1 Novel environments 2 ‘Novel’ genes, genotypes (via mutation, drift, inbreeding, gene flow,selection)3 Tradeoffs between opposing selective pressures (eg autoimmune vs infectious diseases)4 Extremes of adaptations (eg overgrowth, extreme male brain)5 Conflicts within and between species6 Constraints on optimization (evolutionary legacies)• Trait involves benefits to own reproduction, or to kin, that offset costs to phenotype (genes that increase reproduction spread even if they decrease health, happiness or longevity)8 Trait is not a disease but a beneficial protective response (eg cough,fever,pain,nausea,vomiting,anxiety,fatigue)

Human Adaptation - ad aptos: ‘good fit’ between trait and environment

-produced by natural selection-better than alternatives in immediate circumstances

How are health and disease related to human adaptations?

The BIG 8 can give rise to apparent maladaptations

Definitions and perspectives on adaptation (from Crespi 2000)

(1) Teleonomic - focus on functional design - how the trait or form of trait has been ‘designed’ by selection for function in some context

(2) Phylogenetic - infer origin of trait using phylogeny, infer ‘selective regime’ under which trait arose, test performance of trait in ancestral and current selective regimes. If trait arose under current selective regime, & exhibits higher performance than antecedent, then is called an adaptation; mostgenerally, this approach is the comparative method

(3) Population and quantitative genetic - relate allelic and genotypic variation to phenotypic variation and fitness variation. ‘Purifying’ selection and stabilizing selection are evidence of adaptation, positive and directional selection are evidence for adapting. Adaptive peak viewpoint is conceptually useful

Trait value

Fitness

Observe a Trait, Trait Variation (cognitive, emotional,behavioral,morphological, physiological,molecular)

What is its adaptive significance? -> does presence or form of trait or phenotype increase survival and reproduction of its bearers,and if so, how? -> does trait involve interactions between individuals, within or between species? Cooperation or conflict?

Information on adaptive significance is crucial to understanding both proximate and ultimate causesof the forms of traitsNOTE: adaptive significance is often conditionalon environmental variation

ALTERNATIVE HYPOTHESES

*(1) Adaptive (function optimal)Very close fit between trait and environment of trait

*(2) Adaptive compromiseTradeoff between opposing selective pressures - what are they? costs AND benefits present

*(3) Non-adaptive (neutral) byproduct of another trait, or other cause

*(4) Mal-adaptive

HOW DO WE TELL THE DIFFERENCE?

APPROACHES (1) Functional design

what does trait do? with what aspect of environment does it interact?

(2) Analysis of selection

measure genotype or phenotype, and fitness, andanalyze their relationship

(3) Phylogenetic and comparative analysis

analyze relationship between traits, or traits and environments, over evolutionary time, across species or across populations, in a phylogenetic context

METHODS OBSERVATION

What are processes and patterns in nature?Correlation vs causation: x,y, and zgiven x <-> y, causal relation is:x-> y or y-> x or z -> x and y

EXPERIMENTSPerturb the system, predict the outcome based on hypothesis under test, differentiate between correlation and causation - KO

MODELLINGMake assumptions, explore mathematical consequences

Components: (1) strategy set(2) optimization criterion (eg fitness)(3) maths for determining which ‘strategy’ is optimal under what circumstances

Combining the approaches and methods

(1) Functional design Observation, experiments, modelling: what aspect of environment does trait interact with, and how?

(2) Measuring selection and response to selectionObservation: how does trait covary with components of fitness?What is the form of selection? Is the trait evolving now?What is its genetic basis?

(3) Comparative, phylogenetic methodObservation: How have trait and environment changed over evolutionary time? Has the trait evolved in parallel with the environmental factor? Have two traits evolved in association with one another? Can do between species or between populations.

• EXAMPLE: more sperm competition should select for larger testes (and more sperm)

- Experimental evolution: often not practical

- Interspecific comparison: test whether traits are correlated across species

• Problem: related species may share the same traits due to shared ancestry = phylogenetic non-independence

• Result is that species cannot be taken as independent data points

Phylogenetic, comparative tests of evolutionary theories

Example

Degree of sperm competition

Tes

tes

size

AB

CD

E F

Plain correlation doesn’t mean much – if species D, E and F are closely related they could have evolved larger testes sizes only once

Independent contrasts

Trait 1 Contrast

Tra

it 2

Con

tras

t

51

62

62

95

Trait 1: (6-5=1)Trait 2: (2-1=1)contrast: (1,1)

Felsenstein 1985

Felsenstein 1985, 1988

Trait 1 Contrast

Tra

it 2

Con

tras

t

51

62

62

95

Trait 1: (9-6=3)Trait 2: (5-2=3)contrast: (3,3)

Independent contrasts

Trait 1 Contrast

Tra

it 2

Con

tras

t

51

62

62

95

5.51.5

7.53.5

Averageof

descendents

Trait 1: 7.5-5.5=2Trait 2: 3.5-1.5=2contrast: (2,2)

Independent contrasts

SOME CAUSES OF LACK OF ADAPTATION

(1) Evolutionarily-novel environments (mismatches!)e. g., moths at lights, humans with novel technology, candy bars

(2) Time lagse. g., fruit dispersal by extinct megafauna, rapid change in human environments, long time needed to fix advantageous mutations; LCT

(3) GeneticsLack of sufficient genetic variationHeterozygote advantage Linkage, pleiotropy

(4) Local, not global, optimization

Case study: laryngeal nerve

Laryngeal nerve anatomy

1. down the neck

2. behind the aorta3. up neck

4. to larynx

Is it adaptive?

