Evolution lectures WK9

Lectures for Week 9
Founder Effects, Inbreeding
and Hybrid Zones
Andrea Hatlen

Lecture Outline
1)  The Amish
2)  Inbreeding and Identity by Descent
3)  Allele Frequency Clines and the Formation of
Hybrid Zones
4)  Mini Revision Session

The Amish

•  The Amish are an Anabaptist Christian denomination in the
United States and Ontario, Canada
•  Known for their plain dress and limited use of modern devices
such as automobiles and electricity
•  Most speak a German dialect known as Pennsylvania Dutch

The Amish
There are approximately 12,000 Amish in Lancaster county. They are
descended from about 400 founders originating from the Swiss German
border with very little recruitment from other populations. The few
converts are well documented.

The Amish
Over the generations the number of descendants of these few founders
has grown and the population has therefore expanded (although more
people leave the community than join).

•  excellent records

•  large family size
•  restricted population
highly valuable for
genetic studies

1,225,366 names!

386,130 families!

The Genetics of Amish Populations
Alan
R
Shuldiner
M.D.

"Only about 200 Amish founders came from
Europe to the United States in the early
1700s," Shuldiner notes. "The Amish
population has grown to 30,000 in the
localized area of Lancaster County. While
diabetes does not occur more frequently in
the Amish than in other population groups,
the Amish are a closed population with a
ﬁxed gene pool, have very large families, and
essentially complete genealogies dating back
14 generations. It's quite a unique situation to
be able to study a speciﬁc group of people
who have particularly good characteristics for
genetic research."

The allele frequencies in the Amish population are atypical of the
communities from which they are descended in Europe because of…
1. 

Founder events: the ﬁrst
400 (or so) founders will
have, by chance, had an
atypical collection of genes

2. 

Further drift: the small
population size subsequent
to foundation will have lead
to further genetic drift.

Six of the founders names are responsible for 3/4 of those seen today and a full
1/4 are called Stoltzfus!

names are unlikely to
As
confer a selective advantage,
this change in the frequency
of names is most easily
explained as a random or
stochastic change. (Be
careful: they might be
associated with genes that
confer a selective advantage).
The same change would be predicted for Y chromosomes which are also
transmitted down the paternal line, and a similar change for mitochondrial DNA
which is passed down the maternal line.

•  Wilma Bias (John Hopkins University) looked at 30-35 genetic systems
giving evidence about 100-150 loci from one blood sample. The loci
range from the well known blood groups to soluble enzymes.
•  It is important to remember that, by
chance some loci will have larger changes
in allele frequency, some smaller –
although those on the Y chromosome
and mitochondria would be expected to
show greater changes.
•  Like the names, some loci show dramatic
frequency changes since foundation
15%-25% in the case of Rh- blood.

It is particularly important for expectant mothers to know their blood's Rh factor.
Occasionally, a baby will inherit an Rh positive blood type from its father while the
mother has a Rh negative blood type.

The baby's life could be in danger if the Rh negative mother's immune system attacks
the baby's Rh positive blood. To prevent this, the mother is injected with anti-RhD
IgG immunoglobulin so that the Rh positive erythrocytes from the baby’s blood in
her system are destroyed before her immune system ﬁnds them.

Rh –ve is almost
certainly selected
against

Questions

Q1) Why would we expect to see greater
genetic drift on the Y chromosome compared
with other parts of the genome?
A)  Smaller effective
population size
(Q1.2 How much smaller?)

Q2) How can Rh –ve have reached high
frequency when it is selected against?
A)  Drift acts on all loci,

Even those subject to selection

Ellis-van Creveld syndrome (know colloquially as “Six ﬁngered dwarﬁsm”) is
a recessive trait: genealogical studies show that it is only expressed when an
individual carries two copies of the allele.

Extremely rare in the population at
large, however…

…estimates are that 1/7 of the
present day Amish population carry
the gene
Perhaps only 1 of the 400 founders carried the allele in the ancestral
population (in a single copy, hence the allele frequency would have been
1/800). The allele may have subsequently drifted to high frequency.

