Molecular evolution

Question 1

What two ideas is ‘the origin of species’ based on? What are the definitions?

Answer 1

Natural selection – The effect of factors that influence the frequency of heritable changes in a species. An example of a factor could be food availability and an example of the heritable change would be the ability to detect food.
Fitness – How well a species is able to reproduce in its environment. It is just about reproduction, northing else. Anything that increases fitness (hence reproduction) is selected for and anything that decreases fitness is selected against.

Question 2

What is the main source of heritable changes in a species?

Answer 2

Genetic variation. Main heritable sources = DNA/Genetics

Question 3

What are frequencies of genetic variants affected by?

Answer 3

Selection, mutation, migration, genetic drift

Question 4

What is selection? Give examples.

Answer 4

The preferential survival/elimination of organisms with certain genotypes. Genetic variants that confer a positive advantage (for a organism/species) will be selected for and vice versa.
Examples: Resistance to disease, ability to metabolise a new food source, antibiotic resistance, appearance change that enhances mate choice.

Question 5

Why are some parts of the genome resistant to selection/change?

Answer 5

However, some parts of the genome are resistant to change as they contain vital sequences – they are conserved. For example, the DNA of the active site of an enzyme will only tolerate slight changes before it becomes inactive or possibly only able to work with a different substrate

Question 6

What is mutation?

Answer 6

The process in which variation in the genome arises. Humans are all mutants – we all carry large numbers of genomic variants (compared to the rest of our species) and their frequency will depend on selection and when they first arose.
A rare variant in a population may have arisen very recently ( so rare overall) or it could be selected against (deleterious), OR Both.

Question 7

What is migration?

Answer 7

The physical movement of people/species from a different population into an existing population, which results in new pools of variants being introduced to the existing population. You may hence see an increase in a particular disease because the group that have moved in brought in a variant that causes disease in that environment.
The mixture of these two different populations is referred to as admixture. Population frequencies of specific variants can change purely due to admixture and not be disease related.

Question 8

What is Genetic drift?

Answer 8

When the frequency of variants changes in a population due to CHANCE. Not all organisms in a population will pass on their genetic variants (will only pass on half). Furthermore, mechanisms such as recombination will also result in not all variants being passed on. Hence, all variants are subject to genetic drift. Quickly drift apart in small populations compared to large ones.

Question 9

What is sequence conservation?

Answer 9

Conserved- parts of the genome that are resistant to change. Hence a conserved sequence is a nucleotide sequence in DNA or RNA, or an amino acid sequence in a protein that has remained largely unchanged during evolution- the sequence being the same/extremely similar between species. Examples include sequences in promoters, rRNA etc. In exons you get a lot of conservation, however in some parts there is little/less conservation. This may be 3rd bases (as AA’s are encoded by multiple codons) or bits that don’t need to be conserved.

Question 10

What are the different types of sequence conservation in genes?

Answer 10

• High conservation: Coding regions (not specifically exons as some exons can contain non-coding regions, e.g. the first and last exon have non-coding regions)
• Intermediate conservation: Occurs in places like promoters, 5’ UTRs, 3’UTRs, terminator
• Low conservation: Introns (splice sites), 3rd base of codons, Terminator

Question 11

What can sequence conservation be used for?

Answer 11

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 12

What is phylogenetics?

Answer 12

The study of evolutionary relationships between species

Question 13

What do phylogenetic trees show?

Answer 13

They illustrate the relatedness of different strains/species/sequences. Distance between two entities on a tree is usually related to how similar they are. Distance is related to both evolutionary pressures and to time. Time can be estimated by measuring mutation rates (so we can estimate differences in species)

Question 14

What are the globin gene clusters?

Answer 14

2a and 2b proteins- These exist alongside a whole group of other genes called gene clusters. They exist as two clusters.
Alpha like- On chromosome 16. 3 genes and 3 pseudogenes
Beta like – On chromosome 11. 5 genes and 1 pseudogene.
The genes are arranged in order of expression during development.

Question 15

What is gene duplication?

Answer 15

Duplication of a DNA sequence containing a gene. The typical method is unequal crossing over during meiosis. After duplication, we have two copies of the same gene on one chromosome. One copy can continue the original function of that gene. The other copy can evolve new functions through changes in the coding sequence and/or control sequences by mutation (possibility of related genes arising)

Question 16

What is unequal crossing over?

Answer 16

Recombination between sequences that are not the correct sequence but are very similar (non-identical but similar). Occurs often with low copy number repeat sequences. These are a series of repeats that are duplicated around the genome which match each other and so recombination can occur.

Question 17

What is the main Hb in adults? And the main fetal Hb?

Answer 17

Adults – HbA (consisting alpha and beta subunit). Postnatally, there is also HbA2 (alpha and delta)
Fetal – HbF (consisting of alpha and gamma subunit)

Question 18

How did the evolution of globin gene clusters come about?

Answer 18

Evolution of globin genes by gene duplication and divergence ( the accumulation of mutations). There are a number of variations observed from an ancestral myoglobin like molecule. We know that myoglobin is related to the rest of all the globin’s (alpha,zeta,epsilon,gamma,delta,beta) and appears to be similar to the ancestral molecule.

Question 19

What are pseudogenes?

Answer 19

Non functioning genes, that look similar to functional genes. They typically have many mutations. There are many of them in the genome. They complicate techniques such as PCR, sequencing etc.

Question 20

What are the main symptoms of SCD? What is it due to?

Answer 20

Anaemia- fatigue, restlessness, jaundice
Acute pain episodes – ‘crises’ due to oxygen deprivation of tissues
Increased frequency of infections – spleen damage
Other symptoms include stroke, pulmonary hypertension, gallstones, liver and kidney problems, joint problems, delayed puberty.
They are all due to the ‘sickling’ of red blood cells.

Question 21

What is the genetic basis of SCD?

Answer 21

It is due to a single base change (A to T) in the beta globin gene of HbA, to give Haemoglobin S = HbS. The codon change is a GAG to GTG. This is Glu to Val at position 7 of the protein.
It is an autosomal recessive genetic disease (need copy of gene from both parents). 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)

Question 22

What is the heterozygote advantage in people with SCD?

Answer 22

The two copies of HbS variant reduces reproductive ability – SCD
However, if a person has one copy of the HbS variant (hence a carrier) they have been found to confer resistance to malaria. This heterozygote advantage means that the HbS variant is maintained in the population when otherwise it would have been selected against and lost.