6. Host-Pathogen Co-Evolution Flashcards
Structure of the lecture
- The Matching-Alleles framework is a subset of the Gene-For-Gene framework
- Immune selection shapes population structure of pathogensd, such as in MHC loci
- The future of Immune selection research
Describe the matching alleles framework
1.1
Matching Alleles: Pathogens require an exact genetic match to the host for infection, which leads to highly dynamical infection. Agrawal and Lively, 2002.
Shown in Pasteuria ramosa infection of Daphnia magna. **Decaestacker et al., 2007 **. Modelled rapid co-evolutionary dynamics in natural settings using a negative frequency-dependent selection model. Found exchange of fitness in the system. Pathogens were best adapted to CURRENT VERSIONS OF THE HOST. Steady increase in pathogen virulence over time, associated with host fitness
Describe the Gene-for-Gene continuum
1.2
Gene-for-Gene: One pathogen genotype has broad host range , leading to a Red-Queen co-evolutionary arms race
Shown in norovirus co-evolution with human blood group antigens. Currier et al., 2015 found that the FUT2 secretor genotype strongly influences susceptibility to certain norovirus strains, particularing in GII.2 strains. De Rougemont et al., 2011 showed that different temporal variations of NoV strains are associated with different FUT2 secretor genotypes
How did Ashby and Boots resolve the Matching Alleles/Gene-For-Gene beef?
1.3
Showed that the gene-for-gene continuum CONTAINS the matching-alleles framework as a subset
(MA nested with GFG)
Matching alleles framework can only generate one mode of fluctuating selection, whereas Gene-for-Gene produces rapid ‘within-range’ and slower ‘between-range’ cycles
What did Gupta et al., 1999 suggest about immune selection and pathogen populations?
2.1
Immune selection can shape the population structure of pathogens
Use of mathematical models to combine population genetic and epidemiological processes
Shows that non-random associations between epitope regions can be used as a new strategy to identify dominant polymorphic antigens
What did Penman et al., 2013 show about immune selection and pathogen behaviour?
2.2
Pathogenic behaviour can emerge as a result of immune selection
There are 3 different options for this
- Pathogens can adopt of permanent, non-overlapping strain structure that drives host-alleles to complete linkage disequilibrium
- Pathogen strain structures can cycle from one state to another, causing host-alleles to do the same
- Non-overlapping associations between MHC loci could be the result of pathogen selection (best argument)
How did Mehra and Kaur (2004) show host-pathogen co-evolution?
2.3
MHC co-evolution with HIV
Understanding the particular MHC HLA expressed by a particular geographic population is important
These are likely to determine which HIV epitopes are immunodominant
Can be used for MHC-based vaccine design
How did Barquera et al., 2014 show host-pathogen co-evolution in ancient Mayan population?
2.4
Non-overlapping MHC associations in Mayan populations
Comparison of MHC loci in Ancient Mayan populations and Present-Day Mayan descendants.
Found potential adaptation of MHC locu due to infectious diseases brought across from the colonial period
How have selective pressures influenced the population dynamics of KIRS?
2.5
Parham et al., 2005: raised possibility that the interplay between KIRS and MHCI Polymorphisms has facilitated human survival during epidemics
Parham and Moffat, 2013, found that foetal HLA genotypes and maternal KIRS genotypes combine to influence risk of pre-eclampsia and birth weight risks
Penman et al., 2016 shows that wee need to incorporate understanding of selection to model infection and survival
How can we begin to uncover new infection resistant loci?
3
- Case-control studies (using Odds Ratio to compare infected/control individuals. Success in modelling HLA and malaria/HIV)
- GWAS. Studying whole genome and SNP library. Used to model Dantu phenotype
