EVOLUTION: Lecture 3

The integration of Darwinism and Genetics:

the Rise of the Modern Synthesis

Robin Allaby
 Aims

• To look at the reaction to Darwin’s theory

• To be aware of some of the other theories of the day
• To understand some of the basic population processes that occur without the action of Natural Selection

Objectives
To examine:
• HWE
• Random Genetic Drift
• Population structure
• Inbreeding and outbreeding
• Founder effects and Bottlenecks
What did Darwin Achieve?

Darwin stated his principal goals were:

• to show species were not separately created

• Natural Selection was the chief agent of change

 Reactions to Darwinism: negative
• Fleeming Jenkin 1867 – the glass sphere simile: domesticates a poor
example for evolution if they are just deviations from the norm.
• St George Mivart 1871 – the unviability of incipient stages: the forms that
would occur on the formation of complex organs would be unviable. On the
Genesis of Species.

Mivart Jenkin
 Reactions to Darwin: positive

• Ernst Haeckel (1866) adopted Darwinism,

as well as Lamarckism and a structuralist
viewpoint!
- biogenetic law (ontogeny reflects
phylogeny)
- also coined terms ecology and
heterochrony, among others
The three alternatives to Darwinism
Darwin’s variation that Natural Selection worked on was small, undirected and copious.
These popular theories of the day all challenged that nature of variation, and therefore the
raw material of Natural Selection.

• Lamarckism
- functionalist

• Saltation
- structuralist

• Orthogenesis
- structuralist
 Lamarckism

Jean Baptiste-Lamarck

• variation was directed

• soft inheritance of acquired characters

• a mechanism of adaptation (functionalist)

• very popular, but fell out of favour with the rise of

genetics (hard particulate inheritance)…..in the West at
least.

• more recently, bacteria have been caught doing quite

Lamarckian things………

• epigenesis also can look a bit Lamarckian today

 Orthogenesis
• coined by William Haacke (1893)

• a formalist approach to explain embryological

development – means ‘straight line’

• an extension of the tradition of Goethe and Saint-Hilaire,

system of archetypes (Plato)
Gryphaea obliquata (devil’s toenail)
• evolution proceeds along defined and restricted
pathways because of interior (invisible) factors limit and
bias variation into specific channels

• variation therefore emphatically directional for structural

reasons

• species may be doomed to extinction in this theory e.g.

overcoiling of Gryphaea

Trueman (1922) Geol. Mag. 49:256-268

 Saltation: 1 Francis Galton 1869
Darwin’s firmly believed the variations that Natural Selection worked upon had to be small,
in keeping with Lyell’s uniformitarianism. The danger of large ‘mutations’ to his theory, was
that the mutations would become the agent of change, rather than selection building up
differences.

• Galton was Darwin’s cousin

• A firm believer in Natural Selection

• He did not accept that variations HAD to be small, and

that larger ones would be more effectively selected
• put forward a polyhedron simile to describe evolutionary
change flipping between stable states (1869, Hereditary
Genius)
• coined eugenics

Francis Galton
 Saltation: 2 William Bateson 1894
Bateson set his non-Darwnian formalist views in Materials for the Study of Variation (1894)

• environmental variation is continuous

• species are discontinuous – but they should be continuous to reflect

the environment that selects them
• therefore change is discontinuous

• set about cataloging variation

• recognized the meristematic nature of variation e.g. segment

number, not necessarily better or worse forms
• coined ‘genetics’
William Bateson
 Saltation 3: Hugo de Vries
• De Vries was also a firm believer in Natural Selection
and supporter of Darwin
• BUT believed larger ‘mutations’ were selected for and
responsible for speciation

• Mutation Theory 1909 – based on Oenothera, became

very successful
• rediscovered Mendel’s laws and established the
‘particulate’ nature of inheritance – taken as evidence
that variation occurs in large jumps
Hugo de Vries

Oenothera lamarckiana, a most

unfortunate choice of study
organism

Gregor Mendel, 1865, hijacked by the saltation movement

 Halfway summary
• Darwin very effectively convinced the world that life is all part of one system that is related by
descent, ultimately from a single species.

• Darwin’s mechanism was largely not accepted in his lifetime, his strict adherence to small changes
was favoured less than large (saltatory) mutations. Larger mutations are more associated with the
formalist tradition.

• The rediscovery of Mendel’s genetics was taken as support for a particulate form of inheritance
that was saltatory. This largely because of the choice of organism by de Vries.

• This is not a subject of absolutes; the debate was (and is) about which mechanism is primary in
evolution.

• Some criticisms of Darwinism in the day which were answered in principal, are still around today.

