Transcript Lectures 7 & 8 The Genetic Basis of Evolution

Selection, Gene Flow,
and Mutation
Dr David Hone
Rm 6.14 Fogg
Office Hrs: Tuesday 2-4 pm
Announcements
•
The workshop is in week 8. 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
•
Class split TBC
Lecture Outline
1) Types of Selection
2) Gene Flow
3) Mutation
4) Mini Review Session
The Drift Practical
Selection
Mutation
Gene Flow
Summary of Week 5 Lectures
1) Defined 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, e.g. 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.
“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’”
“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.”
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
(e.g. blending). 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
Locus
Allele Population
Phenotype
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.
A is dominant
If an allele is recessive then the heterozygote has the same
phenotype as the other homozygote.
A is recessive
Types of Selection
If A is dominant then the heterozygote has the same fitness as the
homozygote
wAA = 1
wAB = 1
wBB = 0.8
If A is recessive then the heterozygote has the same fitness as the
other homozygote
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
Types of Selection
Other types of selection include heterozygote advantage
(overdominance)…
wAA = 0.8
wAB = 1
wBB = 0.8
and heterozygote disadvantage (underdominance)…
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
A alleles common:
mostly present in
homozygotes
Selection for A
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
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 describes the processes by which individuals genes (or
alleles) move from one population to another.
• Gene flow can be onedirectional or multi-directional
• Movement of individuals does
not necessarily imply
movement of genes!
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.