QMUL SBCS 174 - Genetic basis of evolution.

1. The Genetic Basis of Evolution

2. • Additional reading for these
lectures: ‘Evolution’ by Barton et
al, Part III. Available in the
library

3. Lecture Outline
1) General Introduction
2) Defining our Terms
3) Genetic Drift
4) Selection

4. Away from pan-selectionism
• Most people don’t really
understand evolution
• A very common mistake is
to take a pan-selectionist
view. “Everything can be
explained by selection.”
• This is an oversimplified
‘storybook’ view of evolution

5. Away from pan-selectionism
Pan-selectionist would
try to come up with a
story for why the trunk
confers a selective
advantage
!
This is not much better
than a ‘just so’ story
“Then the elephant sat back on his little haunches, and pulled,
and pulled, and pulled, and his nose began to stretch”

6. Away from pan-selectionism
My job is to de-program you from the pan-selectionist heresy

7. Away from pan-selectionism
• First and foremost is genetic drift which goes on in all
populations and accounts for much of the genetic
differentiation between individuals, between populations of the
same species and between different species.
• Second we must understand the action of the basic modes of
selection. It’s not a case of choosing between selection or
drift; selection occurs against a background of drift.
DRSELECITFION T

8. Lecture Outline
1) General Introduction
2) Defining our Terms
3) Genetic Drift
4) Selection

9. Defining our Terms, Part I
We need to understand the following vocabulary, so that we
can use the words accurately and confidently:
1. Gene
2. Locus
3. Allele
4. Genotype
5. Phenotype
Write down your best definition of
each of these terms

10. Definition: Gene
Gene
• Segregating and heritable determinant of the phenotype.
• The fundamental physical and functional unit of heredity, which
carries information from one generation to the next.
• A segment of DNA, composed of a transcribed region and
regulatory sequences that make possible transcription.
• Human Genome Nomenclature Organization: “a DNA
segment that contributes to phenotype/function”
• Long distance regulation? Alternative splicing?
Our definition of the gene is getting
fuzzier all the time

11. Definition: Locus
Locus (pl. loci)
• The position on a chromosome of a gene or other chromosome
marker
• Can also refer to the DNA at that position
• The use of locus is sometimes restricted to mean regions of DNA
that are expressed
[Source: DOE Primer on Molecular Genetics]

12. Definition: Locus
We can find specific DNA sequences in the genome by going
FISHing. (FISH = flourescence in situ hybridisation)
N-myc locus on 2p24 (normally)

13. Definition: Locus
Multiple copies of n-myc rearranged in a homogeneously
staining region (HSR) on a different chromosome - one of the
classic ways in which n-myc amplicons are formed.

14. Definition: Allele Allele
• Variant of a gene. Different alleles can lead to different
phenotypes
•Diploids have two copies of each gene.
A homozygote possesses two copies of the same allele, while a
heterozygote possesses two different alleles
Allele Frequency (proportion)
Frequency of A allele:
p = 11/16 = 0.6875
(i.e. 2×Homozygotes + Heterozygotes)

15. Definition: Genotype Genotype
•The genetic makeup of an individual
• A description of the alleles possessed by an individual
Genotype frequency
0.5 0.375 0.125
Under random mating we expect to see
Hardy-Weinberg genotype frequencies:
p2 2p(1-p) (1-p)2

16. Definition: Genotype
When alleles are rare they are more commonly found in
heterozygote genotypes
Remember this graph – it will come in very handy when
we come to think about drift and selection later on!

17. Definition: Phenotype
Phenotype
• The physical characteristics of an individual
• Composed of ‘traits’
• Interaction of genes and environment. Genetic component of the
phenotype is heritable, environmentally acquired component of
phenotype is not.
•What about the ‘extended’
phenotype?
• Does this cased Caddisfly’s
shell constitute a phenotype?

