The Genetic Basis of Evolution

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

Lecture Outline

1) General Introduction

2) Defining our Terms

3) Genetic Drift

4) Selection

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

Away from pan-selectionism

“Then the elephant sat back on his little haunches, and pulled, and pulled, and pulled, and his nose began to stretch”

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

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

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.

DRIFTSELECTION

Lecture Outline

1) General Introduction

2) Defining our Terms

3) Genetic Drift

4) Selection

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

Definition: GeneGene

• 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

Definition: LocusLocus (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]

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)

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.

Definition: AlleleAllele

• 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)

Definition: GenotypeGenotype

• The genetic makeup of an individual • A description of the alleles possessed by an individual

Genotype frequency

Under random mating we expect to see Hardy-Weinberg genotype frequencies:

p2 2p(1-p) (1-p)2

0.5 0.375 0.125

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!

Definition: PhenotypePhenotype

• 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?

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

Definition: Gamete & ZygoteGamete

• 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

Definition: Dominant & RecessiveWhich 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)

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.

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

Questions?

Lecture Outline

1) General Introduction

2) Defining our Terms

3) Genetic Drift

4) Selection DRIFT

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.

Genetic DriftHow 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.

Genetic DriftWe 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.

Genetic Drift: ExampleTwo 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.

!

Simulation starting with 100 heterozygous individuals

(p=0.5)

Genetic DriftGraph of a particular allele frequency as it changes over time

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)

(population size = 100 diploids)

Genetic DriftLook 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!

Think about it….

!

Would genetic drift be stronger in a smaller population or a larger population?

Genetic DriftGenetic 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

!

Genetic DriftOne 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

!

Genetic DriftAt the moment our model of how a population evolves is an extremely simplified cartoon of real life. We could make it more realistic by…

These modifications make very little difference to the process of drift! The key fact is always true:

• 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.

Lecture Outline

1) General Introduction

2) Defining our Terms

3) Genetic Drift

4) Selection DRIFTSELECTION

Defining FitnessWe 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? !

Defining FitnessThe 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.

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.

Calculating/Estimating Fitness

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

Absolute and Relative Fitness

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

Absolute fitness :Absolute fitness AA = 10/2 = 5 Absolute fitness aa = 4/2 = 2

Example: a population of 4 individuals mate and produce offspring

Fitness and selectionFitness 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!

Fitness and selectionThe 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

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

Genetic DriftLook 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!

No Selection Happening

Selection and Drift CombinedA 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.

Deprogramming complete! You are now (hopefully) rehabilitated.

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.

DRIFTSELECTION

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.