Nephromyces represents a diverse and novel lineage of the Apicomplexa that has retained apicoplasts

Abstract

A most interesting exception within the parasitic Apicomplexa is Nephromyces, an extracellular, probably mutualistic, endosymbiont found living inside molgulid ascidian tunicates (i.e., sea squirts). Even though Nephromyces is now known to be an apicomplexan, many other questions about its nature remain unanswered. To gain further insights into the biology and evolutionary history of this unusual apicomplexan, we aimed to (1) find the precise phylogenetic position of Nephromyces within the Apicomplexa, (2) search for the apicoplast genome of Nephromyces, and (3) infer the major metabolic pathways in the apicoplast of Nephromyces. To do this, we sequenced a metagenome and a metatranscriptome from the molgulid renal sac, the specialized habitat where Nephromyces thrives. Our phylogenetic analyses of conserved nucleus-encoded genes robustly suggest that Nephromyces is a novel lineage sister to the Hematozoa, which comprises both the Haemosporidia (e.g., Plasmodium) and the Piroplasmida (e.g., Babesia and Theileria). Furthermore, a survey of the renal sac metagenome revealed 13 small contigs that closely resemble the genomes of the non-photosynthetic reduced plastids, or apicoplasts, of other apicomplexans. We show that these apicoplast genomes correspond to a diverse set of most closely related but genetically divergent Nephromyces lineages that co-inhabit a single tunicate host. In addition, the apicoplast of Nephromyces appears to have retained all biosynthetic pathways inferred to have been ancestral to parasitic apicomplexans. Our results shed light on the evolutionary history of the only probably mutualistic apicomplexan known, Nephromyces, and provide context for a better understanding of its life style and intricate symbiosis.

Real-time dynamics of Plasmodium NDC80 reveals unusual modes of chromosome segregation during parasite proliferation

“…To increase the sensitivity for detecting highly divergent members of the NDC80 complex (NDC80, NUF2, SPC25, SPC24) in apicomplexan parasites, we constructed a large sequence database of (new) genomes and (meta)transcriptomes (see for sources). This database consisted of 43 Apicomplexa and 8 Apicomplexa-affiliated lineages, including newly sequenced gregarines and ‘Apicomonada’ ( Janouškovec et al, 2019 ; Janouškovec et al, 2015 ; Mathur et al, 2019 ), and the non-parasitic apicomplexan Nephromyces ( Muñoz-Gómez et al, 2019 ). A set of 13 eukaryotes representative of a wider range of the eukaryotic tree of life were added, for which the NDC80 complex presence/absence pattern was studied previously ( van Hooff et al, 2017 ) For transcriptomes for which no gene predictions were available, ORFs were predicted using TransDecoder (Long Orfs algorithm: ).…”

Codependence in the Nephromyces species swarm depends on heterospecific bacterial endosymbionts

“…This number is similar to some of the most gene-rich apicomplexans, such as Toxoplasma gondii, which also encodes 8,000 genes . This is interesting given the phylogenetic placement of Nephromyces in the Hematozoa (19). Hematozoa, which contains the plasmodiidae and piroplasmida lineages, have some of the smallest genomes with the least number of genes of any sequenced apicomplexans.…”

“…Nephromyces is also unusual because it lives the majority of its life extracellularly (18). Whereas some early-diverging gregarines are primarily extracellular, the Nephromycidae resolves as sister to the Hematozoans, a clade of obligate intracellular blood parasites (19). While it remains unknown if Nephromyces is capable of forming direct connections to tunicate host cells, there is no microscopic support for direct cell-to-cell connections.…”

Metabolic Contributions of an Alphaproteobacterial Endosymbiont in the Apicomplexan Cardiosporidium cionae

“…However, what defines the boundaries along this continuum of symbiotic association is still a topic of much debate (Ewald, 1987;Leung and Poulin, 2008;Johnson and Oelmüller, 2009). Phylogenetic analysis indicates Nephromyces is sister to the hematozoan clade, and closely related to highly virulent genera such as Plasmodium, Theiliera, and Babesia (Muñoz-Gómez et al, 2019a). Thus far, apicomplexan species with variable life strategies have been found in early branching groups, such as the Gregarina and Corallicods.…”

“…Nephromyces also houses three separate lineages of bacterial endosymbionts (Paight et al, 2020). Though endosymbiotic associations are commonly found in other protists such as ciliates, diatoms, and amoebas, bacterial endosymbiosis in Apicomplexa is unique to this lineage (Nowack and Melkonian, 2010), which only includes Cardiosporidium and Nephromyces (Muñoz-Gómez et al, 2019a).…”