HP Modularity

Host-Pathogen Modularity

This is the working space for our project. Everything written is a work in progress.

Title Ideas

• Evolution of modularity in a host-pathogen system
• Modularity: a pathogen's answer to host interactions
• Do host-pathogen interactions lead to the adaptive evolution for modularity?
• more here

Major Questions

1. Does modularity in pathogen genes responsible for an interaction with a host increase its ability to adapt to a host?
2. under what conditions does pathogen modularity arise? specifically,
   1. Is modularity in the host required?
   2. what configurations of the interaction matrix?
   3. what influence does population structure have (in the hosts)?
3. additional ones here

Questions to answer in proposal

1. why are we studying host-pathogen interactions?
2. what evidence suggests that modular allelic dependencies might be advantageous in such a host-pathogen system?
3. give a one-line description of this type of modularity
4. what conditions do we aim to test to show a benefit to modular dependencies/interaction structures?
5. what are our null models, i.e. why is (this) result a surprise?
6. what impact does this have for the understanding of host-pathogen interactions, and evolvability in general?

Proposal Introduction

While interactions between species such as hosts and their pathogens (or plants and pollinators, herbivores and plants) have long been implicated as a means of generating patterns of diversification (Ehrlich and Raven 1964; Thompson 1994, 2005), the process by which forces generate robustness and evolvability is not well understood for coevolutionary systems. Previous authors (citation) have suggested that environmental variation leading to temporal changes in fitness can select for modularity in genetic architecture. In the simplest form, Host-pathogen interactions can lead to autocorrelated variation in fitnesses. However, it remains unclear if this type of variation will generate the same kind of selective forces for modularity. These interactions provide an opportunity to study a different form of temporal variation in fitnesses and allow us to test this potentially strong form of selection.

We propose to test whether interactions between coevolving hosts and pathogens provides the conditions necessary for selection for modularity of the pathogen alleles responsible for the interaction with the host. Here we model an abstract interaction between a host and pathogen. In this paper we will compare the selective advantage of pathogens with modularity against pathogens without modularity. The working hypothesis is that antagonistic coevolutionary interactions generate substantial amounts of autocorrelated temporal variation in selection which selects modularity of the pathogen alleles responsible for the interaction with the host.

Model design: We have modeled an antagonistic interaction with two players (host and pathogen). In this system all individuals are haploid. Hosts have only one locus which is the interaction locus with multiple alleles. Pathogens have two loci. Each locus has three alleles. The fitness outcome of an interaction between a host and pathogen is modified by allele combinations at the interaction loci. We have modeled a straightforward case using a inverse matching allele model for the interaction. A match decreases the pathogen’s fitness and increases the host’s fitness. We take an abstract approach and cast this model in terms of replicator dynamics of each player in the interaction.

Model Details

Discrete or continuous?

1. Pros for discrete: easier to run iterated simulations; possible to run experiments on explicit graph structures
2. Pros for continuous: mathematical derivations cleaner

Proof of concept

Based on an individual based simulation in matlab that I coded up tonight I got a setup that we can work with while we finalize how we want this thing to work.

Glossary

Modularity Concepts

I'm quite sure that there is some overloading here; but these are the types of modularity that have come up in our discussions:

1. Modularity for reassortment (Molly)
2. Modularity for independence (Molly) (I call this 'functional decomposition' - Rob)
3. Repeated modularity: eg where a body segment occurs many times in an organism (Rob)
4. Modularity for robustness to antagonistic pleiotrophy (Molly)

Some definitions of 'modularity' drawn from the literature

Pathogen-related terms

1. Epitope : the phenotype of a pathogen that interacts with a host
   1. only need to consider a portion of the host's genome since the pathogen only targets a specialised portion of that genome.

References

Chen Y, Dokholyan N (2006) The coordinated evolution of yeast proteins is constrained by functional modularity. Trends in Genetics 22:416–419.

D’Auria G, Jim´enez N, Peris-Bondia F, Pelaz C, Latorre A, et al. (2008) Virulence factor rtx in Legionella pneumophila, evidence suggesting it is a modular multifunctional protein. BMC Genomics 9:14.

Kashtan N, Alon U (2005) Spontaneous evolution of modularity and network motifs. Proceedings of the National Academy of Sciences 102:13773– 13778.

Kirschner M, Gerhart J (1998) Evolvability. Proceedings of the National Academcy of Sciences 95:8420–8427.

Kitano H (2004) Biological robustness. Nature Reviews Genetics 5:826– 837.

Schlosser G, Wagner G (2004) Modularity in Development and Evolution. Chicago: University of Chicago Press.

Wagner G, Pavlicev M, Cheverud J (2007) The road to modularity. Nature Reviews Genetics 8:921–931.