Nramp: Deprive and conquer?

Abstract

Solute carriers 11 (Slc11) evolved from bacterial permease (MntH) to eukaryotic antibacterial defense (Nramp) while continuously mediating proton (H+)-dependent manganese (Mn2+) import. Also, Nramp horizontal gene transfer (HGT) toward bacteria led to mntH polyphyly. Prior demonstration that evolutionary rate-shifts distinguishing Slc11 from outgroup carriers dictate catalytic specificity suggested that resolving Slc11 family tree may provide a function-aware phylogenetic framework. Hence, MntH C (MC) subgroups resulted from HGTs of prototype Nramp (pNs) parologs while archetype Nramp (aNs) correlated with phagocytosis. PHI-Blast based taxonomic profiling confirmed MntH B phylogroup is confined to anaerobic bacteria vs. MntH A (MA)’s broad distribution; suggested niche-related spread of MC subgroups; established that MA-variant MH, which carries ‘eukaryotic signature’ marks, predominates in archaea. Slc11 phylogeny shows MH is sister to Nramp. Site-specific analysis of Slc11 charge network known to interact with the protonmotive force demonstrates sequential rate-shifts that recapitulate Slc11 evolution. 3D mapping of similarly coevolved sites across Slc11 hydrophobic core revealed successive targeting of discrete areas. The data imply that pN HGT could advantage recipient bacteria for H+-dependent Mn2+ acquisition and Alphafold 3D models suggest conformational divergence among MC subgroups. It is proposed that Slc11 originated as a bacterial stress resistance function allowing Mn2+-dependent persistence in conditions adverse for growth, and that archaeal MH could contribute to eukaryogenesis as a Mn2+ sequestering defense perhaps favoring intracellular growth-competent bacteria.

Emergence of Slc11 clade MCbgut: a parsimonious hypothesis for the dawn of Lactobacillales in the gut of early vertebrates

“…Prior work suggested that reevaluating the phylogenetic structure of MCb clade may delineate a putative precursor lineage (MCb ie ) from LB’s MCbs (MCb gut ): NCBI sequence wp_092092601.1 from the Carnobacteriaceae Pisciglobus halotolerans (Uniprot ID: A0A1I3CNB9), representing a cluster of sequences (seqs>70% aa id), demonstrated both MCb most basal branching node and relatively little specific divergence compared to the rest of MCb clade [7]. Detailing the phylogenetic relationships of A0A1I3CNB9 clade, i.e., MCb ie , amid eukaryotic prototype Nramps and other bacterial MntH C clades (Figure 1B) confirmed both its basal position relative to the rest of MCb homologs, i.e., MCb gut , and the relative sequence conservation of its members.…”

“…The 3D modeling properties of MCb gut templates differ from other MntH C clades, apparently due to intrinsic carrier plasticity and the presence of flexible loops [6, 7]. Based on the candidate MCb synapomorphy (Figure 3BC) one could expect that AF2/CF models of native MCb ie carriers would resemble known MCb gut structures either modeled or solved.…”

“…First, several bacterial orders enriched in MCa + spp. (e.g., Cyanobacteria, Pseudomonadales (gamma proteobacteria, GPB), Burkholderiales (BPB), Rhodobacterales, Sphingomonadales, Hyphomicrobiales (Rhizobiales, APB) [7] might have formed Precambrian subaerial microbial mats that could include Bacillus spp. [32], [33].…”

“…MntH synapomorphies demonstrate successive sets of coevolutionary rate-shifts that progressively edified an extended ‘H + -network’ interacting with the pmf, from anaerobic bacteria (MntH B, before aerobiosis) to aerobic bacteria (MntH A) and to hyperthermophile TACK and Asgard Archaea (MntH H). This latter evolutionary intermediate likely shared a common ancestor with the first eukaryotic representative of the Slc11 family (Nramp precursor, Figure 1A, [7].…”

Identification of a divalent metal transporter required for cellular iron metabolism in malaria parasites

“…All DMT1 subtype classifications (pN-I, pN-II, aN-I, aN-II) were previously assigned 39 . Prokaryotic MntH (MA) transporters were used as the outgroup.…”