Molecular Evolution

Question 1

What is Evolution?

Answer 1

On the origin of species
- A theory put forward to explain the current variety of life on earth
- Natural selection and Fitness
- Underpins our understanding of biology

Question 2

Define “Natural Selection”

Answer 2

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

Question 3

Define “Fitness”

Answer 3

How well a species is able to reproduce in its environment.

Anything that increases fitness is selected for, anything that deceases fitness is selected against and other neutral changes will vary randomly.

Question 4

Describe the modern synthesis

Answer 4

• It was realised that evolution could be linked to genetics to explain modular processes underlying evolution
• Genetic variation is the main source of heritable changes in a species
• Frequencies of genetic variants are affected by:
  Selection, Mutation, Migration, Genetic Drift

Question 5

Describe how Selection affects genetic variants

Answer 5

• Genetic variants that confer a POSITIVE advantage will be selected for (and vice versa)
• Examples of + advantages include resistant to disease, ability to metabolise new food source, antibiotic resistance.
• Some parts of the genome are resistant to change as they contain vital sequences - they are conserved

Question 6

Describe how Mutation affects genetic variants

Answer 6

• Mutation is the process by which Variation in the genome arises
• 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 risen recently or be deleterious and being selected against or both

Question 7

Describe how Migration affects genetic variants

Answer 7

• Migration is the physical movement of people from a different population which 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 8

Describe how Genetic Drift affects genetic variants

Answer 8

• 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 9

Describe Sequence Conservation

Answer 9

• DNA sequence conservation is vital to the survival of an organism. Doesn’t show much evidence of variation.
• Most variants in these regions will be selected against as they’re likely to have a strong deleterious effect.
• There is some flexibility for variation in the third base of codons as some amino acids are encoded by multiple codons.

Question 10

What are the different types of Sequence conservation in genes?

Answer 10

• High conservation - Coding regions (not exons as these contain non coding regions)
• Intermediate conservation - promoter, 5’ UTR, 3’ UTR, terminator
• Low conservation - Introns, 3rd base of codons, terminator

Question 11

What can Conservation be used for?

Answer 11

CROSS SPECIES COMPARISON
- Can be used to generate evolutionary profile for a gene or family
- Allows us to identify the important regions of a gene
- This allows us to concentrate on areas that appear to be important in novel genes

Question 12

What is Phylogenetics?

Answer 12

Phylogenetics is the study of evolutionary relationships among biological entities

Question 13

What is a phylogenetic tree? How can it be used?

Answer 13

• Has multiple diagram types
• Main aim is to illustrate the relatedness of different species or sequences
• Distance between two entities on a tree is usually related to how similar they are
• Distance is usually related to both evolutionary pressures and to time
• Time estimated by measuring mutation rates

Question 14

How has Phylogenetics been used in the past?

Answer 14

• 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 HIV
• Worobey eat al (2004) investigated this using phylogenetic

Question 15

What is gene duplication?

Answer 15

The Duplication of the DNA sequence containing a gene

Question 16

What is the typical mechanism for gene duplication?

Answer 16

The unequal crossing over during meiosis

Question 17

What happens after gene duplication?

Answer 17

• One copy can continue the original function
• The other copy can evolve new functions through changes in the coding sequence and/or control sequences.

Question 18

What is Unequal Crossing Over?

Answer 18

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

Question 19

Describe the Globin genes

Answer 19

• Has 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 20

Describe the Alpha and Beta chromosome positioning???
Check over

Answer 20

Alpha: Haemoglobins in order of production during development
Beta: Symbols are Greek letters – Zeta, Epsilon, Alpha, Gamma, Delta and Beta
Green indicates DNA control elements

Question 21

Describe the Globin Cluster Evolution

Answer 21

• Very clear that Globin genes have evolved through duplication and accumulation of mutations
• Some are functioning and some are not (Pseudogenes)
• Promoters have diverged so they bind to different transcription factors and allow expression of genes at different stages of development.
• Embryo -> Foetus -> Postnatal

Question 22

What are Pseudogenes?

Answer 22

• 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

Question 23

Sickle Cell Disease. When do the symptoms typically start?

Answer 23

Typically start at 5-6 months of age

Question 24

What are the main symptoms of Sickle Cell Disease?

Answer 24

• Anaemia: Fatigue, Restlessness, Juandice
• Acute Pain Episodes: “Crises” x due to oxygen deprivation of tissues
• Increased frequency of infections: Spleen damage

Question 25

What are the other symptoms of sickle cell disease?

Answer 25

Stroke, Pulmonary Hypertension, Gallstones, Liver and Kidney problems, Joint problems, Delayed Puberty

Question 26

Explain the genetics of Sickle Cell Disease

Answer 26

- A single base change occurs in the beta Globin gene of Haemoglobin A = Haemoglobin S (HbS) - Codon Changes from GAG to GTG - This changes the amino acid from Glu -> Val at position 6 of the protein - An autosomal recessive genetic disease - The original mutation occurred 7300 years ago

Question 27

Describe how Sickle Cell Disease is passed on through genetics

Answer 27

- If both parents have a copy of the HbS then each child has a 1 in 4 chance of having Sickle Cell Anaemia (2 copies of HbS) - Sickle trait is common in African, Middle Eastern, Mediterranean and Indian populations and very rare in Northern Europe

Question 28

Give an example of a heterozygote advantage

Answer 28

- 2ncopies 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.

Question 29

SUMMARY

Answer 29

- Mutational processes can lead to genes being duplicated - They can also lead to new functions - Evolutionary pressure can be very strong and lead to maintenance of apparently damaging variants - Malaria and HbS are good examples of this