Thus, the mycobacterial rhomboid paralogs may be “”outparalogs”" (i.e.

they could have resulted from duplication(s) preceding a speciation event [47]), while the RG7112 orthologs could have originated from a single ancestral gene in the last common ancestor [47]). The Neighbor-Joining and Minimum Evolution phylogenetic trees were compared and gave almost comparable selleck inhibitor results. Figure 3 Mycobacterial rhomboids have different evolutionary history. A: Mycobacterial rhomboids clustered into two distinct clades (boxed blue and red). The Rv0110 mycobacterial orthologs (boxed blue) clustered with eukaryotic active rhomboids (unboxed). The Rv1337 mycobacterial orthologs (boxed red) appeared unique. Mycobacterial rhomboids could have been acquired at the same time, and the orthologs of Rv0110 were eventually lost in the MAC species and M. leprae. Mouse-protein farnesyl transferase, FT, [GenBank: AAI38303] was the outgroup. B: MAB0026 of M. abscessus (underlined blue) is conspicuously distant from its mycobacterial orthologs (boxed blue). The Rv0110 (rhomboid protease 1) mycobacterial orthologs

(boxed blue) clustered with eukaryotic secretase and PARL rhomboids with a high Bootstrap value (85%, figure 3A). When grouped with eukaryotic iRhoms, the Bootstrap value for this clade increased to 90%, with iRhoms forming a distinct clade (not shown). The Rv0110 mycobacterial orthologs may represent prokaryotic rhomboids with GSK3235025 clinical trial similar lineage or progenitor for eukaryotic active rhomboids. This was previously noted by Koonin et al [19], who hinted on a subfamily of eukaryotic rhomboids that clustered with rhomboids of Gram positive bacteria.

Indeed, the Rv0110 mycobacterial orthologs contained extra eukaryotic motifs and have topologies similar to that of rho-1 of drosophila. Koonin et al [19] alluded that rhomboids could have emerged in a bacterial lineage and were eventually widely disseminated (to other life kingdoms) by horizontal transfer [19]. Conversely, the Rv1337 mycobacterial orthologs (boxed red) formed a distinct clade, different from Rv0110 mycabacterial orthologs. These rhomboids appeared evolutionary stable and did not cluster with eukaryotic rhomboids. MAB_0026 of M. PtdIns(3,4)P2 abscess which had low homology with Rv0110 also appeared distant and clustered poorly with mycobacterial orthologs, in contrast with its paralog MAB_1481 (figure 3A). Since orthologs have an ancestral gene in the last common ancestor [47], MAB_0026 could be a “”pseudoortholog”" (i.e. it is a distant paralog that appears orthologous due to differential, lineage-specific gene loss [47]). In phylogenetic analysis of mycobacterial rhomboids orthologous to Rv0110, MAB_0026 was also distant from rhomboids of other actinobacteria (figure 3B). Since M. abscessus is one of the earliest species to diverge of all mycobacterial species [39], the low homology could reflect evolutionary distance or stability of this rhomboid.