This document provides an overview of lectures for Week 6 on the genetic basis of evolution. The lectures will cover general introductions, defining key terms, genetic drift, and natural selection. Students are advised to read additional material on evolution. The lectures aim to move students away from overly simplistic "pan-selectionist" views and help them understand how genetic drift and natural selection both shape evolution. Genetic drift, the random changes in allele frequencies due to chance events in small populations, is a major factor in evolution and occurs in all populations.
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”
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.
9. Defining our Terms, Part I
We need to understand the following vocabulary, so that
we can use the words accurately and confidently:
1)
2)
3)
4)
5)
Gene
Locus
Allele
Genotype
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)
MYCN is an important oncogene in Neuroblastoma: an embrional cancer like
retinoblastoma and nephroblastoma (Wilms tumor). The precursor cell is an
undiferentiated neuroblast from the neural crest. It is a true pediatric disease with the
median age of diagnosis less than 2 years.
13. Definition: Locus
This figure shows a FISH experiment: with 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)
2×Homozygotes + Heterozygotes
Frequency of A allele:
p = 11/16 = 0.6875
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 HardyWeinberg 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)
7)
8)
9)
Gamete
Zygote
Dominant
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
24. 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 can be found on the course website.
PLEASE READ THESE DETAILS
•
Please find out which session you are in:
–
–
–
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
26. 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.
27. 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.
28. 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.
29. 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 has drifted from one
generation to the next.
30. Genetic Drift
Graph of a particular allele frequency as it changes over time
(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 our 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.
It turns out that these modifications make very little difference to the
process of drift! The key fact is always true:
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 genes at the same
stage of the life cycle in the next generation.”
High
Low
fitness?
fitness?
I will use ‘fitness’ to mean a property of genotypes
– not alleles or even phenotypes.
39. Absolute and Relative Fitness
Take the following example, in which a population of just 4 individuals
mate and produce offspring
The absolute fitness is the number of offspring 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
Take the following example, in which a population of just 4 individuals
mate and produce offspring
Relative fitness is calculated by dividing all fitness
values by the largest value, meaning the fittest genotype
always has a relative fitness of 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 w (omega).
– For example, the fitness of the AB genotype is often
represented by the symbol wAB
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
wAB = 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. 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.
45. Away from pan-selectionism
Deprogramming complete! You are now (hopefully) rehabilitated.
• 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.
QUESTIONS?
46. 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 can be found on the course website.
PLEASE READ THESE DETAILS
•
Please find out which session you are in:
–
–
–
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