History of Nature vs Nurture

John Locke (1632 – 1704)

Individuals are born without built in mental content; they are ‘tabula rasa’. All knowledge
comes from experience. All behaviour traits formed by nurture.

Sir Francis Galton (1822 – 1911)

Studied relatives of eminent men (‘Hereditary Genius’ 1869). Family of eminent men were more
often eminent themselves, therefore, human cognitive abilities are heritable; nature.

Ivan Pavlov (1849 – 1936)

Pavlov response (1890) Conditioning - nurture.

John Watson (1878 – 1958)

‘The behaviorism manifest’ (1913); “Give me a dozen healthy infants, well-formed, and my own
specified world to bring them up in and I’ll guarantee to take any one at random and train him to
become any type of specialist I might select.”
Little baby Albert (1919) turning curiosity into fear using a ‘loud scary noise’. Nurture.

Skinner (1948)
‘Walden Twee’ – social science fiction; raising of children by ‘specialists’ in an aim to
create a peaceful world.

Sir Francis Galton introduced term Nature vs. Nurture

Suggested that the use of adopted individuals and twins would be a more sufficient way to study
this.

Wouter Buikhuisen (1933 -)

Interested in anti-social behavior; (1978) Might biological factors play a role in criminal
behavior? Society did not approve, subject was too controversial. Riots. Buikhuisen moved to
Spain, works in antique. Nature.

Thomas Bouchard (1937 -)

The Jim twins (1979) separated from birth, weird similarities (name (ex)wife, son and dog same
etc). Bouchard reunited about 100 separated MZ twin pairs, found striking similarities in
cognitive functioning, habits, interests, and personality. Nature.

Monozygotic twins - MZ
Genetically identical, originate from single egg and single sperm.

Dizygotic twins - DZ
Genetically same as siblings, originate from two different eggs and two different sperms.
 Frans de Waal; Evolutionary foundations of morality

Nature vs. nurture can be investigated trough twin studies and evidence for evolution of the
trait.

Central question: Are human specific (?) traits such as altruism, empathy, and morality
determined by nurture or nature?

Approach: Explore evidence for evolution of these traits.

TED talk; animals work together to ‘pull in food’ even if one just ate. Apes yawn when simulation
yawns. Apes comfort(console) each other. Ape throws back cucumber because other ape gets a
grape for completing the same task.
ABC news; no need for religion to separate right from wrong, morality existed before religion.

Answers
- The foundations of morality (fairness and compassion) are present in a wide range of species.
Morality appears to be an evolved characteristic (at least partly encoded in our genes).
- Because animals appear to posses the foundations of morality (and are not religious), religion
is not needed to explain the human trait of morality. Religion may be a (environmental/genetic)
factor that supports morality because religiosity is a frequently observed phenotype.
 Basic genetics I

The eukaryotic cell

- Plasma membrane wraps the cell and holds its contents together
- Nucleus container of genetic information
- Endoplasmic reticulum protein production
- Golgi apparatus protein modification and sorting
- Lysosome protein degradation
- Mitochondrion energy/ATP production
- Cytoskeleton shape, locomotion, strength, transport

Mitochondria are the powerhouses of the cell, they contain mitochondrial DNA, produce energy
(ATP) and are presumed to originate from a symbiosis of bacteria with early eukaryote cells.

Nucleotides
Structure:
Central sugar molecule
Base groups attached to the 1’ position
A - adenine
T - thymine
C - cytosine
G - guanine
OH (hydroxy) group attached to the 3’ position
Phosphate attached to the 5’ position

DNA polymers connect through their base groups;

Adenine always pairs with thymine through 2 hydrogen bonds
Cytosine always pairs with guanine through 3 hydrogen bonds

DNA strands run in opposite direction

5’ ----> 3’
3’ <---- 5’

DNA folds into a DNA helix due to hydrophobic and hydrophilic interactions.
DNA Replication
During cell division DNA doubles and is divided among cells

,,,,

Introduction to evolution
A species is a group of individuals that interbreed in nature and can produce fertile
offspring.

