Recombination and Multigene Evolution

Question 1

How is genetic variation maintained in a population

Answer 1

Balancing selection (overdominanc and frequency dependent selection)
Mutation-drift balance
Migration-drift balance (and hybridisation, genetic introgressions)

Question 2

What dos MHC stand for

Answer 2

Major Histocompatibility Complex

Question 3

What is the MHC

Answer 3

The MHC is a gene dense region that is present in all jawed vertebrates which harbours immune gene that encode for proteins involved in antigen presentation

Question 4

What does the MHC play important biological functions in

Answer 4

resistance to infectious,

individual odours, mating preferences, kin recognition and reproductive success

Question 5

Where are the most polymorphic genes in the vertebrate genome

Answer 5

MHC

Question 6

What is the main characteristic of the MHC

Answer 6

strong linkage disequilibrium

Question 7

What is linkage disequilibrium

Answer 7

Linkage disequilibrium refers to the non-random association of alleles at two or more loci in a general population. When alleles are in linkage disequilibrium, haplotypes do not occur at the expected frequencies.

Question 8

What two types of balancing selection have been proposed to explain the MHC

Answer 8

Overdominance model (heterozygous superiority)
Negative frequency dependent selection model

Question 9

What are the 3 main question surrounding the MHC

Answer 9

How can selection maintain high levels of polymorphism in small populations?
How can balancing selection maintain MHC alleles over long evolutionary time (trans-species polymorphism)?
Why is the MHC is linked to so many diseases?

Question 10

How does the MHC present itself in small, bottlenecked populations

Answer 10

MHC has a high level of diversity which neutral genetic marker loci have very low diversity

Question 11

What is trans-species polymorphism?

Answer 11

is the occurrence of similar alleles in related

species

Question 12

What dos polymorphic mean?

Answer 12

discontinuous genetic variation

Question 13

What pairs share identical MHC alleles

Answer 13

Guppies and P. picta and humans and chimps

Question 14

Why is it strange that identical MHC sequences have been found in distantly-related species

Answer 14

because host-parasite coevolution and Red Queen arms race predict a fast turnover of alleles

Question 15

What pathlogies are associated with the MHC in humans

Answer 15

psoriasis, rheumatoid arthritis, insulin-dependent diabetes, autoimmune disorders

Question 16

What can you conclude from the observation that ‘MHC has a strong haplotype block structure’

Answer 16

Epistasis must be strong
Positive epistasis between immune genes that operate well together
Negative epistasis between bad mutations

Question 17

What can you conclude from the observation that ‘many disease mutations in the MHC

Answer 17

Faster mutation rate
More important genes that can cause disease
Less efficient selection against mutations

Question 18

What could cause the less efficient selection against mutations in the MHC

Answer 18

There must be benefits from those mutations (antagonistic pleiotropy)
Mutations do not get often expressed (are rare and recessive, which mean they are ‘sheltered’ by a healthy wild type allele)

Question 19

What is Muller’s ratchet and what does it cause

Answer 19

the accumulation of mutations in asexuals. Mutations can become fixed because without recombination, purifying selection is inefficient.

Question 20

What does genetic hitchhiking do to genetic variation

Answer 20

reduces genetic variation because the ‘fate’ of polymorphisms depends on selection on nearby genes.

Question 21

What is epitasis

Answer 21

The masking of the phenotypic effect of alleles at one gene by alleles of another gene e.g albinism

Question 22

What dos ABC stand for

Answer 22

Associated Balanced Complexes

Question 23

What are ABCs

Answer 23

Recessive deleterious mutations accumulate in linkage blocks in haplotypes

Question 24

In ABC theory, what type of selection is occuring on the MHC

Answer 24

Selection on the MHC is overdominance (on the immune genes) and purifying selection (on the linked mutations)

Question 25

What do the current models say about the MHC

Answer 25

Current models (overdominance, frequency dependence) suggest that balancing selection acts on a single gene only

Question 26

Key features of ABC evolution

Answer 26

Accumulation of recessive deleterious mutations in MHC haplotype blocks in a process similar to Muller’s ratchet These mutations are potentially disease causing They furthermore define the haplotype block structure by epistatic selection against recombinants Selection against mutations is strong when haplotype block becomes common, which retains homogeneous allele frequency (and polymorphism) in the population This selection can also work without selection on the actual immune gene

Question 27

What was Aguilar et al 2004 theory about MHC diversity

Answer 27

They argued the MHC diversity is maintained by balancing selection, with MHC loci having a selection coefficient greater than 0.5

Question 28

what did the original over dominance model state

Answer 28

overdominance model states that polymorphism is | maintained because heterozygous individuals are able to recognize a wider variety of parasites

Question 29

What was originally thought to maintain the high level of polymorphsim in the MHC

Answer 29

Selection by parasites and sexual | selection

Question 30

what does negative frequency-dependent | selection model assumes that

Answer 30

The negative frequency-dependent selection model assumes that, because selection favours parasites that can avoid recognition by the most common MHC variants, rare MHC alleles offer better parasite resistance

Question 31

When is the MHC polymorphism prone to erosion

Answer 31

when there is little or no parasite selection, MHC polymorphism is prone to erosion by random genetic drift, particularly in small populations.

Question 32

What is the issue with traditional model of balancing selection on the MHC when assuming parasites are the only agent of selection

Answer 32

often require unrealistically large selection coefficients | (SR0.2) to explain the observed MHC polymorphism in small populations

Question 33

what does the fact that the MHC's islands of high linkage disequilibria (LD) interspersed by recombination hot spots suggest is happening

Answer 33

epistasis and genetic hitch-hiking

Question 34

what does the traditional balancing selection models not consider

Answer 34

ignores the potential role of linkage and epistatic | gene–gene interactions.

Question 35

What did the ABC model propose

Answer 35

recessive disease-causing mutations can accumulate in the MHC in a process similar to Muller’s ratchet Natural selection fails to purge these mutations because this so-called ‘sheltered load’ only rarely becomes expressed, given the large number of MHC alleles and high gene diversity

Question 36

What reduces the effective rate of recombination in the MHC

Answer 36

``` functional epistasis and haplotype block (haploblock) structure ```

Question 37

How does Muller's ratchet affect the MHC

Answer 37

Because there is reduced recombination, mutations are less effectively removed

Question 38

What reduces the selection effectiveness at removing mutation from the MHC

Answer 38

the reduced effective rate of recombination and the typically has a high gene diversity and large number of alleles which makes it rare for bad alleles to be shown in the homozygous form