Abstract
Genes with identical DNA sequence may show differential expression because of epigenetic marks. Where epigenetic marks respond to past conditions, they represent a form of “memory”. Despite their medical relevance, the impact of memories on the evolution of infectious diseases has rarely been considered. Here we explore the evolution of virulence in pathogens that carry memories of the sex of their previous host. We show that this form of memory provides information about the sex of present and future hosts when the sexes differ in their pathogen’s transmission pattern. Memories of past hosts enable the evolution of greater virulence in infections originating from one sex and infections transmitted across sexes. Thus, our results account for patterns of virulence that have, to date, defied medical explanation. In particular, it has been observed that girls infected by boys (or boys infected by girls) are more likely to die from measles, chickenpox and polio than girls infected by girls (or boys infected by boys). We also evaluate epigenetic therapies that tamper with the memories of infecting pathogens. More broadly, our findings imply that pathogens can be selected to carry memories of past environments other than sex. This identifies new directions in personalised medicine.
Highlights
Genes with identical DNA sequence may show differential expression because of epigenetic marks
Some of these epigenetic marks are inherited across multiple generations of the pathogen, e.g., marks carried by the EBV virus, Salmonella enterica, Candida albicans and Plasmodium falciparum[1,3,11,18]
We model transmission using a law of mass-action with rate constant βi←j, where i in this context refers to the sex of the susceptible host and j refers to the sex of the infective host
Summary
Genes with identical DNA sequence may show differential expression because of epigenetic marks. The oversight is not justified from an empirical perspective: there is abundant evidence of epigenetic marks established through exposure to environmental conditions that regulate the expression of genes underpinning virulence or transmission[1,3,10,11,12,13,14,15,16,17,18] Some of these epigenetic marks are inherited across multiple generations of the pathogen, e.g., marks carried by the EBV virus, Salmonella enterica, Candida albicans and Plasmodium falciparum[1,3,11,18]. If genes in gametic cells are able to acquire information on the sex of their current carrier and pass it on to genes in the carrier (imprinted genes) it does not seem too far fetched to consider genes in pathogens that are able to acquire information on the sex of their current host and pass it on to pathogenic genes in the host (in particular when it has been shown that pathogens can acquire information on their current environment and maintain it through division[1,3,11,18])
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