18. Defining our Terms, Part II
We need to understand the following vocabulary, so that we
can use the words accurately and confidently:
6. Gamete
7. Zygote
8. Dominant
9. Recessive
Write down your best definition of
each of these terms

19. Definition: Gamete & Zygote
Gamete
• Germline cell that is able to unite with another of the opposite sex
during sexual reproduction
• Produced by meiosis
• Contains half the chromosomes of the parents
Zygote
• The earliest developmental stage
of the embryo
• Produced by the fusion of
two gametes

20. Definition: Dominant & Recessive
Which of these statements are True and which are False…
• The terms ‘dominant’ and ‘recessive’ apply to genes
• The terms ‘dominant’ and ‘recessive’ apply to alleles
• The dominant allele is the one that is selected for
• If the alleles are A and a then A is the dominant allele
• The dominant allele is the most common in the
population
• The dominant allele expresses its phenotype even when
present in a heterozygote
• If A is dominant over a then individuals who are AA and
Aa have the same phenotype (but…)
(Convention,
not a rule)

21. Bringing it all together
• Two alleles of the same gene, called
A and a.
• A homozygous AA individual mates
with a heterozygote. We can list the
gametes that can be produced by
each parent.
• These gametes fuse to form zygotes,
and hence offspring individuals of
the next generation.

22. Bringing it all together
•What genotype proportions would we
expect to see in the zygotes?
•We know that A is dominant over a, and
codes for red feathers. What proportion
of individuals in the offspring generation
would we expect to have red feathers?
• There are two processes that could
cause an offspring not to have red
feathers – one that I’ve mentioned and
what that I haven’t yet. What are they?
Environment
Mutation

23. Questions?

24. Lecture Outline
1) General Introduction
2) Defining our Terms
3) Genetic Drift
4) Selection DRIFT

25. Genetic Drift
• Genetic drift describes the process by which allele frequencies
change over time due to the effects of random sampling.
• Drift takes place as a consequence of finite population size.
• It is not a case of choosing between selection or drift. Genetic
drift takes place in all populations, and any selection must
occur against this background of drift.
• Genetic drift can help us to understand differences between
individuals, between populations of the same species and
between different species.

26. Genetic Drift
How does it work?...
• Imagine a finite population of individuals.
Let us assume that every individual in the
population is as fit as every other.
Assume complete random mating.
• Take a particular individual of the
offspring generation. It is equally likely
that any member of the previous
generation is the parent.
•We can go even further – any gene copy
in the offspring generation has an equal
chance of coming from any gene copy in
the parental generation.

27. Genetic Drift
We can simplify the process…
• Just focus on the gametes of each
generation.
•We can say that the next generation of
gametes is produced by sampling with
replacement from the previous generation.
• By pure chance we might sample a
particular allele more or less often than
expected, causing the allele frequencies to
change from one generation to the next.
• This occurs generation after generation,
causing allele frequencies to drift over time.

28. Genetic Drift: Example
Two alleles called A and a. Starting allele frequency of A is p=0.6,
meaning the starting allele frequency of a must be (1-p)=0.4
Generate next generation by sampling with replacement from
previous generation
!
Same process again. Notice that the allele frequency drifted from
one generation to the next.

30. Genetic Drift
Graph of a particular allele frequency as it changes over time
Simulation starting with 100
heterozygous individuals
(p=0.5)
(population size
= 100 diploids)
Notice that eventually the allele frequency gets stuck at p=1.
• It gets stuck here because there is only one allele left to sample!
• This is called fixation. The allele has become fixed in the population.
• The other possibility is that the allele gets lost, in which case the other
allele must have become fixed (assuming two alleles)

31. Genetic Drift
Look at many replicates of the process of evolution
• Equal chance of drifting up or down
• If we leave enough time we can be certain that one or other
allele will become fixed, and the other will become lost.
• Which of these events is more likely depends only on the
starting allele frequency. There is no selection in this model!

32. Think about it….
!
Would genetic drift be stronger in a
smaller population or a larger
population?

33. Genetic Drift
Genetic drift is stronger in a small population than in a large
population
The effect of random sampling is greater in a small
population than in a large population
!

