Host-parasite co-evolution and genetic variation at the major histocompatibility complex in the Trinidadian guppy (poecilia reticulata)

McMullan, Mark

Abstract

The Major Histocompatibility Complex (MHC) is a region of the vertebrate genome believed to be responsible for an individual's ability to detect and recognise invading parasites. The MHC molecule has been shown to bind to short fragments of parasite and present these to the adaptive immune system. Theory developed to describe the maintenance of polymorphism within the MHC has focussed on the principle that different MHC alleles recognise different groups of parasites and that parasite diversity maintains diversity in the MHC (i.e. Red Queen dynamics). Nevertheless, after 50 years of research, the precise mechanism for the maintenance of extraordinary levels of polymorphism in the MHC remains yet to be resolved.

In the present thesis, I use guppies (Poecilia reticulata) as a model to investigate the role of parasites in the maintenance of polymorphism in the MHC. In a study of spatial variation of both MHC and microsatellite variation, I find evidence to suggest that upstream populations of guppies have small population sizes and reduced gene flow into the population. However, these populations of guppies maintain similar levels of MHC polymorphism to that of larger populations of guppies further downstream. The maintenance of MHC in small upstream populations provides evidence for selection for the maintenance of MHC polymorphism despite the effect of random genetic drift. This finding is particularly interesting given that I show that this small upstream population has a significantly reduced parasite fauna. These data therefore provide evidence for other sources of selection on the MHC such as sexual selection or Associative Balancing Complex (ABC) evolution.

Balancing selection maintains polymorphism above that expected under a neutral model of evolution. However, balancing selection is a general term that encompasses several distinct mechanisms, including negative frequency dependent selection (rare allele advantage), overdominance (heterozygote advantage) and selection that favours distinct alleles in different times and/or places (fluctuating selection). I use a temporal dataset of MHC and microsatellite variation to distinguish between these different models of balancing selection. In particular, I evaluate the ability of the different models of balancing selection to explain the empirical data of two guppy populations sampled in 2001 and 2007.1 conclude that the relatively low level of spatial genetic divergence of the MHC in 2001 is most consistent with the overdominance and negative frequency dependent selection models of balancing selection. By contrast, the data in 2007 suggest that MHC is subject to fluctuating selection, showing a higher level of spatial genetic differentiation than the microsatellites. Overtime, the MHC appears to change more rapidly than neutral microsatellite loci. Using a verbal model, I argue that this pattern of temporal genetic divergence and the rapid turnover of MHC alleles is consistent with all types of balancing selection. Balancing selection increases the effective migration rate, resulting in a rapid differentiation of the MHC gene pool over generations. Such allelic turnover can however only be realised in a metapopulation with a large gene pool of MHC alleles. Both these conditions (i.e. a source-sink metapopulation with circa 85 MHC alleles) have recently been demonstrated for guppy populations in the Caroni Drainage in Trinidad by different authors. Importantly, these findings demonstrate that in an open metapopulation, the impact of migration can differ dramatically between neutral genes and genes under balancing selection.

Using a simulation model, I further explore whether the combination of balancing selection (in particular, overdominance) and gene flow in a metapopulation system can explain the large observed spatio-temporal differentiation of the MHC. Traditionally, authors have interpreted large temporal fluctuations in MHC allele frequencies as evidence for a coevolutionary arms race between host immune genes and parasite virulence genes (i.e. Red Queen dynamics). In this theoretical chapter, I explore whether such data can also be explained by simple overdominant selection in combination with migration from a source population with many distinct MHC alleles. I find that the commonly held assumption that balancing selection homogenises gene frequencies and reduces the level of genetic differentiation (G'sr) is not always correct, and it depends on the interaction between evolutionary forces and population demography. Furthermore, I demonstrate that balancing selection (overdominance) can explain the rapid turnover in MHC alleles, and that this observation should not be taken as evidence of Red Queen dynamics through host-parasite co-evolution.

Altogether, this thesis highlights two main considerations that should be made in future studies of the MHC. Firstly, other sources of balancing selection should be considered in addition to parasite selection, particularly where no causal relationship between parasites and MHC alleles has been identified. Secondly, population demography can have a different impact on the population genetics of the MHC compared to that of neutral loci. The effect of a higher effective migration rate on MHC alleles is all too often interpreted as evidence for changes in the direction of parasite-mediated selection (i.e. Red Queen dynamics). However, theoretically, other forms of balancing selection, including overdominance, negative frequency dependent selection, fluctuating selection and ABC evolution, can also drive the temporal dynamics of the MHC.

Citation

McMullan, M. (2010). Host-parasite co-evolution and genetic variation at the major histocompatibility complex in the Trinidadian guppy (poecilia reticulata). (Thesis). University of Hull. Retrieved from https://hull-repository.worktribe.com/output/4213078

• Thesis Type: Thesis
• Deposit Date: Sep 25, 2012
• Publicly Available Date: Feb 22, 2023
• Keywords: Biological sciences
• Public URL: https://hull-repository.worktribe.com/output/4213078
• Additional Information: Department of Biological Sciences, The University of Hull
• Award Date: Aug 1, 2010