Lectures for Week 8�Selection, Gene Flow, and�

Mutation

Andrea Hatlen

Announcements •  The workshop is this week. The assessment completed

during the workshop will count for 20% of your score in this course.

•  Please go through the PopG tutorial, you will be tested upon entering the workshop.

•  Please bring a pencil (and eraser)

•  Make sure you know your Student ID number

•  Don’t forget: –  Tuesday 12 Nov. 14:00-17:00, FB 1.15a à C800, F850, Z100 –  Thursday 14 Nov. 15:00-18:00, FB 115a à C300, C400, C431

–  Friday 15 Nov. 14:00-17:00, FB 1.23 à C100

Lecture Outline

1)  Types of Selection

2)  Gene Flow

3)  Mutation

4)  Mini Review Session

The Drift Practical

Mutation Gene Flow Selection

Summary of Week 6 Lectures

1)  Defined our terms –  Gene, Locus, Allele, Genotype, Phenotype, Gamete, Zygote,

Dominant, Recessive

2)  Introduced genetic drift –  Stochastic change in allele frequencies –  Can lead to fixation or loss of alleles.

–  Stronger in small populations, eg. in founder events.

3)  Touched on Selection –  Selection occurs against a background of drift

–  Related to ‘fitness’ of a particular genotype

Any Questions?

Darwin on Selection In 1859 Darwin rocked the foundations of modern science with the publication of his seminal work “On the Origin of Species by Means of Natural Selection”

“When on board H.M.S. “Beagle”, as a naturalist, I was much struck

with certain facts in the distribution of the inhabitants of South America, and in the geological relations of the present

to the past inhabitants of that continent. These facts seemed to me to

throw some light on the origin of species – that mystery of mysteries, as

it has been called by one of our greatest philosophers.”

Sold for £103,250 in 2009

Darwin on Selection Darwin looked at selection, both artificially and in the wild, and concluded that it could lead to systematic changes over long timescales.

“I can see no good reason to doubt that female birds, be selecting, during thousands of

generations, the most melodious or beautiful males, according to their standard of beauty,

might produce a marked effect.”

“That most skillful breeder, Sir John Sebright, used to say, with respect to pigeons, that ‘he

would produce any given feather in three years, but it would take him six years to obtain a

head and beak’”

Darwin on Selection

Darwin was unaware of Gregor Mendel’s work on heredity, and as

such many of the details of Darwin’s theory were wrong (see “Pangenesis”).

However, the central principles of evolution by natural selection hold

true to this day.

We can use our rigorous notation from earlier lectures to obtain a more up-to-date perspective on selection.

Darwin on Selection

Selection occurs at the level of the…

Gene Allele

Phenotype

Population

Locus Nucleotide

But genes can relate to phenotypes in various different ways…

Types of Selection If an allele is dominant then the heterozygote has the same phenotype as the homozygote.

If an allele is recessive then the heterozygote has the same phenotype as the other homozygote.

A is dominant

A is recessive

If A is dominant then the heterozygote has the same fitness as the homozygote

If A is recessive then the heterozygote has the same fitness as the other homozygote

Types of Selection

wAA = 1 wAB = 1 wBB = 0.8

wAA = 1 wAB = 0.8 wBB = 0.8

Types of Selection Recall the picture of drift + selection from earlier lectures…

Don’t be seduced by the smoothness of these lines – drift is still occurring in the background!

Types of Selection

Q. How can we explain the shape of this curve?

Types of Selection

When A is at high frequency B is rare, and therefore B is most often present in heterozygotes. From a fitness point of view there is nothing to differentiate AA from AB individuals, and so there is very little phenotypic variation for selection to operate on.

This is the same reason it is difficult to eliminate deleterious recessive

alleles from a population, for example in Ellis-van Creveld syndrome.

Types of Selection

Q. How can we explain the shape of this curve?

Types of Selection

Even when the A allele is at high frequency the B allele is always ‘visible’ From a fitness point of view selection is always acting to drive out B alleles

Dominant disorders can be driven out of a population more easily than

recessive disorders, and hence there are less of them around.

Marfan syndrome

Other types of selection include heterozygote advantage (overdominance)…

and heterozygote disadvantage (underdominance)…

Types of Selection

wAA = 0.8 wAB = 1 wBB = 0.8

wAA = 1 wAB = 0.8 wBB =1

Types of Selection

Q. How can we explain the shape of this curve?

Types of Selection

There is a balance between having enough A alleles and having too many!

A alleles rare: mostly present in

heterozygotes

Selection for A

A alleles common: mostly present in

homozygotes

Selection against A

The equilibrium frequency is the point at which these forces balance out

Types of Selection

A classic example of heterozygote advantage is sickle-cell anemia.