Charles Darwin
Species originated through a mechanism where variants of a single species (different
genotypes) were selected by natural selection (selection of genotypes by environment) to later
become new species.

Alleles are DNA variations of a gene. They modify the amount or structure of a single protein,
which has (observable) effects on one or more traits of the individual (enzyme activity, pigment
molecules in skin cells, color of species, adaption to environment)

Natural selection can be positive; enhancing survivability and increasing frequency, or negative;
decreasing survivability and decreasing frequency.

Support for Darwin’s evolution theory

Genetic
DNA is the carrier of information that is transmitted to offspring

Phylogenetic
The DNA sequence of terrestrial species is related

Palaeontology
Fossil evidence of transitional species have been found

Evolution theory proposes that prolonged natural selection of variants within a species
ultimately resulted in the formation of different species

The substrate for the evolutionary mechanism is DNA that accumulates random sequence
variation and is selected for at the level of the genome

Van Straalen; Darwin’s theory of evolution

Human genetics I
Why do people differ? Three sources of variation;

A genes
C shared or common environment
E unique environment and measurement error

Family studies
Family designs do not really distinguish between shared genes and shared environment

Adoption studies
Pitfalls;
- Correlation between adoption and biological parents
- Prenatal (in utero) environment
- Are adoption parents representative of the general population?

Twins reared apart design

Bouchard.

Twin design
Resemblance reflected in twin correlations. If rMZ > rDZ, genetic influences play a role in that
particular trait.

Monozygotic twins Dizygotic twins

100% shared genes 50% shared genes
100% shared environment 100% shared environment
0% unique environment 0% unique environment

Heritability is that part of the variation (for a given trait) that can be explained by genetic
variation

If you have twin correlations you can calculate the relative contributions of genetic variance (A)
and shared (C) and unique (E) environmental variance.

A = 2 * (rMZ – rDZ)
C = (2 * rDZ) - rMZ
E = 1 – (A + C)

If rDZ < ½ rMZ; A = rMZ

STROOP task – measuring attention (Inhibition/focusing/distraction)

Reaction time when:

1: pronouncing colors written in one color
2: pronouncing name of color of colored block
3: pronouncing colors written in different colors

Adoption, family and twin studies have a long history, starting with Francis Galton, continuing
till now. Each design has its strengths and weaknesses.

Twin studies are the workhorses of heritability studies. In the twin design, the resemblance
between MZ pairs (presented as within pair correlation) is compared to the resemblance
between DZ pairs for a given trait.

When MZ correlation > DZ correlation: genetic influences explain (partly) individual differences
for that particular trait.
 Use MATCH yourself. http://match.ctglab.nl/#/home

You should be able to use:

Analysis-specific traits
Analysis-multiple traits

You should understand the concept of:

Twin correlations
Least square estimates
Reported ACE

Human genetics II

Dynamics in genetic studies

Development over time
The influence of genetic and environmental variation on the variation of a certain
trait can change over time. IQ changes from 30% genes and 70% environment to
80% genes and 20% environment during a lifetime.

Gene-environment correlation (role of genetics in exposure to environments)

Passive: Your parents create an environment that fits with their (and thus your)
genes
Evocative (reactive): Your behavior (partly determined by genes) evoke certain
responses from other people
Active: You seek or create environments that fit your genes

If musical ability is heritable, musically gifted children are likely to have

musically gifted parents who provide them with both genes and an environment
conducive to the development of musical ability (passive). Musically talented
children may also be picked out at school and given special opportunities
(evocative). Even if no one does anything about their musical talent, gifted
children might seek out their own musical environments by selecting musical
friends or otherwise creating musical experiences (active).