This syndrome was described by Ellis and van Creveld in 1940. Very few
cases have been reported in the literature.
A follow up study was carried out by
McKusic et al. in 1964, which focussed on
the Amish population. Almost as many
affected individuals were found in this one
kindred as had been reported in all the
medical literature up to that time

McKusic et al. estimated that around 5 in
1000 Amish births resulted in EvC. From
this they estimated the frequency of
heterozygous carriers at around 13%.

How did they arrive at these numbers?

First, lets remember Hardy-Weinberg

Under random mating we expect to see Hardy-Weinberg
genotype frequencies:

p = allele frequency of one allele, q = allele frequency of the other

p2

2pq

q2

p2

2p(1-p)

(1-p)2

How did they arrive at these numbers?

Let us call the EvC allele the ‘A’ allele and any non-EvC allele
the ‘B’ allele. We will use the symbol gAA to refer to the
homozygous (affected) genotype frequency. This genotype
frequency was estimated at gAA=0.005 from observed
individuals and historical records

Under Hardy Weinberg proportions we would expect to see p2
homozygotes of this sort, where p is the allele frequency of
the EvC allele. Thus, p2=0.005 and from this we can estimate
that p≈0.07

Again, assuming Hardy Weinberg proportions we would expect
the genotype frequency of heterozygotes to be gAB=2p(1-p),
which works out at around gAB≈0.13

Notice that the proportion of carriers (gAB≈0.13) is much
larger than the proportion of affected individuals
(gAA=0.005 ).

Why might we generally expect to see this pattern in
recessive diseases?

Brief summary…

•  The Amish are a text-book example of genetic drift.
•  A number of disadvantageous alleles have drifted to high frequency, in
spite of the action of selection against them. This reminds us that genetic
drift affects all loci, not just those that are evolving neutrally.
•  Detailed records combined with a polite culture open to conversation
with scientists means that we can investigate genotype and allele
frequencies for certain conditions that would otherwise be hidden from
view.

Inbreeding and Identity by Descent
Genetic drift causes allele frequencies to change over time as a result of
sampling from a ﬁnite population. However, genotype frequencies are
expected to remain in Hardy Weinberg proportions every generation.

What can cause a deviation from these proportions is inbreeding: deﬁned as
non-random mating of relatives leading to the increased probability of
identity by descent.

The Amish actually avoid cousin matings (and closer), so the population is
actually less inbred that you would expect from a random mating
population.

Global distribution of marriages between couples related as second
cousins or closer

The probability of identity by descent due to relatedness between parents
can be measured by the parameter f.

In simple terms, f is the chance that the two gene copies in a diploid
individual are descended from the same copy in an earlier generation.

The greatest possible amount of
inbreeding occurs in selffertilisation.

In this case the two gene copies in
the offspring have a probability
f=1/2 of originating from the same
copy in the parent.

Consider an inﬁnitely large population of selﬁng diploids. Assume that every
individual in the starting population is a heterozygote.

Genotype frequencies change over generations until eventually we would be
left with only homozygotes. Notice that the allele frequencies have not
changed from the initial frequency of p=1/2.

In more complex forms of inbreeding the coefﬁcient f can still be worked out
by looking at pedigrees.

In this example the probability of identity by descent comes out at f=1/8.

Word of caution: The word inbreeding is a bit “fuzzy”
Some people include genetic drift as a sort of inbreeding, others do not.
Better to contrast genetic drift against consanguinity.

Drift and consanguinity are similar in some ways, and complete opposites in
others!
•  Both occur due to a build up of shared ancestry within a population.
•  Drift occurs as a result of ﬁnite population size, whereas consanguinity
could technically occur even in an inﬁnitely large population.
•  Drift results in a change in allele frequencies, but genotype frequencies
remain in HWE. Consanguinity results in a change in genotype
frequencies, but does not alter allele frequencies.

These two processes have different implications
for eg. disease


Bottleneck
Those deleterious recessive alleles that
drift up produce increased incidence of
the disorder. This is then reduced by
selection over subsequent generations.

Consanguinity
The incidence of each disorder is
increased, but selection reduces the
incidence rapidly.

