Diversity and Evolution of Sensor Histidine Kinases in Eukaryotes

Abstract

Histidine kinases (HKs) are primary sensor proteins that act in cell signaling pathways generically referred to as "two-component systems" (TCSs). TCSs are among the most widely distributed transduction systems used by both prokaryotic and eukaryotic organisms to detect and respond to a broad range of environmental cues. The structure and distribution of HK proteins are now well documented in prokaryotes, but information is still fragmentary for eukaryotes. Here, we have taken advantage of recent genomic resources to explore the structural diversity and the phylogenetic distribution of HKs in the prominent eukaryotic supergroups. Searches of the genomes of 67 eukaryotic species spread evenly throughout the phylogenetic tree of life identified 748 predicted HK proteins. Independent phylogenetic analyses of predicted HK proteins were carried out for each of the major eukaryotic supergroups. This allowed most of the compiled sequences to be categorized into previously described HK groups. Beyond the phylogenetic analysis of eukaryotic HKs, this study revealed some interesting findings: 1) characterization of some previously undescribed eukaryotic HK groups with predicted functions putatively related to physiological traits; 2) discovery of HK groups that were previously believed to be restricted to a single kingdom in additional supergroups, and 3) indications that some evolutionary paths have led to the appearance, transfer, duplication, and loss of HK genes in some phylogenetic lineages. This study provides an unprecedented overview of the structure and distribution of HKs in the Eukaryota and represents a first step toward deciphering the evolution of TCS signaling in living organisms.

Fig. 1.

—Domain organization and TCSs signaling. The canonical structure of HKs is composed of: 1) a highly variable N-terminal sequence that determines which stimulus is perceived by the HK (sensing-D); 2) and both histidine kinase A (H(X)) (including a phosphorylatable histidine residue in the H-box and an X-box) and histidine kinase-like ATPase catalytic (including four distinct boxes: the N-, G1-, F-, and G2-boxes) subdomains. In prokaryotes, TCSs usually consist of a two-step phosphorelay between an HK and an RR. Perception of a stimulus induces autophosphorylation of the HK which thus acts as a primary sensor, and the phosphate is then transferred to an RR which acts as a transcription factor to directly regulate a series of genes required for an adapted response. Most eukaryotic HKs harbor an additional C-terminal receiver domain (REC) characterized by the presence of a three amino acid signature (DDK). Thus, eukaryotic HKs are generally called hybrid HKs (HHKs). In eukaryotes, TCSs are composed of additional modules, such as the Hpt domain and the signaling routes that mediate the perception of stimuli correspond to a multistep phosphorelay between three families of proteins (HHK, Hpt, and RR). In most eukaryotic TCSs, the RR either acts directly as a transcription factor or governs downstream elements (MAPK cascades, the cAMP pathway, or Raf-like kinases). Note that in a few HKs, the Hpt domain is fused to the REC domain.

Fig. 2.

—Phylogeny estimation of HK predicted protein sequences in Archaeplastida. A representative structure is provided for each defined HK group. Athal, Arabidopsis thaliana; Atric, Amborella trichopoda; Cmero, Cyanidioschyzon merolae; Cpara, Cyanophora paradoxa; Ehuxl, Emiliania huxleyi; Gthet, Guillardia theta; Knite, Klebsormidium nitens; Mpusi, Micromonas pusilla; Osati, Oryza sativa; Ppate, Physcomitrella patens; Ptaed, Pinus taeda; Smoel, Selaginella moellendorffii; Vcart, Volvox carteri.

Fig. 3.

—Phylogeny estimation of HK predicted protein sequences in Opisthokonta. A representative structure is provided for each defined HK group. Afumi, Aspergillus fumigatus; Aolig, Arthrobotrys oligospora; Bcine, Botrytis cinerea; Calbi, Candida albicans; Cangu, Catenaria anguillulae; Ccoro, Conidiobolus coronatus; Cneof, Cryptococcus neoformans; Cowcz, Capsaspora owczarzaki; Fvert, Fusarium verticillioides; Gprol, Gonapodya prolifera; Mbrev, Monosiga brevicollis; Melon, Mortierella elongata; Pgram, Puccinia graminis; Rallo, Rozella allomycis; Rbrev, Ramicandelaber brevisporus; Rirre, Rhizophagus irregularis; Splum, Syncephalis plumigaleata; Tdefo, Taphrina deformans; Tmela, Tuber melanosporum; Uflor, Usnea florida; Umayd, Ustilago maydis; Urama, Umbelopsis ramanniana; Xheve, Xylona heveae.

Fig. 4.

—Phylogeny estimation of HK predicted protein sequences in Amoebozoa. A representative structure is provided for each defined HK group. Acast, Acanthamoeba castellanii; Ddisc, Dictyostelium discoideum; Ppall, Polysphondylium pallidum; Ppoly, Physarum polycephalum.

Fig. 5.

—Phylogeny estimation of HK predicted protein sequences in Apusozoa. The structure of each HK is provided. Ttrah, Thecamonas trahens.

Fig. 6.

—Phylogeny estimation of HK predicted protein sequences in Excavata. A representative structure is provided for each defined HK group. Ngrub, Naegleria gruberi; Tvagi, Trichomonas vaginalis.

Fig. 7.

—Phylogeny estimation of HK predicted protein sequences in SAR. A representative structure is provided for each defined HK group. Aanop, Aureococcus anophagefferens; Alaib, Albugo laibachii; Esili, Ectocarpus siliculosus; Fsola, Fistulifera solaris; Pbras, Plasmodiophora brassicae; Pmar, Perkinsus marinus; Tterm, Tetrahymena termophila; Vbras, Vitrella brassicaformis.

Fig. 8.

—Occurrence of prominent HK groups in eukaryotic clades. For each eukaryotic clade, the presence of main HK groups is indicated with a pink box. The total number of predicted HK sequences is indicated in the right column.