Nramp: Deprive and conquer?

Area of Science:

• Evolutionary Biology
• Molecular Biology
• Biochemistry

Background:

• Solute carrier 11 (Slc11) family proteins evolved from bacterial MntH to eukaryotic Nramp, maintaining proton-dependent manganese import.
• Horizontal gene transfer (HGT) of Nramp into bacteria led to MntH polyphyly, complicating evolutionary understanding.
• Previous studies linked evolutionary rate shifts in Slc11 to catalytic specificity, suggesting phylogenetic analysis could reveal functional insights.

Purpose of the Study:

• To resolve the Slc11 family tree and establish a function-aware phylogenetic framework.
• To investigate the evolutionary origins and functional diversification of Slc11 proteins across bacteria, archaea, and eukaryotes.
• To explore the role of HGT in shaping Slc11/MntH evolution and function.

Main Methods:

• PHI-Blast based taxonomic profiling to analyze MntH phylogroups (A and B) and MntH C (MC) subgroups.
• Phylogenetic analysis of Slc11 proteins, including MntH and Nramp.
• Site-specific analysis of the Slc11 charge network and 3D mapping of coevolved sites.
• Alphafold modeling to predict conformational divergence.

Main Results:

• MntH B is restricted to anaerobic bacteria, while MntH A (MA) is broadly distributed; MC subgroups show niche-related spread.
• Archaea predominantly feature MA-variant MH with eukaryotic signature marks; Slc11 phylogeny places MH sister to Nramp.
• Sequential rate shifts in the Slc11 charge network and hydrophobic core correlate with evolutionary trajectory, suggesting functional adaptation.
• HGT of prototype Nramp (pN) likely benefited bacteria by enhancing proton-dependent manganese acquisition.
• Alphafold models indicate conformational divergence among MC subgroups.

Conclusions:

• Slc11 likely originated as a bacterial stress resistance mechanism for manganese acquisition under adverse conditions.
• Archaea's MH may have contributed to eukaryogenesis by acting as a manganese-sequestering defense, potentially favoring intracellular bacteria.
• The study provides a function-aware phylogenetic framework for Slc11 evolution, highlighting the impact of HGT and environmental adaptation.