Polymorphism: the raw material of evolution

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Polymorphism the raw material of evolution
E.g. Podarcis melisellensis is a medium-sized
Lacertid lizard, which inhabits the Eastern
Adriatic coastal region and many of the thousands
of islands in the Adriatic Sea. There is an
obvious polymorphism in the colouration of
abdomen and throat within this species adult
males are orange, yellow or white females are
yellow or white. These colours can be found in
different populations, but the frequency of the 3
morphs varies.
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Our example Cepaea nemoralis
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BACKGROUND Alterations of the HER2
proto-oncogene have been implicated in the
carcinogenesis and prognosis of breast cancer. A
polymorphism at codon 655 (GTC/valine to ATC
/isoleucine Val655Ile) in the transmembrane
domain-coding region of this gene has been
identified and may be associated with the risk of
breast cancer.
Journal of the National Cancer Institute, Vol.
92, No. 5, 412-417, March 1, 2000 Xie et al.
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Understanding the Mendelian view of polymorphism,
and the nature of fitness differences helps
overcome some difficulties with understanding the
genetics of evolution that troubled Darwin
himself. Michael Bulmer (2004), has set out the
main issues Fleeming Jenkin argued that
natural selection would be ineffective in
selecting a rare sport (mutant) because it
would be swamped by backcrossing to the normal
population. Bulmer (2004) BJHS 37(3) 281-297
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Jenkins argument as an illustration steeped in
the ingrained racism of the time he supposed
that a white man was wrecked on a desert island
inhabited by Africans Our shipwrecked hero
would probably become king he would kill a great
many blacks in the struggle for existence he
would have a great many wives and children, while
many of his subjects would live and die as
bachelors. In the first generation there will be
some dozens of intelligent young mulattoes, much
superior in average intelligence to the negroes.
We might expect the throne for some generations
to be occupied by a more or less yellow king but
can any one believe that the whole island will
gradually acquire a white, or even a yellow
population?
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Paul Janets version Paul Janet, the late
nineteenth-century French philosophical writer
and opponent of Darwinism, supposed that dark
skin colour was an advantage in hot countries,
and he imagined that in one of these countries
there was a white population among whom a single
black person appeared. He would marry a white
person, and their child would be mulatto, their
grandchild quadroon, and so on, until eventually
any hint of dark colour would disappear along
with any advantage.
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A traditional interpretation is that this was a
valid objection to Darwinism given the blending
theory of heredity current in the nineteenth
century, but that the problem vanished with the
acceptance of Mendelism. Why?
As we saw in our revision of the first year
material, the particulate inheritance means that
back-crosses will comprise of heterozygotes and
the original homozygotes (and occassionally some
of the sport homozygotes).
Actually as AS Davis, a maths teacher from Leeds
Grammar School, pointed out in 1871 that the
logic of the back-crossing argument is actually
wrong, even if blending inheritance was what
happened, since the reduced advantage for each
individual in successive generations would be
counter-balanced by the greater number of
individuals.
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The neo-Darwinian synthesis understands natural
selection as a process acting on the genetic
variation within a population. What explains
the existence of this polymorphism?
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Explaining polymorphism (the raw material for
evolution) and differentiation
Four fundamental processes Origin
Mutation Spread or loss within a
population Genetic drift and Selection Movement
from one population to another Gene flow
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At the most fundamental level, mutation. But why
are different alleles present in the population
at any one time? In other words why are
populations polymorphic? Drift tends to fix
alleles, but in large populations, or a network
of small populations connected by gene flow, this
may take so long that there is an appreciable
period when more than one allele survives.
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In the introductory lectures we considered one
form of selection that could maintain
polymorphism heterozygote advantage. It is
important to remember that there are other forms
of balancing selection. The example of human
left-handedness serves to remind us that it is
not enough to find that some selection processes
act to increase or decrease and others to
decrease it. There must be frequency dependence.

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The devil is traditionally left handed (sinister)
Justice is right-handed!
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Leaving aside superstition, perhaps based on the
time-honoured principle of picking on minorities,
left-handedness seems to be associated with
several fitness costs, such as a lower height
or a reduced longevity (e.g. Aggleton,
Kentridge and Neave, 1993 Coren and
Halpern,1991 Gangestad and Yeo, 1997 McManus
and Bryden, 1991 many more on the
web-site). The costs reported in the literature
are not likely to be frequency-dependent. A
frequency-dependent advantage is therefore
required to explain the maintenance of the
polymorphism (see Raymond references on web
site).