• Most, if not all of the lines of thinking about evolution from this time are still around in various
forms.
 Particulate inheritance becomes
mathematical
Mendel’s (and de Vries’s) laws of particulate inheritance had
some problems:
- the classic 3:1 ratio is almost never observed in nature
- Reginald Punnet (of the Punnet square) wanted to be
able to explain why it is that dominant alleles do not simply
become fixed in a population
- Punnet introduced the problem to Godfrey H Hardy
(whilst playing cricket)

Punnet Bateson

Punnet square
 The Hardy principle, and Hardy-Weinberg
Equilibria 1908
Hardy showed that the proportion of the dominant (p) and recessive (q) alleles
in a population need to be considered.

• Can calculate the expected genotype proportions

• The resultant proportions show that p and q do not change from generation to generation,
answering Punnet’s question
G.H. Hardy
• demonstrates that variation is preserved under particulate inheritance

• This system is used as a null basis in evolutionary studies – it shows what you expect to see in
genotype frequencies when evolution is NOT occurring.

• It is actually a simplification of a more complex mathematical description

(p) (q)

W. Weinberg, published 6 (p) (p2) (pq)

months earlier and more
comprehensively, but in
German so Hardy got the
(q) (pq) (q2)
credit, that’s science!
 Hardy-Weinberg Equilibria
p is the population proportion of allele B
q is the population proportion of allele b

In a 2 allele system,
p+q=1

The probabilities of picking alleles in the next generation can be summarized as a binomial expansion:

(p + q) x (p + q) = 1 (simply another way of expressing the Punnet square)

so (p + q)2 = 1 (note that a 3 allele system is simply (p + q + r)2 = 1, and so on)

p + 2pq + q = 1
2 2

So, if p is 0.3, q must be 0.7, therefore:

p2 (ie BB) is 0.09
2pq (ie Bb) is 0.42
q2 (ie bb) is 0.49
1
So the values of p and q are unchanged

Why is this useful?

Suppose you measured p and q in a population (to be 0.3 and 0.7)
But you found that the proportion of heterozygotes (Bb) was only 0.2
This formula tells you that something odd is going on - evolution
could be in action.
The Modern Synthesis

• Phase 1 The fusion of Mendelism and Darwinism

(Fisher, Haldane, Wright, Huxley)
• Phase 2 The linking of subdisciplines of
biology(Dobzhansky, Mayr, Simpson, White, Rensch,
Stebbins)
First strand of the Modern Synthesis: RA
Fisher
• Genetical Theory of Evolution (1930) – recaptured Mendelism from the
saltationists, strictly Natural Selection
• Darwinism requires a particulate inheritance to work: blending inheritance
(Darwin) would require an enormous amount of mutational input to fuel change,
so much so it would have to be internally driven
• large mutations are likely to be deleterious, therefore it is more likely that small
mutations would be subject to positive selection (see graph below)
• the rate of increase in fitness in any organism at any time is equal to its genetic
variance in fitness at that time
• also had a thing for eugenics

R.A. Fisher
 Second strand of the Modern Synthesis:
J.B.S. Haldane
• The Causes of Evolution (1932)

•Introduced pluralism to the Modern Synthesis: Natural Selection

not the only agent of change
• Not all changes had to be small, in his theory, but once occurred
would be subject to Natural Selection – saltational flavour
• Disagreed that mutations occurred in ‘every direction’ – most
mutations lead to a loss of complexity (function) – orthogenetic
flavour.
• Many differentia of species have no adaptive significance
• Palaeontological record may be biased because there is more
representation of species that have large numbers, therefore more
likely to be subject to the dynamics described by Fisher. Smaller
species would be more subject to dynamics described by Wright.

J.B.S. Haldane
Third strand of the Modern Synthesis: J.S.
Huxley
• Evolution, The Modern Synthesis (1942)

• Coined the term ‘Modern Synthesis’ to collect the work of the mathematical generation of
evolutionists under one umbrella

• Had a similar ‘pluralist’ viewpoint to Haldane ie causes of evolution wider than just Natural Selection

• some significance of the work of Wright acknowledged, although as with Fisher and Haldane, Natural
Selection was proposed as the major force.
The fourth strand of the Modern Synthesis: S.
Wright
• Evolution in Mendelian Populations (1931) Genetics 16:97-159

• Formed much of the basis of modern population genetics

• Identified random genetic drift as an important agent of change in small

populations – a new ‘force’ in evolution which received little credence at the
time
• coined the concept of adaptive landscapes (see shifting balance theory
later)

• Was an outsider, often shunned by the others of the neo-Darwinist

community because too much importance was laid on drift instead of
selection

Sewall Wright
 The second phase of the Modern Synthesis:
integration with the rest of biology

• Initiated by Dobzhansky Genetics and the Origin of Species (1937)

• Ernst Mayr (systematics) Systematics and the Origin of Species

• George G Simpson (palaeontology) The Tempo and Mode of Evolution

(1944)

• Michael JD White (cytology) Animal Cytology and Evolution (1945)

• Bernard Rensch (morphology) Evolution above the species level (1947)

• G Ledyard Stebbins (botany) Variation and evolution in plants (1950)

Theodosius Dobzhansky
‘Nothing in biology makes sense except in the light of evolution’ Dobzhansky 1973
 Summary of neo-Darwinism

• Hereditary variation of ‘continuous characters’ is

due to particulate (mendelian) genes.

