A two-speed genome architecture underlies the evolution of host manipulation in zombie-ant fungi
Parasitic manipulation of host behavior represents an extreme outcome of host-parasite coevolution, yet the genomic mechanisms underlying such precise and reproducible phenotypic control remain poorly understood. Species of the fungal genus Ophiocordyceps induce stereotyped behavioral changes in ant hosts, leading to the well-known "zombie-ant" syndrome, providing an exceptional system for investigating the genomic basis of behavioral manipulation. As members of the filamentous ascomycetes, Ophiocordyceps species may also share a genomic feature common in many Pezizomycotina: a compartmentalized "two-speed" architecture characterized by gene-dense, GC-equilibrated regions interspersed with repeat-rich, AT-rich compartments. While AT-rich regions are known to facilitate rapid adaptation in plant pathogenic fungi, their role in animal-infecting fungi remains largely unexplored. Here, we integrate genome-wide analyses of nucleotide composition, gene distribution, and evolutionary signatures to examine the relationship between AT-rich genomic compartments and host manipulation in Ophiocordyceps. We show that the genome is strongly partitioned into GC-equilibrated and AT-rich regions, consistent with a two-speed evolutionary architecture. Although AT-rich regions comprise a substantial fraction of the genome, only a small proportion of genes are located within these compartments. Notably, genes residing in AT-rich regions exhibit distinct evolutionary patterns and functional enrichments compared with those in GC-rich regions, suggesting accelerated evolution and lineage-specific innovation. Together, our results implicate AT-rich genomic compartments as evolutionary hotspots that may facilitate the emergence and diversification of genes underlying fungal manipulation of host behavior.