Molecular Evolution

Question 1

Define natural selection.

Answer 1

Natural selection- the effects of a wide range of factors on the frequency of heritable changes in a species
Fitness- how well a species is able to reproduce in environment
Anything that increases fitness is selected for, anything that decreases fitness is selected against and other neutral changes will vary randomly

Question 2

What are frequencies of genetic variants affected by?

Answer 2

Selection
Mutation
Migration
Genetic drift

Question 3

What is meant by selection, give an example. How does it relate to genes

Answer 3

Genetic variants that confer a positive advantage will be selected for (and vice versa)
Examples might confer resistance to disease, an ability to metabolise a new food source, antibiotic resistance, or a change in appearance that enhances mate choice
Some parts of the genome are resistant to change as they contain vital sequences – they are conserved

Question 4

What is meant by mutation? How does it relate to genetics?

Answer 4

The name for the process by which variation in the genome arises is mutation
We all carry large numbers of genomic variants and their frequency will depend on selection and when they first arose
A rare variant may have arisen very recently or be deleterious and being selected against or both

Question 5

What is meant by migration? How does it relate to genes?

Answer 5

The physical movement of people from a different population results in new pools of variants being introduced to an existing population
This is called admixture
Population frequencies of specific variants can change purely due to admixture and not be disease-related.

Question 6

What is meant by genetic drift? How does it relate to genes?

Answer 6

This is how the frequency of a variant changes in a population due to chance
Not all organisms in a population will pass on their genetic variants
Mechanisms such as recombination will also result in not all variants being passed on
All variants are subject to genetic drift

Question 7

What is meant by sequence conservation?

Answer 7

DNA sequence that is vital to the survival of an organism does not normally show much evidence of variation
Most variants in these regions will be selected against as they are likely to have a strongly deleterious effect
There is some flexibility for variation in the third base of codons as some amino acids are encoded by multiple codons

Question 8

What are some areas of high conservation and areas of low conservation?

Answer 8

High conservation – in coding regions (not exons as these contain non-coding regions)
Intermediate conservation – in promoters, 5’ untranslated region (UTR), 3’ UTR, terminator
Low conservation – seen in introns, 3rd base of codons, the bulk of the terminator region

Question 9

What can we use sequence conservation for?

Answer 9

Cross-species comparison can be used to generate an evolutionary profile for a gene or gene family
Cross-species conservation allows us to identify the important regions of a gene (and its protein)
This allows us to concentrate on areas that appear to be important in novel genes

Question 10

What is phylogenetics?

Answer 10

The history of our genome

Question 11

What is the purpose of phylogenetic trees and how do they work?

Answer 11

Many different types of diagrams can be referred to as phylogenetic trees but the main aim is to illustrate the relatedness of different species/strains/sequences
Distance between two entities on a tree is usually related to how similar they are
Distance is normally related to both evolutionary pressures and to time
Time estimated by measuring mutation rates

Question 12

What happens during gene duplication?

Answer 12

This is duplication of a DNA sequence containing a gene
The typical mechanism is unequal crossing over during meiosis
After duplication:
- One copy can continue the original function
- The other copy can evolve new function(s) through changes in the coding sequence and/or control sequences

Question 13

What is unequal crossing over?

Answer 13

Recombination between sequences that are not the correct sequence but are very similar
Often low copy number repeat sequences

Question 14

What are the globin gene clusters?

Answer 14

Two clusters

Alpha-like are on chromosome 16 – 3 genes and 3 pseudogenes

Beta-like are on chromosome 11 – 5 genes and 1 pseudogene

The genes are arranged in order of expression during development.

Symbols are Greek letters- zeta, epsilon, alpha, gamma, delta and beta

Green indicates DNA control elements

Question 15

How does globin gene expression vary as a fetus ages?

Answer 15

Question 16

How have globin gene clusters evolved?

Answer 16

Very clear that globin genes have evolved through duplication and accumulation of mutations (divergence)

Some are functioning genes and some are not (pseudogenes, genes that look similar to functional genes but are non-functional)

Divergence of promoters has occurred so they bind different transcription factors and allow expression of genes at different stages of development (Embryo->Foetus->Postnatal)

Question 17

What are pseudogenes and why do they exist?

Answer 17

After gene duplication, one gene can maintain the original function and the other can diverge

Pseudogenes typically have many mutations and are non-functional

There are many of them in the genome thought to be because they can lead to other functions and can be mutated without many problems like functional genes

They complicate PCR/sequencing/etc!

Question 18

Describe the characteristics of sickle cell disease.

Answer 18

Symptoms typically start at 5-6 months of age (why?)

The main symptoms of SCD are:

Anaemia – fatigue, restlessness, jaundice

Acute pain episodes – “crises” – due to oxygen deprivation of tissues

Increased frequency of infections – due to spleen damage

Also increases chances of stroke, pulmonary hypertension, gallstones, liver and kidney problems, joint problems, delayed puberty

Question 19

How does sickle cell disease happen genetically and why is it more common in those of African, Middle Eastern and Egyptian origin?

Answer 19

A single base change in the beta-globin gene of Haemoglobin A = Haemoglobin S (HbS)

Codon change is a GAG to GTG

This is a Glu->Val at position 7 of the protein

It is an autosomal recessive genetic disease

The original mutation occurred ~7300 years ago

If both parents have one copy of HbS then each child has a 1 in 4 chance of having sickle cell anaemia (two copies of HbS)

Sickle trait is common in African, Middle Eastern, Mediterranean and Indian populations and very rare in Northern Europe

Why? Because one copy of HbS leads to a resistance to malaria