3 methods to detect correlations;

- Comparing correlations between environmental measures and traits in non-
adoptive and adoptive families (passive)
- Comparing correlations between birthparents’ traits and adoptive families’
environment (evocative and active)
- Multivariate genetic analysis of the correlation between an environmental
measure and a trait (passive, evocative or active)

Gene-environment interaction (genetic sensitivity or susceptibility to environments)

The effect of the environment on a phenotype depends on genotype (I). The effect of the
genotype on a phenotype depends on the environment (II):
(I) The effect of a polymorphism in the MAOA gene on antisocial behavior
depends on childhood maltreatment
(II) SES on IQ

Research… p 120
Linkage study design (family data)

Linkage studies affected sib-pair (ASP) method

Case control design: individuals with a disease and healthy individuals

Underlying concept:
- At a single genetic locus an offspring can receive 2 parental alleles (one from the
mother, one from the father)
- Pairs of siblings can share 2, 1, or 0 alleles transmitted from their parents
- Prior probabilities (what you expect): Z2=0.25, Z1=0.5, and Z0=0.25
- Linkage (‘shared disease related alleles’) will cause a shift in this distribution among
affected siblings

1 Marker data for a large number of ASPs

2 For every DNA marker determine the % of alleles shared between each pair of affected siblings

>>50% sharing for a particular DNA marker: DNA marker is closely linked to a susceptibility
gene present in both siblings!

Allele sharing can be identical by descent (IBD) (inherited by the same parent) or identical by
state (IBS) (inherited by a different parent)

If parents are not available for genotyping, one of the parents is homozygous or when the
parents are heterozygous for the same marker alleles, IBD might not be possible with 100%
accuracy.

Conducting a sib-pair study

- Collect families with at least 2 affected siblings
- Perform a genome-wide scan with regularly spaced polymorphic markers
- Statistical analysis
Look for excess IBD (!) allele sharing
Test deviation from Z2=0.25, Z1=0.5, and Z0=0.25 for each marker

Linkage for a quantitative trait

Linkage for quantitative trait scores: individuals with a score on a continuous trait (e.g., IQ)

The whole genome is searched using genetic markers along the genome
- Linkage (‘shared trait related alleles’) will cause a shift in the expected distribution of
alleles among siblings with e.g., a similar IQ score
- A significant linkage signal, expressed in a “lod” (log-odds) score, shows up as a peak
- This peak lies in a genomic region that may harbor 100-300 genes
- Large samples needed

Disadvantages linkage studies

- Large family samples needed (with affected siblings for case control design)
- Findings regarding regions in the genome, no specific locus or gene yet

Follow up: candidate gene study (hypothesis driven)

Ideal candidate genes:

1. Under a linkage peak
2. Biologically plausible
CHRM2 gene and intelligence (2006) only 1 confirmative study in 2007

Disadvantages candidate gene studies

- Focus on one gene might not be biologically plausible in itself (only one gene having a great
effect on IQ?)
- Replication often failed
- Large samples needed, however, not necessarily family samples

Human complex traits are ‘polygenetic’: many genes with each a very small effect play a role
Associated genes can be anywhere in the genome

Genome Wide Association Studies GWAS (hypothesis free)

Rapid advances in genotyping technologies last 10 years: genetic association can now be done
on a genome wide scale (GWA), SNP by SNP..

Difficult to find significant effects (Manhattan plot)

Disadvantages GWAS
- Focus on single SNPs might not be biologically plausible in itself (only one SNP having a great
effect on IQ?)
- Replication often failed
- Large (VERY large!) samples needed, however, not necessarily family samples. From large twin
registers to large genetic samples [‘consortia’]!
- Expensive! (± E350 per individual/2014)
- Explained variance is low: ~0.01 to 1%

Epigenetics
Epigenetics (“above genetics”)
The study of molecular mechanisms that influence the activity of gene expression and that are
transmitted across cell division.

Epigenetic mechanisms have 2 major functions

- Fold the entire human genome into each cell nucleus
- Regulate gene expression