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We sought insights into the possible functions of META1 by studying its evolutionary origins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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<jats:italic>Leishmania<\/jats:italic>genome,<jats:italic>META1<\/jats:italic>sequence is under negative selection pressure against change\/substitution. Using homology modeling of<jats:italic>Leishmania<\/jats:italic>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<jats:italic>Shigella<\/jats:italic>. 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<jats:italic>Leishmania<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Overall, this work uses an evolutionary biology approach, 3D-modeling and site-directed mutagenesis to arrive at new insights into functions of<jats:italic>Leishmania<\/jats:italic>META1.<\/jats:p><\/jats:sec>","DOI":"10.1186\/1471-2148-11-334","type":"journal-article","created":{"date-parts":[[2012,2,8]],"date-time":"2012-02-08T07:53:47Z","timestamp":1328687627000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Evolutionary and functional insights into Leishmania META1: evidence for lateral gene transfer and a role for META1 in secretion"],"prefix":"10.1186","volume":"11","author":[{"given":"Vidhi","family":"Puri","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aneesh","family":"Goyal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajan","family":"Sankaranarayanan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anton J","family":"Enright","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tushar","family":"Vaidya","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2011,11,17]]},"reference":[{"key":"1964_CR1","doi-asserted-by":"crossref","first-page":"3102","DOI":"10.4049\/jimmunol.155.6.3102","volume":"155","author":"A Brittingham","year":"1995","unstructured":"Brittingham A, Morrison CJ, McMaster WR, McGwire BS, Chang KP, Mosser DM: Role of the Leishmania surface protease gp63 in complement fixation, cell adhesion, and resistance to complement-mediated lysis. 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