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Council for Higher Education, Israel
Gene fusions can give rise to somatic alterations in cancers. Fusion genes have the potential to create chimeric RNAs, which can generate the phenotypic diversity of cancer cells, and could be associated with novel molecular functions related to cancer cell survival and proliferation. The expression of chimeric RNAs in cancer cells might impact diverse cancer-related functions, including loss of apoptosis and cancer cell plasticity, and promote oncogenesis. Due to their recurrence in cancers and functional association with oncogenic processes, chimeric RNAs are considered biomarkers for cancer diagnosis. Several recent studies demonstrated that chimeric RNAs could lead to the generation of new functionality for the resistance of cancer cells against drug therapy. Therefore, targeting chimeric RNAs in drug resistance cancer could be useful for developing precision medicine. So, understanding the functional impact of chimeric RNAs in cancer cells from an evolutionary perspective will be helpful to elucidate cancer evolution, which could provide a new insight to design more effective therapies for cancer patients in a personalized manner.
Sumit Mukherjee; Henry H. Heng; Milana Frenkel-Morgenstern. Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells. Cancers 2021, 13, 4328 .
AMA StyleSumit Mukherjee, Henry H. Heng, Milana Frenkel-Morgenstern. Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells. Cancers. 2021; 13 (17):4328.
Chicago/Turabian StyleSumit Mukherjee; Henry H. Heng; Milana Frenkel-Morgenstern. 2021. "Emerging Role of Chimeric RNAs in Cell Plasticity and Adaptive Evolution of Cancer Cells." Cancers 13, no. 17: 4328.
Circulating animal coronaviruses occasionally infect humans. The SARS‐CoV‐2 coronavirus is responsible for the current worldwide outbreak of COVID‐19 that has resulted in 2,112,844 deaths as of late January, 2021. We compared genetic code preferences in 496 viruses, including 34 coronaviruses, and 242 corresponding hosts, to uncover patterns that distinguish single and “promiscuous” multiple host‐infecting viruses. Based on a codon usage preference score, promiscuous viruses were shown to significantly employ non‐optimal codons, namely, codons that involve "wobble" binding to anti‐codons, as compared to single host viruses. The codon adaptation index (CAI) and the effective number of codons (ENC) were calculated for all viruses and hosts. Promiscuous viruses were less adapted hosts versus single host viruses (p‐value=4.392e‐11). All coronaviruses exploit non‐optimal codons to infect multiple hosts. We found that non‐optimal codon preferences at the beginning of viral coding sequences enhance the translational efficiency of viral proteins within the host. Finally, coronaviruses lack endogenous RNA degradation motifs to a significant degree, thereby increasing viral mRNA burden and infection load. To conclude, we found that promiscuously infecting coronaviruses prefer non‐optimal codon usage to remove degradation motifs from their RNAs and to dramatically increase their viral RNA production rates.
Gon Carmi; Alessandro Gorohovski; Sumit Mukherjee; Milana Frenkel‐Morgenstern. Non‐optimal codon usage preferences of coronaviruses determine their promiscuity for infecting multiple hosts. The FEBS Journal 2021, 1 .
AMA StyleGon Carmi, Alessandro Gorohovski, Sumit Mukherjee, Milana Frenkel‐Morgenstern. Non‐optimal codon usage preferences of coronaviruses determine their promiscuity for infecting multiple hosts. The FEBS Journal. 2021; ():1.
Chicago/Turabian StyleGon Carmi; Alessandro Gorohovski; Sumit Mukherjee; Milana Frenkel‐Morgenstern. 2021. "Non‐optimal codon usage preferences of coronaviruses determine their promiscuity for infecting multiple hosts." The FEBS Journal , no. : 1.