Types of Selection

A classic example of heterozygote advantage is sickle-cell anemia. –  The sickle-cell allele (HbS) is autosomal recessive; meaning only

homozygotes are affected –  However, HbS also confers partial resistance to malaria, meaning in

certain parts of the world the heterozygote has the highest fitness

Historical distribution of malaria and HbS allele

Types of Selection

Types of Selection

Q. How can we explain the shape of this curve?

Types of Selection

One cause of heterozygote disadvantage is the formation of hybrids, but more on this later…

Questions?

Announcements •  The workshop is this week. The assessment completed

during the workshop will count for 20% of your score in this course.

•  Please go through the PopG tutorial, you will be tested upon entering the workshop.

•  Please bring a pencil (and eraser)

•  Make sure you know your Student ID number

•  Don’t forget: –  Tuesday 12 Nov. 14:00-17:00, FB 1.15a à C800, F850, Z100 –  Thursday 14 Nov. 15:00-18:00, FB 115a à C300, C400, C431

–  Friday 15 Nov. 14:00-17:00, FB 1.23 à C100

Lecture Outline

1)  Types of Selection

2)  Gene Flow

3)  Mutation

4)  Mini Review Session

Gene Flow

So far we have only looked at the effects of drift and selection within a single panmictic population. To understand how evolution works across different populations we must talk in terms of “gene flow”.

•  Gene flow can be one-directional or multi-directional

•  Movement of individuals does not necessarily imply movement of genes!

Gene flow describes the processes by which individuals genes (or alleles) move from one population to another.

Gene Flow

In the absence of gene flow populations tend to become genetically differentiated from one another.

Gene Flow

In the absence of gene flow populations tend to become genetically differentiated from one another.

Gene Flow

In the absence of gene flow populations tend to become genetically differentiated from one another.

This is mainly visible in neutral loci, which are evolving under drift alone.

Gene Flow

Gene flow homogenises populations, and can recover lost genetic variation

Gene Flow Many populations are isolated, experiencing limited or zero gene flow. In this case we expect drift to lead to differentiation between populations.

Smaller numbers of differences are expected between close branches, larger differences between more distant branches

Gene Flow •  Branching patterns can also be

constrained by geographic boundaries within species. In this case, as before, drift leads to differentiation between distinct populations.

•  Patterns reflect the consequences of the spread of populations since the last ice age (ending 10,000 years ago), at the height of which most of Europe was inhospitable for the species that currently inhabit it.

•  Populations were restricted to refugia, and they become a relic population of a once more widespread species

Lecture Outline

1)  Types of Selection

2)  Gene Flow

3)  Mutation

4)  Mini Review Session

Mutation

Consider the following questions…

1)  What is mutation?

2)  What are some ways of classifying mutation?

3)  How does mutation interact with drift and selection?

Mutation

Mutation

•  The processes producing genetic variation

•  The original source of all genetic variation

•  A permanent structural alteration in DNA

In most cases, DNA changes either have no effect or cause harm, but occasionally a mutation can improve an organism's chance of surviving and passing the beneficial change on to its descendants.

Mutation Point Mutation One base exchanged for another

Insertion Extra base pair(s) inserted Deletion Base pair(s) lost Frameshift

Applies to insertions and deletions. Anything which changes the amino acid sequence being coded for

Mutation

There are also some larger mutational events that can occur, including…

•  Large-scale deletion/insertion events

•  Duplication

•  Inversion

•  Translocation

and some very large…

•  Polysomy

•  Whole genome duplication

Mutation

Without some process generating variation, eventually all alleles will become either fixed or lost over enough time

Mutation

Mutation can re-introduce lost genetic variation into a population

Mutation

•  Each gene copy experiences mutation at a rate μ

•  In a population of 2N genes this is a total mutation rate of 2Nμ

•  The chance of any one new allele going to fixation is 1/(2N)

•  Therefore…the probability of a new mutant allele going to fixation under drift alone is 1/(2N) * 2Nμ = μ

The rate of substitution is independent

of the population size

Questions?

Sneak Peek: The Workshop •  What happens when you make a population bigger? smaller?

(with drift or drift and selection) •  What about if you change the fitness of one genotype or

another (aka change selection pressures)? •  What about if there is mutation? or migration?�

Mini Revision Session Short questions…

1.  Define the terms Dominant and Recessive.

2.  How are relative and absolute fitness calculated?

3.  Is genetic drift stronger or weaker in a small population? Why?

Longer questions…

1.  Explain how random sampling from a finite population leads to stochastic changes in allele frequencies.

2.  Why do we expect many more carriers of recessive deleterious alleles than affected individuals?

3.  For an allele that is at a high frequency in a population, would selection be able to bring it to fixation faster if it is dominant or recessive? Why?

Mini Revision Session

I will not be providing model answers for all of the mini-revision session questions, as it is far more important that you think about these

questions yourselves! All of the answers are contained within the lecture notes of the past two weeks – once you familiarise yourself with this

material these questions should seem fairly straightforward.

Now is a good opportunity to ask me any questions

you have before the workshop