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

Lecture Outline

1)  The Amish

Hybrid Zones

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

"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."

Alan R Shuldiner M.D.

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!

As names are unlikely to 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.

The Genetics of Amish Populations 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

Q1) Why would we expect to see greater genetic drift on the Y chromosome compared with other parts of the genome?

Questions

Q2) How can Rh –ve have reached high frequency when it is selected against?

A)  Smaller effective population size

(Q1.2 How much smaller?)

A)  Drift acts on all loci, Even those subject to selection

The Genetics of Amish Populations 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.

The Genetics of Amish Populations 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%.

The Genetics of Amish Populations 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

The Genetics of Amish Populations 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?

The Genetics of Amish Populations 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.

Lecture Outline

1)  The Amish

Hybrid Zones

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.

Inbreeding and Identity by Descent Global distribution of marriages between couples related as second cousins or closer

Inbreeding and Identity by Descent 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 self-fertilisation.

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.

Inbreeding and Identity by Descent 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.

Inbreeding and Identity by Descent 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.

Inbreeding and Identity by Descent 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

Inbreeding and Identity by Descent

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.

Questions?

Lecture Outline

1)  The Amish

Hybrid Zones

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.

Lecture Outline

1)  The Amish

Hybrid Zones

•  Fused:Fused

•  Unfused : Unfused

•  Hybrid

Meiotic combinations

Hybrid Zones

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

Hybrid Zones

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

Questions?

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!

Lecture Outline

1)  The Amish

Hybrid Zones

Inbreeding and Identity by Descent

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.

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.

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.

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

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 2p(1-p) (1-p)2

p2 2pq q2

gAA + gAa = 50/1000 = 0.05 gaa = (1 - 0.05) = 0.95

p2 = 0.95 p ≈ 0.974679

gAa = 2p(1-p) ≈ 0.04936 gAA = (1-p)2 ≈ 0.00064

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