International Journal of Medical Microbiology 304 (2014) 742–748 Contents lists available at ScienceDirect International Journal of Medical Microbiology j ourna l ho me page: www.elsevier.com/locate/ijmm Gene cooption in Mycobacteria and search for virulence attributes: Comparative proteomic analyses of Mycobacterium tuberculosis, Mycobacterium indicus pranii and other mycobacteria Yadvir Singh a,1 , Sakshi Kohli a,1 , Divya Tej Sowpati b,1 , Syed Asad Rahman c , Anil K. Tyagi d , Seyed E. Hasnain a,b,∗ a Kusuma School of Biological Sciences, Indian Institute of Technology, Hauz Khas, New Delhi 110016, India b Dr Reddy’s Institute of Life Sciences, University of Hyderabad Campus, Gachibowli, Professor C.R. Rao Road, Hyderabad 500046, India c European Molecular Biology Laboratory (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton CB10 1SD, UK d Department of Biochemistry, University of Delhi South Campus, Benito Juarez Marg, New Delhi, India a r t i c l e i n f o Article history: Received 22 November 2013 Received in revised form 16 May 2014 Accepted 21 May 2014 Keywords: Tuberculosis M.tb MIP Virulence factors Gene cooption PE PGRS a b s t r a c t Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a leading infectious disease taking one human life every 15 s globally. Mycobacterium undergoes reductive evolution; the ancestors have bigger genome size and rich in metabolic pathways. Mycobacterium indicus pranii (MIP) is placed much above Mycobac- terium tuberculosis (M.tb) in evolutionary scale and is a non-pathogenic, saprophytic mycobacterium. Our in silico comparative proteomic analyses of virulence factors of M.tb and their homologs in 12 dif- ferent Mycobacterial species, including MIP, point toward gene cooption as an important mechanism in evolution of mycobacteria. We propose that adaptive changes in niche factors of non-pathogenic mycobacterium, together with novel gene acquisitions, are key players in the evolution of pathogenic- ity. Antigenic analyses between M.tb and MIP highlighted the importance of PE/PPE family in host immunomodulation, further supporting the likely potential of MIP as an effective vaccine against TB. © 2014 Elsevier GmbH. All rights reserved. Introduction The genus mycobacterium consists of more than 120 species, which can be easily categorized into strict pathogens like Mycobac- terium tuberculosis (M.tb), opportunistic pathogens like M. avium and non-pathogens like M. smegmatis. The genome size of non- pathogens is larger than that of strict pathogens suggesting that loss of genes is an integral part of ongoing evolution of slow growing mycobacterial pathogens (Ahmed et al., 2008; Brosch et al., 2002). In addition to the known reductionist evolution in mycobacterium, few families like PE/PPE, MCE have expanded down the evolution- ary course. Gene acquisition helps the bacteria to diversify and adapt in a varying environmental conditions (Juhas et al., 2009). M.tb has acquired genes specific to its survival in the host since its divergence from the common ancestor with the closest relative ∗ Corresponding author at: Kusuma School of Biological Sciences, Indian Institute of Technology, HauzKhas, New Delhi 110016, India. Tel.: +91 1126597522; fax: +91 1126597530. E-mail addresses: seyedhasnain@gmail.com, sehiitd@gmail.com (S.E. Hasnain). 1 These authors contributed equally to this work. M. kansasii (Veyrier et al., 2011) or M. canettii (Supply et al., 2013) or M. marinum which can survive in a broader environmental niche (Stinear et al., 2008). Thus, mycobacterium evolution involves both losses of genes, not critical for survival in the host, from saprophytic predecessor, and gain of few to help the pathogens establish in the host. Gene cooption involves gain of new function of a gene by dupli- cation or without duplication. Without gene duplication, genes can be coopted for some other function by change in coding sequences and gain of novel domains. On the other hand gene duplication can assist in cooption by either sub-functionalization (conservation of function partially) or neo-functionalization (gain of a new function) of the paralogous genes (True and Carroll, 2002). Gene cooption has also been used to explain the presence of virulence factors in both pathogenic and environmental Rhodococci bacteria, which belong to the same taxonomical order as M.tb (Letek et al., 2010). Mycobacterium indicus pranii (MIP), a saprophytic non- pathogenic mycobacterium, is placed in M. avium complex of mycobacteria and is evolutionary close to opportunistic pathogens of the MAC family (Ahmed et al., 2007; Saini et al., 2009). This unique placement of MIP on the mycobacterium evolutionary scale gives it the benefit of sharing more number of virulence factors http://dx.doi.org/10.1016/j.ijmm.2014.05.006 1438-4221/© 2014 Elsevier GmbH. All rights reserved.