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How do we know its frequency relatively unchanged?
Why does it need a frequency dependent advantage
to explain its persistence at a similar
frequency?
What might this advantage be?
How could we evaluate this hypothesis
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Examples of genetic markers used in population
surveys. Visible phenotype Protein
electrophoresis RFLP analysis Fingerprinting
(minisatellite, microsatellite) DNA sequencing
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Examples of genetic markers used in population
surveys. Visible phenotype Protein
electrophoresis RFLP analysis Fingerprinting
(minisatellite, microsatellite) DNA sequencing
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http//www.cf.adfg.state.ak.us/geninfo/research/ge
netics/techfac/images/allozyme/gelload4.jpg
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Not all alleles are distinguished (30), even so
there is a huge amount of polymorphism so much
so that it lead to a radical change in
evolutionary theory.
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Differences between human individuals were
estimated to be 1 per 1000 bp. This has
subsequently been verified by DNA sequencing
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The estimates of differences between species have
been verified by comparisons of DNA sequence and
protein sequence. They indicate roughly 1 aa
substitution every 10 years, And many more DNA
substitutions.
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Examples of genetic markers used in population
surveys. Visible phenotype Protein
electrophoresis RFLP analysis Fingerprinting
(minisatellite, microsatellite) DNA sequencing
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Short tandem repeats (STRs) 2-6 bp repeat
units. High mutation rate (up to 10-2
?) Amplified by PCR Automated screening using
fluorescent primers and laser detection Used in
forensic science
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E.g. Mauritius Kestrel
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Examples of genetic markers used in population
surveys. Visible phenotype Protein
electrophoresis RFLP analysis Fingerprinting
(minisatellite, microsatellite) DNA sequencing
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Types of comparison Frequency differences
between populations Trees Populations which
differ little in their allele frequencies are
assumed to have a recent common
ancestor Problems estimates are disrupted by
gene flow, drift, selection
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Number of differences in a DNA sequence (nb. In
this case it is individual alleles that are being
compared not whole populations) Trees the
smaller the number of differences the more recent
the common ancestor is assumed to be. But
estimates are disrupted by recombination (use
mitochondria, chloroplasts, Y-chromosome) by
recurrent mutation, and by selection.
In this case A, B C could be sequences from
different species or within a single population!
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Hardy-Weinberg principle The allele frequencies
are related to genotype frequencies (given
certain assumptions) AA p2 AB
2pq BB q2
Sperm
p
p2
pq
Eggs
pq
q2
q
q
p
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Non overlapping generations in a diploid sexual
organism Random mating in a large
population Negligible mutation, migration
selection
Note difference from Punnet square.
How many generations to equilibrium?
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Detecting deviations from HW expectations eg
Results from final year project on Culex
molestus
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Allozyme genotype AA AB BB Observed
Counts 30 10 10 Expected counts 24.5 21 4.5 O-
E 5.5 -11 5.5 (O-E)2/E 1.23 5.76 6.72 ?21
3.71 one d.o.f. nb do not do on table of !
Calculation of expected for AA P(30x2 10) / 100
0.7 P2 x 50 24.5
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Was something wrong with scoring? Is this the
Wahlund effect? Undectected population
sub-division Population 1 Population 2 High A
frequency High B frequency Predominantly
AA Predominantly BB
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HW calculations can also be used to assess allele
frequencies from genotype frequencies eg. Colour
morphs eg. Blood groups Where homozygotes
cannot be distinguished from heterozygotes. Expec
ted number of the dominant phenotype is P2
2pq
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HW calculations can also be used to assess the
effects of Population bottlenecks founder
events Eg if a population is reduced to 4
individuals then the probability of them having
all the same allele is Prob(all homozygous
for allele 1) Prob(all homozygous for allele
2) Prob(all homozygous for allele 3) etc.
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Ie P18P28P38... eg. 0.43 for bi-allelic
locus, p10.9,p20.1 0.008 for bi-allelic
locus, p10.5,p20.5 Lesson bottlenecks have
to be sustained to result in substantial loss of
genetic variation.