Eukaryotic transposable elements as “cargo carriers”: the forging of metal resistance in the fungusPaecilomyces variotii

Abstract

29The horizontal transfer of large gene clusters by mobile elements is a key driver of prokaryotic 30 adaptation in response to environmental stresses. Eukaryotic microbes face similar 31 environmental stresses yet a parallel role for mobile elements has not yet been established. A 32 stress faced by all microorganisms is the prevalence of toxic metals in their environment. In 33 fungi, identified mechanisms for protection against metals generally rely on genes that are 34 dispersed within an organism's genome. Here we have discovered a large (~85 kb) region that 35 confers resistance to several metals in the genomes of some, but not all, strains of a fungus, 36Paecilomyces variotii. We name this region HEPHAESTUS (Hϕ) and present evidence that this 37 region is mobile within the P. variotii genome with features highly characteristic of a 38 transposable element. While large gene clusters including those for the synthesis of secondary 39 metabolites have been widely reported in fungi, these are not mobile within fungal genomes. 40 HEPHAESTUS contains the greatest complement of host-beneficial genes carried by a 41 transposable element in eukaryotes. This suggests that eukaryotic transposable elements might 42 play a role analogous to their bacterial counterparts in the horizontal transfer of large regions of 43 host-beneficial DNA. Genes within HEPHAESTUS responsible for individual metal resistances 44 include those encoding a P-type ATPase transporter, PcaA, required for cadmium and lead 45 resistance, a transporter, ZrcA, providing resistance to zinc, and a multicopper oxidase, McoA, 46 conferring resistance to copper. Additionally, a subregion of Hϕ conferring resistance to 47 arsenate was identified. The presence of a strikingly similar cluster in the genome of another 48 fungus, Penicillium fuscoglaucum, suggests that HEPHAESTUS arrived in P. variotii via horizontal 49 gene transfer.50 51 KEYWORDS 52 53 Eurotiales, gene cluster, metal homeostasis, horizontal gene transfer, transposon 54 3 INTRODUCTION 55 56Metals are used within diverse fields such as agriculture, construction, electronics and 57 pharmaceutical science. A number of these, such as cadmium, lead and arsenic, are toxic even 58 at low levels of exposure and thus environmental contamination resulting from their use is an 59 increasing concern 1 . The prevalence of toxic metals in the environment is of particular 60 relevance to fungal biology. Some fungi are able to accumulate metals to high concentrations, 61 making such fungi dangerous for human consumption 2,3 , allowing bioremediation of 62 contaminated sites 4 or concentrating valuable metals for extraction 5 . Zinc and copper play 63 essential roles in many cellular functions and are often important in fungal virulence 6 . However, 64 at high concentrations these metals can also be toxic; for example, copper-based molecules are 65 frequently used as fungicides in agriculture. 66 67 Compared to prokaryotes, our understanding of the evolutionary mechanisms through which 68 eukaryotes have ada...

The Enterprise, a massive transposon carrying Spok meiotic drive genes

“…In the first case, a hAT element is associated with the HGT of toxin genes among cereal pathogens (McDonald et al 2019). The second case comes from a recent publication which described a TE named HEPHAESTUS in the fungus Paecilomyces (Urquhart et al 2020). It carries multiple genes that provide resistance to at least five different heavy metals and shows evidence of transfer with a distantly related species of Penicillium.…”

GiantStarshipelements mobilize accessory genes in fungal genomes

“…For example, some predicted cargo suggests mobile element fitness could come at the host's expense: numerous Starships contain homologs to spore killing (Spok) genes that encode a toxin-antitoxin meiotic drive system capable of killing developing sexual progeny in Enterprise 19,34 (Figure 1B, Table S13). In contrast, many cargo genes have putatively adaptive functions that would hypothetically benefit the host in certain environments: several carry biosynthetic gene clusters (BGCs) involved in the production of secondary metabolites (e.g., Defiant and Galactica); others carry characterized virulence factors or homologs of known virulence factors (e.g., ToxA 21 , Ago1 in Argo 35 , OCH1 in Voyager and Derelict [36][37][38] ); HEPHAESTUS contains several genes characterized to contribute to heavy metal resistance 20 ; finally, FREs that are conserved across multiple Starships are part of a large metalloreductase family with several characterized members, suggesting some confer benefit to the host, for example, in the acquisition of iron in growth limiting environments or contributions to pathogen virulence [39][40][41] . While the few Starship-like regions we identified in our Basidiomycete outgroup lacked FRE homologs, they contain homologs to Fet3p and Ftr1p which form a high affinity iron permease complex in yeast 42 , suggesting a functional association convergently evolved between iron metabolism and Starships (Figure 1B).…”

“…Our work with M. phaseolina further suggests that Starship characterization will be important for understanding the emergence of virulence in pathogen populations. Starships carrying diverse accessory genes are found in fungi ranging from saprotrophs to lichens to human and plant pathogens and are further known to encode adaptive traits 20,21 , which coupled with their potential role in mediating life history trade-offs, underscores their vast potential for shaping ecological outcomes across an entire kingdom. The Starship activity that we observe in present-day fungal populations likely represents only a fraction of their historical impact, as their activity has been ongoing for millions of years.…”

“…The copyright holder for this preprint this version posted December 14, 2021. ; https://doi.org/10.1101/2021.12.13.472469 doi: bioRxiv preprint little is known about these elements, initial studies suggest they impact host fitness, that some are horizontally acquirable, and are pervasive across multiple species 16,[19][20][21][22] . Yet despite compelling preliminary evidence, the diversity, phylogenetic relationships, and contributions towards genome and pangenome evolution of large mobile elements are not well understood.…”

“…Several small cargo-carrying eukaryotic mobile elements in specific species have recently been shown to generate genome content variation by increasing the copy numbers of their accessory genes 17,18 . Larger eukaryotic mobile elements have only been identified recently, and though little is known about these elements, initial studies suggest they impact host fitness, that some are horizontally acquirable, and are pervasive across multiple species 16,[19][20][21][22] . Yet despite compelling preliminary evidence, the diversity, phylogenetic relationships, and contributions towards genome and pangenome evolution of large mobile elements are not well understood.…”