels of San Marco might not have been created for a reason, but might simply be a by product due to the creation of arches
San Marco Cathedral, Venice

31. Adaptation Requires Natural Selection
Requires polymorphism in a population
MUST have an effect on Fitness
Is a frequency (%) change in a population
There must be a Selective Force

32. How can you tell if a trait evolved as a result of adaptation?
(1) The trait must be heritable
(2) The differences between populations are genetically based differences rather than inducible differences (plasticity)
(3) The trait has fitness consequences (promotes survival, performance, and number of offspring)
(If a trait evolved due to genetic drift, linkage or pleiotropy, the change is genetic, but may confer no fitness advantage)

34. Phenotypic Plasticity
Definition:
Differences in phenotype that a genotype exhibits across a range of environments
Some traits with a plastic component: intelligence, height, temperature tolerance, salinity tolerance, muscle mass…

35. Acclimation (≠ Adaptation)
1) Result of Phenotypic Plasticity
2) Not heritable
3) Short term or developmental response within a single generation
4) Arises through differential gene expression or other regulatory mechanism rather than natural selection

36. Nature (genetics) vs Nurture (environment)
Both environment and genetics affect many traits, but need to experimentally or statistically separate these factors
How?
Example: Common-garden experiment
Having appropriate controls
Statistically assessing the effect of environment

37. This is a general problem
This type of problem is a factor in all studies that attempt to associate a gene with a trait
You need to account for the effects of environment
For example, problems arise when different labs attempt to associate a gene with a disease using laboratory mice that have been reared under different conditions

38. Types of Plasticity Short-term reversible Development acclimation:
generally irreversible
Genotype --> Development --> Phenotype
Within normal tolerance range
In response to Stress

39. Plasticity can be depicted graphically as a Reaction Norm
Response
Environment
Reaction Norm: the function which describes the plastic response

40. Response
Environment
In the case of plasticity, the different phenotypes in different environments are NOT the result of Adaptation…
The Genotype(s) in the environments are NOT changing
The differences between them are due to differences in response (such as gene expression) in different environments

41. Dodson, SI. 1989. Predator induced reaction norms
Dodson, SI Predator induced reaction norms. BioScience 39:447–452

42. Predator induced formation of helmets in Daphnia
Hebert and Grewe, 1985

43. Genotype x Environment Interaction (optional)
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The next 4 slides are optional because of lack of time
Genotype x Environment Interaction (optional)
VP = VG + VE + V(GxE)  this last interaction term
Changes in rank or level of performance among genotypes when tested in different environments
Reveals genetic variation for plasticity
Could reflect tradeoffs between fitness of different genotypes in different environments

44. Trade-offs in different environments
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When lines cross, the implication is that different environments will select for different phenotypes
Response
Environment
Trade-offs in different environments

45. Size big small hot cold Temperature
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Select for this reaction norm in cold environments
big
Size
small
Select for this reaction norm in hot environments
cold
hot
Temperature
Could get selection for different reaction norms (different plasticity) in different environments

46. 4/26/2017
Genetic variation for plasticity can be determined by examining the significance of the interaction term from an Analysis of Variance (ANOVA)
Genetic Variation for Plasticity
No Genetic Variation for Plasticity
Response
Environment
Environment

47. Example: Human IQ Data
Data: Many studies use survey data on human populations in the US (not a common-garden experiment, where environment is held constant)
Did not statistically account for differences in environment
A correlation is associative, and not necessarily causative

48. Problems with data and statistical analysis:
Several reanalyses have found that socio-economic status (and historical factors) was a stronger determinant of IQ scores than race.
Socio-economic status could reflect nutrition, access to education, etc.

49. Impact of environment must be accounted for:
There is an IQ gap between blacks and whites in America, Japanese and Koreans in Japan, Ashkenazi and Sephardic Jews in Israel, and Protestants and Catholics in Northern Ireland. As economic conditions improve for the subordinated groups, the gaps are reduced
A common-garden experiment has never been performed on humans with respect to IQ scores to determine actual genetic differences with environmental effects removed
Do not know of any study of IQ that has effectively controlled for socio-economic differences

50. Most Importantly,
Must distinguish (1) genetically based differences from phenotypic plasticity AND (2) genetic differences due to adaptations (natural selection) vs other causes of genetic differences (drift, just different mutations arising in diff populations, etc.
Many experiments fail to do this
Examples: drug response, hormone replacement therapy

51. How to distinguish between genetically based traits vs
How to distinguish between genetically based traits vs. phenotypic plasticity?
Animal Model Analyses: Determine how much of a trait is due to additive, dominance, genetic variance etc (quantitative genetic methods) – not cover here
Common-garden experiment: rear different populations in a common environment to remove the effects of environmental plasticity, and determine how much variation is remaining (and due to genetic effects).
Molecular Genetic Approaches: transgenic or gene knockout studies, to determine the impacts of particular genes on a trait

52. If the phenotypic change is genetically based, How to detect if the change was due to selection?
Selection in the Wild: Look at selection response in nature (R= h2S, breeder’s equation)
Selection Experiments (Experimental Evolution): Impose selection on a population, then examine evolutionary shift
Genetic Signatures of Selection: Look for genetic signatures of natural selection in the DNA sequences

53. Is the trait change genetically based?
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Is the trait change genetically based?

