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Published on: March 16, 2018
Evolutionary and functional insights into Leishmania META1: evidence for lateral gene transfer and a role for META1
Vidhi Puri1, Aneesh Goyal, Rajan Sankaranarayanan
1Centre for Cellular and Molecular Biology, Council for Scientific and Industrial Research, Uppal Road, Hyderabad - 500 007, Andhra Pradesh, India.
Background:
Leishmania META1 has for long been a candidate molecule for involvement in virulence: META1 transcript and protein are up-regulated in metacyclic Leishmania. Yet, how META1 contributes to virulence remains unclear. We sought insights into the possible functions of META1 by studying its evolutionary origins.
Results:
Using multiple criteria including sequence similarity, nucleotide composition, phylogenetic analysis and selection pressure on gene sequence, we present evidence that META1 originated in trypanosomatids as a result of a lateral gene transfer of a bacterial heat-inducible protein, HslJ. Furthermore, within the Leishmania genome, META1 sequence is under negative selection pressure against change/substitution. Using homology modeling of Leishmania META1 based on solved NMR structure of HslJ, we show that META1 and HslJ share a similar structural fold. The best hit for other proteins with similar fold is MxiM, a protein involved in the type III secretion system in Shigella. The striking structural similarity shared by META1, HslJ and MxiM suggests a possibility of shared functions. Upon structural superposition with MxiM, we have observed a putative hydrophobic cavity in META1. Mutagenesis of select hydrophobic residues in this cavity affects the secretion of the secreted acid phosphatase (SAP), indicating META1's involvement in secretory processes in Leishmania.
Conclusions:
Overall, this work uses an evolutionary biology approach, 3D-modeling and site-directed mutagenesis to arrive at new insights into functions of Leishmania META1.
Insights
Leishmania META1, a virulence candidate, likely originated from a bacterial heat-inducible protein via lateral gene transfer. Structural analysis reveals META1
Area of Science:
- Evolutionary Biology
- Molecular Parasitology
- Structural Biology
Background:
- Leishmania META1 is implicated in virulence, with elevated expression in metacyclic stages.
- The precise function of META1 in Leishmania virulence remains poorly understood.
- Investigating META1's evolutionary origins may elucidate its functional roles.
Purpose of the Study:
- To explore the evolutionary origins of Leishmania META1.
- To understand the functional implications of META1's evolutionary history.
- To investigate META1's role in Leishmania secretory processes.
Main Methods:
- Phylogenetic analysis and sequence comparison to determine META1's origin.
- Homology modeling of Leishmania META1 based on bacterial HslJ structure.
- Site-directed mutagenesis to probe META1 function in secretion.
Main Results:
- Evidence suggests Leishmania META1 arose from a bacterial heat-inducible protein (HslJ) through lateral gene transfer.
- META1 shares structural similarity with bacterial HslJ and Shigella's MxiM, hinting at conserved functions.
- Mutagenesis affecting a hydrophobic cavity in META1 impacts secreted acid phosphatase (SAP) secretion, implicating META1 in secretion.
Conclusions:
- Leishmania META1's evolutionary trajectory provides functional insights.
- META1's structural homology suggests conserved roles potentially related to secretion.
- This study links META1's evolutionary origin to its function in Leishmania secretory pathways.
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