Allele Frequency Clines
•  Biston betularia (the Peppered
Moth) exists in melanic and
wild-type phenotypes

•  As the melanic (A) allele is
dominant: both AA and AB
individuals express the black
colouration – hence wAA = wAB
•  Industrial melanism
hypothesis: selection in favour
of the melanic form post
industrial revolution

Selection in favour of a dominant allele…

Some evidence to support this: Mark recapture experiments found
that the ﬁtness of the melanic morph is higher in areas where they
are prevalent.

•  The industrial revolution did not lead to
the blackening of all trees. The Delamere
Forest near Manchester and Liverpool is
relatively unaffected but the peppered
moths are predominantly melanic there.
•  On the other hand the Gonodontis bidentata
(Scalloped Hazel), which are also melanic
right in the heart of the major industrial
centres, are predominantly non-melanic in
Delamere forest.
•  The difference between the two species
may be explained by their dispersal rates.
HOW?

Meiotic combinations
•  Fused:Fused

•  Unfused : Unfused

•  Hybrid

?

Hybrid Zones

The existence of this frequency cline can be explained by the reduced ﬁtness of
heterozygotes.
HOW?

Hybrid Zones

Gene ﬂow never gets far into the other population due to the
reduced ﬁtness of heterozygotes

A Complete(ish) Picture
We can start to build up a picture of what
evolution really looks like…
•  First and foremost there is genetic drift
•  There may also be some selection
acting
•  Gene ﬂow homogenises allele
frequencies between populations
•  Mutation introduces new
genetic variation into
populations that may have lost it
due to drift or selection
•  There are still many processes
missing from this picture!

Mini Revision Session

What is

the probability of identity by descent (f) of
an offspring of full sib parents (parents are brother
and sister with the same mother and father)?

First things ﬁrst; we need to draw a pedigree
of the offspring of full sib parents.
One thing that was confusing people is that
the question did not specify the genotypes of
either the parents or the offspring.
Remember that we are trying to work out the
probability of identity by descent – in
other words, the probability that the two
genes in the offspring are descended from the
same gene copy in an earlier generation. We
do not need to know any genotypes to work
this out! To make this point clear, I have
drawn genes in the grandparents as dots,
rather than letters.

1.  We know that one gene copy in the
offspring came from the father, and one
from the mother. The question is; where
did each of these come from in the
grandparental generation?

2.  Looking just at the paternal side, there is
an equal chance that this gene came from
any of the 4 gene copies in the
grandparents. Thus, we can say that the
probability of each of these events is ¼.

2.  Looking just at the paternal side, there is
an equal chance that this gene came from
any of the 4 gene copies in the
grandparents. Thus, we can say that the
probability of each of these events is ¼.
3.  The same is true of the maternal side. The
probability of this gene descending from
each of the genes in the grandparents is
¼.

4.  Combining this knowledge, we can work
out the probability that both offspring
genes are descended from the same copy.
Looking at the ﬁrst grandparental gene (ie.
the ﬁrst black dot), we know that the
probability of both the maternal and
paternal genes coming from here is
¼ × ¼ = 1/16.

4.  Combining this knowledge, we can work
out the probability that both offspring
genes are descended from the same copy.
Looking at the ﬁrst grandparental gene (ie.
the ﬁrst black dot), we know that the
probability of both the maternal and
paternal genes coming from here is
¼ × ¼ = 1/16.
5.  The same is true of the second
grandparental gene (second black dot). In
fact, this is true of any of the 4
grandparental genes.

6.  In summary; there are 4 ways that the
offspring genes could be descended from
the same gene copy. Each of these has
probability 1/16. Thus, the overall
probability of identity by descent is…
1/16 + 1/16 + 1/16 + 1/16 = 4/16

Or

f = 1/4


In

a random mating population, there is a disease
that is encoded by a dominant allele. About 50 out
of 1000 individuals have this disease. Calculate the
genotype frequencies for AA, Aa, and aa.

p2

2pq

q2

p2

2p(1-p)

(1-p)2

+

gAA + gAa = 50/1000 = 0.05

gaa = (1 - 0.05) = 0.95
p2 = 0.95
p ≈ 0.974679

gAa = 2p(1-p) ≈ 0.04936

0.05
gAA = (1-p)2 ≈ 0.00064

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