Molecular Evolution

Question 1

What does the origin of species underpin?

Answer 1

Natural Selection and Fitness

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

What increases and decreases fitness?

Answer 3

How well a species is able to reproduce in its environment

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

Question 4

What factors are genetic variants affected by?

Answer 4

Selection
Mutation
Migration
Genetic Drift

Question 5

What is selection?

Give some xamples

Are sequences conserved?

Answer 5

• 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 6

What is mutation?

What do we all carry?

Answer 6

• 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 7

What is migration (admixture)?

Answer 7

• 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 8

What is genetic drift?

Do all organism pass on genetic variants? why?

Are all organism subject to genetic drift?

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

Does a DNA sequence vital to an organism survival show much evidence of variation?

Are they selected for?

Why is there flexibility in the third base codon?

Answer 9

• 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 10

What are high, intermediate and low conservation genes?

Answer 10

• High conservation – coding regions (not introns as these contain non-coding regions)
• Intermediate conservation – Promoter, 5’ untranslated region (UTR), 3’ UTR, terminator
• Low conservation – introns, 3rd base of codons, terminator

Question 11

Give some examples of conservation

Answer 11

• NAMPT is Nicotinamide phosphoribosyltransferase
• Diagram shows intron 6, exon7 and intron 7
• Vertical black lines show sequence conservation with other species
• Cons-100-vert – measure of conservation – higher = higher conservation

Question 12

What can we use sequence conservation (cross-species comparison) for?

Answer 12

• 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 13

What is a phylogentic tree?

Describe the distance in a tree?

How is time estimated?

Answer 13

• Many different types of diagram 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 14

Read about HIV and polio

Answer 14

On document - page 3

Question 15

How many chains has haemoglobin got and how many gene clusters?

Answer 15

• 2 alpha and 2 beta chains

* Exist with other genes in 2 gene clusters

Question 16

What is gene duplication?

Answer 16

• This is duplication of a DNA sequence containing a gene

* The typical mechanism is 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 function(s) through changes in the coding sequence and/or control sequences

Question 18

Describe unequal crossing over

Answer 18

On document - page 3

Question 19

Where are the alpha and beta linked genes for haemoglobin found?

Answer 19

• Alpha-like are on chromosome 16 – 3 genes and 3 pseudogenes (later on discussed)
• 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 development of haemoglobin and expression

Answer 20

On image

Question 21

Have a look at the evolution of the globin gene clusters

Answer 21

Evolution by gene duplication and divergence

Question 22

How have globin gene clusters evoled?

Are all the genes function?

What does divergence of promoters allow?

Answer 22

• 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 23

What are Pseudogenes

Answer 23

• 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 24

What are the main symptoms of sickle cell?

Answer 24

• 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 25

Describe the genetics of sickle cell

Answer 25

• 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? = DUE TO NATURAL SELECTION AS EXPLAINED BELOW

Question 26

• Sickle trait is common in African, Middle Eastern, Mediterranean and Indian populations and very rare in Northern Europe WHY? = DUE TO NATURAL SELECTION AS EXPLAINED BELOW

Answer 26

• 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.