Hijacking time: How Ophiocordyceps fungi could be using ant host clocks to manipulate behavior

Abstract

Ophiocordyceps fungi manipulate ant behaviour as a transmission strategy. Conspicuous changes in the daily timing of disease phenotypes suggest that Ophiocordyceps and other manipulators could be hijacking the host clock. We discuss the available data that support the notion that Ophiocordyceps fungi could be hijacking ant host clocks and consider how altering daily behavioural rhythms could benefit the fungal infection cycle. By reviewing time-course transcriptomics data for the parasite and the host, we argue that Ophiocordyceps has a light-entrainable clock that might drive daily expression of candidate manipulation genes. Moreover, ant rhythms are seemingly highly plastic and involved in behavioural division of labour, which could make them susceptible to parasite hijacking. To provisionally test whether the expression of ant behavioural plasticity and rhythmicity genes could be affected by fungal manipulation, we performed a gene co-expression network analysis on ant time-course data and linked it to available behavioural manipulation data. We found that behavioural plasticity genes reside in the same modules as those affected during fungal manipulation. These modules showed significant connectivity with rhythmic gene modules, suggesting that Ophiocordyceps could be indirectly affecting the expression of those genes as well.

Keywords: Zombie ants; behavioural plasticity; circadian plasticity; entomopathogens; infectious disease.

FIGURE 1

Gene co‐expression network (GCN) in Camponotus floridanus ant brains. (A) The annotated gene co‐expression network summarizes our overrepresentation analyses and identifies different modules of interest that are putatively important for the interplay of rhythmicity, behavioural plasticity and parasitic behavioural manipulation. The connectivity patterns between the gene modules are shown; thick edges indicate correlations ≥0.8, thinner edges indicate correlations between 0.6 and 0.8, and no edges indicate correlations <0.6. (B) The heatmap summarizes the pairwise Fisher's exact tests used to annotate the ant brain GCN. Box colours represent odds ratio, and the Benjamini–Hochberg corrected p‐values are shown together with the number of overlapping genes between module–geneset pairs in parenthesis. Non‐significant overlaps are indicated as N.S., and the total number of genes in each module or geneset is shown in parenthesis as well. (C) Daily expression pattern of all genes in each of the rhythmic and plasticity modules are shown. Each red line represents the expression of a single gene, every 2 h over a 24‐h day in forager brains. The black line represents the module's median gene expression. The x‐axis shows the time of day or Zeitgeber Time (ZT) in hours, whereas the y‐axis shows normalized gene expression as z‐scores calculated from log2‐transformed expression data. White background indicates the light phase (lights on at ZT24/ZT0), and grey background indicates the dark phase (lights turned off at ZT12). (D) The significantly overrepresented Gene Ontology (GO) terms in the behavioural plasticity/manipulation modules (Modules 6 and 9) and the correlated rhythmic modules (Modules 4 and 12). Module 12 is not depicted since it was only overrepresented in one GO term (i.e. membrane). The number in parenthesis indicates the percentage of all genes annotated with the GO term found in the module, if it was higher than 10%