molecular evolution

Question 1

Natural selection

Answer 1

The effects of a wide range of factors on the frequency of heritable changes in a species

Question 2

Fitness

Answer 2

How well a species is able to reproduce in its environment

Question 3

The link between evolution and genetics

Answer 3

Evolution with genetics can help explain the molecular process underlying evolution.

Question 4

Frequencies of genetic variants are affected by

Answer 4

Selection, Mutation, migration, genetic drift

Question 5

Selection

Answer 5

Genetic variants that confer a positive advantage will be selected for (vice versa)

Question 6

Example of selection

Answer 6

Confer resistance to disease, an ability to metabolise a new food source, antibiotic resistance or a change in appearance that enhances mate choice

Question 7

Anomalies with selection

Answer 7

• Some parts of the genome are resistant to change as they contain vital sequences – they are conserved

Question 8

Mutation

Answer 8

• 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 9

Migration

Answer 9

• 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 10

Genetic drift

Answer 10

• 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 11

Sequence conservation

Answer 11

• 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 12

High conservation

Answer 12

coding regions (not exons as these contain non-coding regions)

Question 13

Intermediate conservation

Answer 13

Promoter, 5’ untranslated region (UTR), 3’ UTR, terminator

Question 14

Low conservation

Answer 14

Introns, 3rd base of codons, terminator

Question 15

What can we use sequence conservation for?

Answer 15

• 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 16

Main phylogenetic trees

Answer 16

• 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 releated to both evolutionary pressures and to time
• Time estimated y measuring mutation rates

Question 17

Infectious disease and phylogenetics

Answer 17

• It had been theorised that HIV had been introduced to some of the human population via a contaminated polio vaccine in Africa
• Some polio vaccines used to be produced using cultured chimpanzee cells, which could have been infected with SIV

Question 18

HIV and polio vaccine

Answer 18

• The tree demonstrates that the SIV genome in DRC wild chimpanzees was completely distinct from all HIV genomes
• Other SIV strains were likely to be the source as they are closely related to HIV

Question 19

What is gene duplication?

Answer 19

• This is duplication of a DNA sequence containing a gene

* The typical mechanism is unequal crossing over during meiosis

Question 20

What happens after duplication

Answer 20

• 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 21

Unequal crossing over

Answer 21

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

Question 22

Globin genes

Answer 22

2 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.

Question 23

What are the greek letters

Answer 23

Zeta, Epsilon, Alpha, Gamma, Delta and Beta

Question 24

Globin gene expression

Answer 24

Hb F (fetal) - high alpha, high gamma. Early on, high epsilon and zeta

Hb A (after birth) - alpha, beta, low gamma, low delta

Question 25

Globin cluster evolution

Answer 25

* Very clear that globin genes have evolved though duplication and accumulation of mutations (divergence) * Some are functioning genes and some are not (pseudogenes) * 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 26

Pseudogenes

Answer 26

* 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 * They complicate PCR/sequencing/etc!

Question 27

Sickle cell disease symptoms

Answer 27

Symptoms typically start 5-6 months of age • Anaemia – fatigue, restlessness, jaundice • Acute pain episodes – “crises” – due to oxygen deprivation of tissues • Increased frequency of infections – spleen damage • Also stroke, pulmonary hypertension, gallstones, liver and kidney problems, joint problems, delayed puberty

Question 28

Codon change for Sickle cell gene

Answer 28

GAG - GTG | Glu > Val at position 7 of the protein

Question 29

What type of genetic disease is sickle cell disease?

Answer 29

Autosomal recessive genetic disease

Question 30

When was the original mutation for sickle cell disease

Answer 30

7300 years

Question 31

Where is sickle cell common?

Answer 31

African, middle eastern, Mediterranean and Indian populations and very rare in northern Europe

Question 32

Why is sickle cell common in these areas?

Answer 32

* Two copies of the HbS variant has significant negative effects on reproductive ability - SCD * However, one copy of the HbS variant confers resistance to severe malaria * This “heterozygote advantage” means that the HbS variant is maintained in the population when otherwise it would have been selected against and lost.