Recombination and Multigene Evolution Flashcards
How is genetic variation maintained in a population
Balancing selection (overdominanc and frequency dependent selection) Mutation-drift balance Migration-drift balance (and hybridisation, genetic introgressions)
What dos MHC stand for
Major Histocompatibility Complex
What is the MHC
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
What does the MHC play important biological functions in
resistance to infectious,
individual odours, mating preferences, kin recognition and reproductive success
Where are the most polymorphic genes in the vertebrate genome
MHC
What is the main characteristic of the MHC
strong linkage disequilibrium
What is linkage disequilibrium
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.
What two types of balancing selection have been proposed to explain the MHC
Overdominance model (heterozygous superiority) Negative frequency dependent selection model
What are the 3 main question surrounding the MHC
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?
How does the MHC present itself in small, bottlenecked populations
MHC has a high level of diversity which neutral genetic marker loci have very low diversity
What is trans-species polymorphism?
is the occurrence of similar alleles in related
species
What dos polymorphic mean?
discontinuous genetic variation
What pairs share identical MHC alleles
Guppies and P. picta and humans and chimps
Why is it strange that identical MHC sequences have been found in distantly-related species
because host-parasite coevolution and Red Queen arms race predict a fast turnover of alleles
What pathlogies are associated with the MHC in humans
psoriasis, rheumatoid arthritis, insulin-dependent diabetes, autoimmune disorders
What can you conclude from the observation that ‘MHC has a strong haplotype block structure’
Epistasis must be strong
Positive epistasis between immune genes that operate well together
Negative epistasis between bad mutations
What can you conclude from the observation that ‘many disease mutations in the MHC
Faster mutation rate
More important genes that can cause disease
Less efficient selection against mutations
What could cause the less efficient selection against mutations in the MHC
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)
What is Muller’s ratchet and what does it cause
the accumulation of mutations in asexuals. Mutations can become fixed because without recombination, purifying selection is inefficient.
What does genetic hitchhiking do to genetic variation
reduces genetic variation because the ‘fate’ of polymorphisms depends on selection on nearby genes.
What is epitasis
The masking of the phenotypic effect of alleles at one gene by alleles of another gene e.g albinism
What dos ABC stand for
Associated Balanced Complexes
What are ABCs
Recessive deleterious mutations accumulate in linkage blocks in haplotypes
In ABC theory, what type of selection is occuring on the MHC
Selection on the MHC is overdominance (on the immune genes) and purifying selection (on the linked mutations)
What do the current models say about the MHC
Current models (overdominance, frequency dependence) suggest that balancing selection acts on a single gene only
Key features of ABC evolution
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
What was Aguilar et al 2004 theory about MHC diversity
They argued the MHC diversity is maintained by balancing selection, with MHC loci having a selection coefficient greater than 0.5
what did the original over dominance model state
overdominance model states that polymorphism is
maintained because heterozygous individuals are able to recognize a wider variety of parasites
What was originally thought to maintain the high level of polymorphsim in the MHC
Selection by parasites and sexual
selection
what does negative frequency-dependent
selection model assumes that
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
When is the MHC polymorphism prone to erosion
when there is little or no parasite selection, MHC polymorphism is prone to erosion by random genetic drift, particularly in small
populations.
What is the issue with traditional model of balancing selection on the MHC when assuming parasites are the only agent of selection
often require unrealistically large selection coefficients
(SR0.2) to explain the observed MHC polymorphism in small populations
what does the fact that the MHC’s islands of high linkage disequilibria (LD) interspersed by recombination hot spots suggest is happening
epistasis and genetic hitch-hiking
what does the traditional balancing selection models not consider
ignores the potential role of linkage and epistatic
gene–gene interactions.
What did the ABC model propose
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
What reduces the effective rate of recombination in the MHC
functional epistasis and haplotype block (haploblock) structure
How does Muller’s ratchet affect the MHC
Because there is reduced recombination, mutations are less effectively removed
What reduces the selection effectiveness at removing mutation from the MHC
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