• Even small differences in reproductive fitness can be

sufficient to bring about evolutionary change
observed in the fossil record
• selection can maintain genetic variation in a
population

• Natural Selection is one among several mechanisms

of evolutionary change

• Not all evolutionary change is adaptive, although it

was considered the dominant force
 Genes
• Mendel established a particulate form of inheritance which ‘genes’ underlie, but did not use the term. The alternative was
‘blending’ inheritance.
• Darwin used the term ‘gemmule’ to describe microscopic units of inheritance, and ‘pangenesis’ to describe his (flawed)
mechanism of inheritance (1868)
• De Vries coined the term ‘pangene’ (1889) as a saltatory unit of inheritance from pangenesis
• Bateson coined ‘genetics’ (1905) from pangene
• Wilhelm Johanson coined the term ‘gene’ (1909) from genetics.
 Alleles
• Mendel established the concept of different versions of the same gene, but did not use the term ‘allele’
• Allelomorph was coined by Muller much later; there are in fact a whole system of ‘morphs’ which describe various aspects
of function of the allele; amorph, hypomorph, hypermorph, antimorph and neomorph
• We tend to just use the shortened term ‘allele’ to describe different forms of the same gene.
• Important terms:
homozygote (aa or AA)
heterpzygote (Aa)
heterozygosity – the probability that two alleles selected at random from a population will be different
homozygosity – the probability that two alleles selected at random from a population will be the same
 Mendel recap

Heterozygote crosses give a classic 3:1 ratio of

phenotypes, and three genotypes.
 Hardy-Weinberg recap
• Alleles exist at frequencies within populations (suppose 0.85 [= 85%] of alleles were type
‘A’, and 0.15 were of type ‘a’, ie p =0.85 and q=0.15. These proportions always add up to 1
[(p + q)2 = 1 ].
• The Hardy-Weinberg equation allows one to calculate the expected proportion of
genotypes
p2 + 2pq + q2 = 1
0.73 AA, 0.25 (Aa), 0.02 (aa)
• The proportions of genotypes are designated P (for AA), R (for Aa) and Q (for aa). The
allele frequency p can be recalculated:
p’= P + ½ R
• Can be used to estimate number of carriers of genetic disorders, with quite surprising
results e.g. cystic fibrosis affects 1/1600 individuals
q2 = 1/1600
q = 0.025
Hardy-Weinberg tells us that 2pq = 2(1-q)q = 2 x (1 – 0.025) x 0.025 = 0.05
therefore 1/20 people are carriers (heterozygotes) despite the rarity of the condition.

• Can calculate the expected genotype proportions

• The resultant proportions show that p and q do not change from generation
to generation, answering Punnet’s question

• demonstrates that variation is preserved under particulate inheritance

• This system is used as a null basis in evolutionary studies – it shows what you
expect to see in genotype frequencies when evolution is NOT occurring.
Hardy-Weinberg Assumptions

Some important assumptions are required for Hardy-Weinberg Equilibrium

• Panmixis

• no selection

When populations are not in equilibrium, it is because these two assumptions

have been broken (e.g. inbreeding, nonrandom mating because of
subpopulations, action of selection)
 Over time gene frequencies change
• Taking the previous example where p = 0.85, and q = 0.15, imagine a
population of 1000 people.
• We expect there to be 730 AA (1000 x 0.73), 250 Aa and 20 aa genotypes
according to Hardy-Weinberg.
• In reality, when we move from one generation to the next, we are taking a
random sample – with a 0.85 probability of selecting a gamete of type A, we
would on average expect to obtain 730 AA types if we selected 1000 times.
• In reality we would get a number close to 730, but probably not exactly 730-
perhaps 713.
• If we got 713 AA individuals in the next generation, then p will have
wandered slightly in frequency to 0.84.
• This process of wandering allele frequencies was realized by Sewall Wright,
and is called Random Genetic Drift.
Random genetic drift

• The importance of random genetic drift has been much debated

over the last 80 years
• Drift is more pronounced in small populations so its effects are
more rapid
• Small populations are capable of carrying less diversity
• Random Genetic drift is the base upon which the rest of
evolutionary activity sits
• Ultimately, drift removes variation.
 Drift and Structure
• Populations differentiate over
time because of independent
processes of random genetic
drift
• We can consider the
heterozygosity (or
homozygosity) of such
populations.