34. Genetic Drift
One place that drift can be particularly strong is when a
population undergoes a bottleneck
The human population has almost certainly gone through
several such bottlenecks on way out of Africa

35. Genetic Drift
At the moment our model of how a population evolves is an
extremely simplified cartoon of real life. We could make it more
realistic by…
• Allowing for two separate sexes
• Allowing the population size to change over time
• Using a more realistic model for how many offspring
an individual might have
• Etc.
These modifications make very little difference to the process of
drift! The key fact is always true:

36. Lecture Outline
1) General Introduction
2) Defining our Terms
3) Genetic Drift
4) Selection DRSELECITFION T

37. Defining Fitness
We know that selection occurs because different individuals
have different fitness, but what exactly do we mean by this
word fitness?
Write down an evolutionary definition of the word fitness.
Consider the following questions…
1) What is fitness?
2) Is fitness a property of alleles, genes,
genotypes or phenotypes?
!

38. Defining Fitness
The word fitness in an evolutionary context can be defined
as…
“The expectation of the number of descendant lineages at the
same stage of the life cycle in the next generation.”
Low
fitness?
High
fitness?
I will use ‘fitness’ to mean a property of genotypes - not alleles
or even phenotypes.

39. Calculating/Estimating Fitness
Example: a population of 4 individuals mate and produce offspring
The absolute fitness is the number of
lineages (i.e. successful gametes) from
individuals from a specific genotype,
divided by the number of individuals from
the parental generation.
Absolute fitness AA = 10/2 = 5
Absolute fitness aa = 4/2 = 2
Fitness has many components – for
example AA and aa differ here in both
viability and reproductive success

40. Absolute and Relative Fitness
Example: a population of 4 individuals mate and produce offspring
Absolute fitness :
Absolute fitness AA = 10/2 = 5
Absolute fitness aa = 4/2 = 2
Relative fitness is calculated by dividing all
fitness values by the largest value (thus the
fittest genotype always has a relative fitness=1).
Relative fitness AA = 5/5 = 1
Relative fitness aa = 2/5 = 0.4
Notice that aa actually left as many descendent
genes as it had in the first generation, and yet its
relative fitness is still less than 1

41. Fitness and selection
Fitness is a property of a particular genotype. Selection is a process
(not really a ‘force’) leading to different expectations of transmitting
genes to the next generation.
• If different individuals of a population have different fitness then
we say that selection is operating.
• If they have the same fitness then we say that there is no
selection, or equivalently, that the population is evolving neutrally.
What kind of evolution might we expect to see if there was no
selection operating?...
Genetic Drift!

42. Fitness and selection
The fitness of different genotypes is often represented by the
symbol ω (omega).
• For example, the fitness of the AB genotype is often
represented by the symbol ω AB
The strength of selection is often represented by the symbol s.
• For example, if AB is not the fittest genotype then the strength
of selection against heterozygotes can be thought of as the
deficit from a relative fitness of 1, so that
ω AB = 1 – s

43. Selection and Drift Combined
• Previously we imagined that all individuals
had the same fitness
• Taking a particular individual of the offspring
generation, it was equally likely that any
member of the previous generation was the
parent.
• The effect of high fitness is to make an
individual more likely to be the parent of
offspring in the next generation
• It is still possible that a fit individual will get
unlucky and end up having no kids

44. No Selection
Happening
Genetic Drift
Look at many replicates of the process of evolution
• Equal chance of drifting up or down
• If we leave enough time we can be certain that one or other
allele will become fixed, and the other will become lost.
• Which of these events is more likely depends only on the
starting allele frequency. There is no selection in this model!

45. Selection and Drift Combined
A model in which A is dominant and has high fitness. Allele frequencies
still drift around as before, but now there is a systematic change in an
upward direction.
Notice that there is still one case in which, despite the high fitness of
individuals with the A allele, the A allele gets lost due to pure chance.

46. Deprogramming complete! You are
now (hopefully) rehabilitated.

47. Away from pan-selectionism
• Genetic drift is one of the most important
processes in evolution.
• It is not a case of choosing between selection or
drift. Selection occurs against a background of
drift.
DRSELECITIFON T

48. Announcements
• There will be a workshop in week 8 on drift. The assessment
completed during the workshop will count for 20% of your
score in this course.
• In this workshop we will use the program PopG. When
you arrive, you will be tested on your ability to use PopG.
Full details of how to access the program and what you
will be tested on will be on the course website.
• Make sure you have submitted 1 question per week of
course material on Peerwise.