54. What is a common-garden Experiment?
An Experiment in which individuals from different populations or species are reared under identical conditions (can be over a range of conditions)
Remove differences due to environmental plasticity

55. Different Populations
Example:
Different Populations
A saltwater population and a freshwater population of a small crustacean (copepod) show differences in salinity tolerance.
Are the differences due to simply being reared at different salinities, or are the differences due to genetically based differences?
And three separate experiments were performed where the parentals were reared at a common salinity for 0, 2, and 5 generations prior to experimentation
In this case 0 generations at 5 PSU, meaning that they were reared at their native salinities

56. Different Populations
Common Garden Experiment
Different Populations
Rear under common conditions
To determine the differences
when the environment is held constant
And three separate experiments were performed where the parentals were reared at a common salinity for 0, 2, and 5 generations prior to experimentation
In this case 0 generations at 5 PSU, meaning that they were reared at their native salinities

57. Different Populations
Common Garden Experiment
If the populations still differ under common-garden conditions, the differences are genetically based.
But are these genetic differences the result of adaptation? (or some other genetic cause)
Different Populations
And three separate experiments were performed where the parentals were reared at a common salinity for 0, 2, and 5 generations prior to experimentation
In this case 0 generations at 5 PSU, meaning that they were reared at their native salinities

58. Molecular genetic approaches to determine the genetic basis of a trait
Is that gene causing the trait?
Transgenics, gene knockout studies, CRISPR gene editing, RNAi, etc.
Generally use model systems, such as mice, fruit flies, C. elegans, etc.

59. 4/26/2017
Detecting Selection

60. Laboratory Selection Experiments
But is salinity really the factor causing the evolutionary physiological change?
Perform selection experiments to test whether the evolutionary change happens in response to salinity alone.
But then the question is, salinity really the factor that caused the evolutionary change?… many factors might change during saline to freshwater invasions in the wild, such as food, pH, temperature fluctuations, etc.
To address these questions, we performed selection experiments to test whether the evolutionary response could take place due to salinity alone
We took the ancestral saline populations, and imposed selection for freshwater tolerance across 12 generations

61. Selection in the Lab saline ancestors
Control
Selection in the Lab
Selection for several generations
Take the saline population and then imposed selection for freshwater tolerance
Compare the populations before and after selection
Do the selection lines show the same evolutionary shift to fresh water as the wild population?
ancestor
freshwater selected lines 5 5 5
So, we performed selection experiments and produced artificial freshwater populations.
We took saline ancestral populations and brought them down in salinity and selected for freshwater tolerance over 7 generations and then maintained them at fresh water for an additional 5 generations. We did this twice from each saltwater ancestral population. And we did this from multiple saltwater populations (St. Lawrence and Gulf).
We also maintained a control at high salinity.
reared at compromised salinity to remove effects of acclimation
We then the ancestral population with freshwater selected lines, and measured enzyme activity across salinities.
acclimate at same salinity 5 15
Common garden experiment at the end of the selection

62. Detecting signatures of selection in DNA sequences
So, how does one detect Natural Selection in a population?
Many types of tests: use signatures of Linkage Disequlibrium, reduced variation (Selective Sweep), genetic deviation (Phi- ST)
The challenge is distinguishing natural selection from signatures of Genetic Drift

63. Codon Bias In the case of amino acids
Mutations in Position 1, 2 lead to Amino Acid change
Mutations in Position 3 often don’t matter

64. > 1 Simplest Test: Ka/Ks Test Nonsynonymous substitution rate Ka
Synonymous substitution rate Ks
Need coding sequence (sequence that codes proteins)
Ks is used here as the “control”, proxy for neutral evolution
A greater rate of nonsynonymous substitutions (Ka) than synonymous (Ks) is used as an indication of selection (Ka/Ks >1)
Substitution rate: out of all the possible number of mutations, how many fixed
> 1

65. > 1 Ka/Ks Test Nonsynonymous substitution rate Ka
Synonymous substitution rate Ks
In the absence of selection, you’d expect Ks = Ka, and for Ka/Ks = 1
A greater rate of nonsynonymous substitutions (Ka) than synonymous (Ks) is used as an indication of positive selection (Ka/Ks >1)
If Ks > Ka, or Ka/Ks < 1, that would suggest purifying selection, that selection might be preserving amino acid composition
> 1

66. Examples: Adaptation or not?
A plant grows taller to obtain more sunlight
Weeds in cornfields (corn is tall) are on average taller than weeds of the same species in soybean fields in order to obtain more sunlight

67. Examples: Adaptation or not?
A plant grows taller to obtain more sunlight
Plasticity
Weeds in cornfields (corn is tall) are on average taller than weeds of the same species in soybean fields in order to obtain more sunlight
Not enough information

68. Examples: Adaptation or not?
Weeds in a cornfield have been found to grow taller than those in soybean fields when both populations are reared in common-garden conditions
Taller weeds in the cornfields survive and a greater rate and leave more offspring
Weeds in a cornfield have been found to grow taller than those in soybean fields when both populations are reared in common-garden conditions : There are genetic differences.. But are they adaptive?
The trait must have fitness consequences

69. Examples: Adaptation or not?
Weeds in a cornfield have been found to grow taller than those in soybean fields when both populations are reared in common-garden conditions
They are genetically different, but not know for sure if it is adaptation (could be linkage, genetic drift)
Taller weeds in the cornfields survive and a greater rate and leave more offspring
Very like to be Adaptation
Weeds in a cornfield have been found to grow taller than those in soybean fields when both populations are reared in common-garden conditions : There are genetic differences.. But are they adaptive?
The trait must have fitness consequences