differentiation
 Heterozygosity to measure populations

HT
Y HS
X HS

• We can express how much populations have differentiated using the concept of heterozygosity
• Heterozygosity is the probability of picking two alleles that are different
• We can calculate this probability ignoring the populations (ie total Ht), or calculate the
heterozygosity of each population separately.
• The heterozygosity of sub populations is always lower than the total heterozygosity

Total heterozygosity (Ht) Subpopulation heterozygosity (Hs)

8 red, 7 green Population X: 6 red, 1 green Population Y: 2 red, 5 green
P(same) = p(RR) + p(GG) = (8/15)2 + (7/15)2 = 0.502 P(same) = (6/7)2 + (1/7)2 = 0.755 P(same) = (2/8) 2 +(6/8) 2 = 0.625
P(different) = 1 – p(same) = 1 – 0.502 = 0.498 p(different) = 1-0.755 = 0.245 P(different) = 0.375
Ht = 0.498
Hs = (Hx + Hy)/2 = (2.45 + 0.375)/2 = 0.31
 Wright’s fixation indices (Fst) to measure
structure (population differentiation)

HT
Y HS
X HS

• Fst gives a measure of how differentiated populations are: range from 0-1.

FST = HT – HS • When a population is fractured into subpopulations, the heterozygosity

decreases (we lose variation)
HT • What happens to homozygosity?
• What happens to homozygosity when populations fuse?

FST = 0.498 – 0.31 = 0.38

0.498
There are lots of variations of FST, such
as RST and GST
Can we calculate the genotype frequencies in
a subdivided population?

HT
Y HS
X HS

Yes……if we know the Fst (proportion of reduction in heterozygosity):

AA = p2 + pqFst
Aa = 2pq – 2pqFst
aa = q2 + pqFst
 What’s structure again?
Populations with structure
HT
Y HS
X HS

Populations with no structure

HT
Y HS
X HS

Structure is differentiation of subpopulations – basically picking up non-random mating

 Differentiation and migration

habitat corridor
Gene flow counters the effects
of differentiation acting to
homogenize.

1
FST = So, for FST = 0.38 in example on
1 + 4Nm
previous slide,
Nm = [(1/FST-1)/4] = 0.41
Number of migrants
per generation So for N=100, m = 0.0041
 What separates populations?

• Could be space
• Could be time
• Could be another niche aspect
 Structure viewed through the program
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See supplementary course information for Pacific Islanders structure study

See Origins p96

inbreeding
P = 1/3 R = 1/3 Q = 1/3

p = 0.5
AA Aa aa
q = 0.5

p = 0.5
q = 0.5 P = 5/12 R = 1/6 Q = 5/12

• Inbreeding also reduces the heterozygosity, but leaves allele frequencies unaffected in a very similar
way to structure (both affect random mating)
• We can describe the extent of inbreeding with the inbreeding coefficient F
• H0 is the heterozygosity with no inbreeding, HI is the reduced heterozygosity caused by inbreeding
AA = p2 + pqF
F = H0 – HI = 1/3 – 1/6 = 1/2
Aa = 2pq – 2pqF
H0 1/3 aa = q2 + pqF

Don’t understand? see p135 Principles of population Genetics 3 rd Ed Hartl & Clark
 Inbreeding depression

Inbreeding depression in white clover (non-inbred on left, inbred on right)

 Outbreeding: heterosis

Figure 1.Phenotypic heterosis in the B73 ×

Mo17 hybrid. Representative B73, Mo17, and
F1 hybrid ears and plants are shown. Note the
increased size of the two hybrid ears and three
hybrid rows relative to the two inbred parents
(left, Mo17; right, B73).

See supplementary course information for heterosis review

 The effects of small populations: founder
effects

Ernst Mayr

• Founder effect: the founding of a new population by very few individuals

representing fraction of the genetic variation of the source population (a sampling
effect).
• Can lead to high frequencies of unexpected genotypes
• Proposed as a mechanism for speciation

The reduced variability of small populations is not always due to accidental gene loss, but sometimes to the fact
that the entire population was started by a single pair or by a single fertilized female. These “founders” of the
population carried with them only a very small proportion of the variability of the parent population. This
“founder” principle sometimes explains even the uniformity of rather large populations, particularly if they are
well isolated and near the borders of the range of the species (Mayr 1942, p. 237).
 Ellis-van Creveld syndrome and the Amish

• The Old Order of Amish

• Founded by a small
group and largely
inter-marrying
• Several genetic
diseases are unusually
common
• 6-fingered dwarfism (an
autosomal recessive).
All 82 studied cases are
descendants of Samuel
King and his wife.
Nature Genetics  24, 203 - 204 (2000)
OMIM #225500
 The effects of small populations:
bottlenecks
• Small populations can hold less diversity than large ones, because drift removes variation quickly from small
populations
• Bottlenecks cause ‘genetic erosion’

Population
size

Genetic
variation

time