molecular evolution

Question 1

What is molecular evolution?

Answer 1

• Charles Darwin (1859)
• based on natural selection and fitness
• explains the current variety of life on earth

Question 2

What is natural selection?

Answer 2

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

Question 3

What is fitness?

Answer 3

• how well species are able to reproduce in its environment.

- anything that increases fitness is selected.

Question 4

what is modern synthesis theory?

Answer 4

• theory that explains evolution could be unified with genetics to explain the molecular process underlying evolution.
• genetic variation is the main source of heritable changes in a species.

Question 5

what factors affect frequencies of genetic variants?

Answer 5

• selection
• mutation
• migration
• genetic drift

Question 6

What is selection?

Answer 6

-genetic variants that confer a positive advantage will be selected for, and vice versa.

Question 7

give examples of variants that confer a positive advantage in selection.

Answer 7

-resistance to disease
-ability to metabolise a new food source
antibiotic resistance
-change in appearance that enhances mate chance.

Question 8

Why are some parts of the genome resistant to change, give an example?

Answer 8

• Some parts of genome are resistant to change because they contain vital sequences which need to be conserved.
• Example : DNA that encodes active site of enzyme
• conserved = dont change through time

Question 9

Define mutation

Answer 9

• process by which variation in the genome arises
• genomic variants and their frequency depends on selection and when they first arose.
• a rare variant may arise due to base deletion(because it is disadvantageous) and being selected against.

Question 10

Define migration.

Answer 10

• physical movement of people from different population results in new pools of variant being introduced to an existing population (admixture).
• change in population can be due to admixture, not always due to disease.

Question 11

Define genetic drift.

Answer 11

• how frequency of a variant changes in a population due to chance.
• not all organisms in population will pass on their genetic variant (one gene from each parent not both)
• recombination will also result in not all variants being passed on
• all variants are subject to genetic drift

Question 12

What is sequence conservation?

Answer 12

• 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 strongly deleterious effect.(disadvantage)
• flexibility for sequence conservation due to the variation in the third base of a codon codes for same amino acid, so same protein will be coded.

Question 13

What are 3 levels of conservation?

Answer 13

• high conservation : coding regions (not exons as these contain non-coding regions)
• intermediate conservation - prometer, 5’ untranslated region (UTR), 3’ UTR, terminator.
• low conservation : introns, 3rd base of codons , terminator.

Question 14

What can we use sequence conservation for?

Answer 14

1. cross species comparison : generate an evolutionary profile for a gene or gene family
2. cross -species conservation allows us to identify the important regions of a gene (and its protein)

Question 15

Define phylogenetics

Answer 15

‘tree of life’

-incorporates all living things on earth and tries to show their relatedness in terms of evolution.

Question 16

what are 4 steps of studying phylogenetics?

Answer 16

1. observe sequence
2. reconstruct evolutionary history
3. learn more about evolutionary processes
4. develop better evolutionary models.

Question 17

What does the distance between two entities on the tree show?

Answer 17

• how similar they are
• distance is related to evolutionary pressures and time.
• time is estimated by mutation rate

Question 18

what are uses of phylogenetic in disease?

Answer 18

• it had been theorised that HIV had been introduced to human population via a contaminated polio vaccine in Africa.
• Worobey et al (2004) investigated this using phylogenetic
• sampled HIV and SIV of humans and chimpanzees
• found : polio vaccine does not give HIV bc evolutionary distance

Question 19

What is unequal crossing over?

Answer 19

recombination between sequences are not the correct sequence but are very similar
-often low copy number repeat sequence

Question 20

Give an example of globin gene.

Answer 20

• two clusters

- alpha like and beta like

Question 21

What chromosome are alpha like and beta like genes found?

Answer 21

• alpha like are on chromosome 16- 3 genes and 3 pseudogenes

- beta like are on chromosome 11 - 5 genes and 1 pseudogene

Question 22

What order are globin genes arranged?

Answer 22

• genes are arranged in the order of expression during development.

Question 23

What are pseudo genes?

Answer 23

• non functioning genes that look similar to functioning genes but are non functioning.
• complicate PCR/sequencing

Question 24

What are symptoms of sickle cell disease?

Answer 24

anaemia - fatigue, restlessness, jaundice
- acute pain episode
increased frequency of infection - spleen damage

Question 25

What is the genetics of sickle cells?

Answer 25

- a single base change in the beta -globin gene haemoglobin - codon change is a GAG to GTG - this is Glu to Val in position 6 - on chromosome 11 - autosomal recessive gene

Question 26

What is the chance of a child having SCD if parents have one copy of the the gene (Ss)?

Answer 26

1/4 chance of child having 2 copies = sickle cell

Question 27

Why is sickle cell more common in African, middle eastern and Indian population?

Answer 27

natural selection and sickle cell: - two copies has extremely negative effects on reproductivity (bc it causes sickle cell disease) - one copy of HbS variant helps resistance of severe malaria - this heterozygous advantage means that HbS variant is maintained in the population when it would have otherwise been selected against.

Question 28

What does hemoglobin consist of?

Answer 28

- 2 alpha proteins | - 2 beta proteins

Question 29

Define gene duplication.

Answer 29

- duplication of a DNA sequence consisting a gene.

Question 30

What causes gene duplication?

Answer 30

- the typical mechanism is unequal crossing over during meiosis

Question 31

What happens after duplication?

Answer 31

- one copy can continue the original function | - the other copy can evolve new functions through changes in the coding sequence and control sequences.

Question 32

What does globin cluster evolution show?

Answer 32

- globin genes have evolved through duplication and accumulation of mutations (divergence) - some are functioning genes and some are pseudogenes - divergence of promoters has occured so they bind different transcription factors and allow expression of genes at different stages of development (embryo > feotus > postnatal) .