For giraffes?

EXAMPLES OF ANALYSES OF ADAPTATION

Darwin’s finches Human brain size

Recognizing and demonstrating maladaption is challenging and it is best conducted by combining analyses of proximate mechanisms AND ultimate causes

Darwin’s finches

Beaks as functionally-designed ‘tools’ for food acquisition

Measuring selection on beak size

Phylogenetics of finches and their beaks

No comparative analyses done yet!

EXAMPLES

Darwin’s finches Human brain size (and shape)

FUNCTIONAL DESIGNMEASUREMENT OF SELECTIONCOMPARATIVE ANALYSIS

Facial perception

Affect recognition

Social judgement

Mentalizing

Gaze detection

FUNCTIONAL DESIGN OF THE BRAIN:

‘Social Brain’: Distributed, Integrated Neural System ‘for’ Acquiring and Processing Social Information

Funct IMAGINGLESIONSTMSNatural variation

SELECTION AND HERITABILITY:Human brain size increase:

Tripled in about 4 million yearsMainly in the neocortex

Selection on genes ‘for’ human brain sizeMicrocephaly genesASPM and MCPH1

Heritability of brain size is high

BENEFITS: BRAIN SIZE IS POSITIVELY CORRELATED WITH MEASURES OF ‘INTELLIGENCE’, AMONG PRIMATES and WITHIN HUMANS

Brain, 2006

Narr et al. Cerebral Cortex, 2007

p<0.01

Brain Behavior Evolution, 2007

p<0.01

EARLY LIFE-Malnutrition-Pathogens-Infectious diseases

Austria, Upper Paleolithic

Now

When and how has most natural selectiontaken place in humans?

AGE

%SV

Sandiford et al. 1997

Cvorovis et al. 2008

Wachs et al. 2006

Martin & Kubzansky 2005

Webb, Sellen et al. 2009

In humans, maternal ‘intelligence’ is positivelycorrelated with measures of child survivorship and health

Implications for public health?

COSTS

Brain is VERY LARGE and energeticallyCOSTLY to grow and maintain:

Is 3X larger than expected forprimate body size

Has 22X the metabolic rate of skeletal muscle

PHYLOGENETIC, COMPARATIVE ANALYSIS OF BRAIN FUNCTION

1996 2007

1 Novel environments 2 ‘Novel’ genes, genotypes (via mutation, drift, inbreeding, gene flow,selection)3 Tradeoffs between opposing selective pressures 4 Extremes of adaptations (eg overgrowth, extreme male brain)5 Conflicts within and between species6 Constraints on optimization (evolutionary legacies)7 Trait involves benefits to own reproduction, or to kin, that offset costs to phenotype (genes that increase reproduction spread even if they decrease health, happiness or longevity)8 Trait is not a disease but a beneficial protective response (eg cough,fever,pain,nausea,vomiting,anxiety,fatigue)

Human Adaptation - ad aptos: ‘good fit’ between trait and environment

-produced by natural selection-better than alternatives in immediate circumstances

How are health and disease related to human adaptations?

The BIG 8 can give rise to apparent maladaptations

TP53

Codon 72: Pro/Pro compared to Pro/Arg, Arg/Arg

Lower apoptotic potential, leading to Higher implantation failure (& lower reproduction)Higher cancer riskHigher overall survival (longevity)

Other polymorphic genes in TP53 pathway mediate same tradeoffs

Kang et al. 2009 PNAS; Corbo et al. 2012 PLoS ONE

Genes ultimately mediate medically-important tradeoffs I

Functional design? knockouts, molecular mechanismsSelection - at molecular levelComparative - within/among species variation

p53 is a nuclear phospho-protein which, in response to DNA damage, slows progression through the cell cycle and initiates apoptosis if damage is severe. Tumour-specific point mutations occur in many forms of human cancer with as many as 50% of cancers containing a p53 mutation. 20% of mutations are concentrated at 5 'hot-spot' codons.

APOE

E4 alleles, compared to E3 and E2

Better verbal, memory skills (especially when young)

Increased risk of schizophrenia and Alzheimer’s

Alexander et al 2007 Biol Psy; Chang et al. 2011 NeuromageJochemsen et al. 2012 Neurob. Aging

Genes ultimately mediate medically-important tradeoffs II

COMT

VAL158MET polymorphism

Mediates prefrontal, striatal dopamine levels

VAL - better cognitive flexibility, updating;worse cognitive stability

MET - worse cognitive flexibility, updating; better cognitive stability

Fallon et al. 2012 Cerebral Cortex

Genes ultimately mediate medically-important tradeoffs III

Combining the approaches and methods to recognize adaptation (e.g., health) and maladaptation (e. g. disease and its risk)

(1) Functional design Observation, experiments, modelling: what aspect of environment does trait interact with, and how?

(2) Measuring selection and response to selectionObservation: how does trait covary with components of fitness?What is the form of selection? Is the trait evolving now?What is its genetic basis?

(3) Comparative, phylogenetic methodObservation: how have trait and environment changed over evolutionary time? Has the trait evolved in parallel with the environmental factor? Have two traits evolved in association with one another? Can do between species or between populations.

Causes, effects and evolution of allelic variation: how to THINK about genes and genic variation, and their relation to disease

Inclusive fitness: how to THINK about situations whererelated individuals interact

Adaptive significance: how to THINK about variation in phenotypes - benefits and costs, tradeoffs, evolutionary history, relation to maladaptation/disease

NOW

How to THINK about patterns of evolutionary change across generations in genes and phenotypes -> phylogenetics, thehistory of biological entities