The recently emerged SARS-CoV-2 virus is responsible for the ongoing COVID-19 pandemic that has rapidly developed into a global public health threat. Patients severely affected with COVID-19 present distinct clinical features, including acute respiratory disorder, neutrophilia, cytokine storm, and sepsis. In addition, multiple pro-inflammatory cytokines are found in the plasma of such patients. Transcriptome sequencing of different specimens obtained from patients suffering from severe episodes of COVID-19 shows dynamics in terms of their immune responses. However, those host factors required for SARS-CoV-2 propagation and the underlying molecular mechanisms responsible for dysfunctional immune responses during COVID-19 infection remain elusive. In the present study, we analyzed the mRNA-long non-coding RNA (lncRNA) co-expression network derived from publicly available SARS-CoV-2-infected transcriptome data of human lung epithelial cell lines and bronchoalveolar lavage fluid (BALF) from COVID-19 patients. Through co-expression network analysis, we identified four differentially expressed lncRNAs strongly correlated with genes involved in various immune-related pathways crucial for cytokine signaling. Our findings suggest that the aberrant expression of these four lncRNAs can be associated with cytokine storms and anti-viral responses during severe SARS-CoV-2 infection of the lungs. Thus, the present study uncovers molecular interactions behind the cytokine storm activation potentially responsible for hyper-inflammatory responses in critical COVID-19 patients.
Sumit Mukherjee; Bodhisattwa Banerjee; David Karasik; Milana Frenkel-Morgenstern. mRNA-lncRNA Co-Expression Network Analysis Reveals the Role of lncRNAs in Immune Dysfunction during Severe SARS-CoV-2 Infection. Viruses 2021, 13, 402 .
AMA StyleSumit Mukherjee, Bodhisattwa Banerjee, David Karasik, Milana Frenkel-Morgenstern. mRNA-lncRNA Co-Expression Network Analysis Reveals the Role of lncRNAs in Immune Dysfunction during Severe SARS-CoV-2 Infection. Viruses. 2021; 13 (3):402.
Chicago/Turabian StyleSumit Mukherjee; Bodhisattwa Banerjee; David Karasik; Milana Frenkel-Morgenstern. 2021. "mRNA-lncRNA Co-Expression Network Analysis Reveals the Role of lncRNAs in Immune Dysfunction during Severe SARS-CoV-2 Infection." Viruses 13, no. 3: 402.
The recent outbreak of COVID-19 has generated an enormous amount of Big Data. To date, the COVID-19 Open Research Dataset (CORD-19), lists ∼130,000 articles from the WHO COVID-19 database, PubMed Central, medRxiv, and bioRxiv, as collected by Semantic Scholar. According to LitCovid (11 August 2020), ∼40,300 COVID19-related articles are currently listed in PubMed. It has been shown in clinical settings that the analysis of past research results and the mining of available data can provide novel opportunities for the successful application of currently approved therapeutics and their combinations for the treatment of conditions caused by a novel SARS-CoV-2 infection. As such, effective responses to the pandemic require the development of efficient applications, methods and algorithms for data navigation, text-mining, clustering, classification, analysis, and reasoning. Thus, our COVID19 Drug Repository represents a modular platform for drug data navigation and analysis, with an emphasis on COVID-19-related information currently being reported. The COVID19 Drug Repository enables users to focus on different levels of complexity, starting from general information about (FDA-) approved drugs, PubMed references, clinical trials, recipes as well as the descriptions of molecular mechanisms of drugs’ action. Our COVID19 drug repository provide a most updated world-wide collection of drugs that has been repurposed for COVID19 treatments around the world.
Dmitry Tworowski; Alessandro Gorohovski; Sumit Mukherjee; Gon Carmi; Eliad Levy; Rajesh Detroja; Sunanda Biswas Mukherjee; Milana Frenkel-Morgenstern. COVID19 Drug Repository: text-mining the literature in search of putative COVID19 therapeutics. Nucleic Acids Research 2020, 49, D1113 -D1121.
AMA StyleDmitry Tworowski, Alessandro Gorohovski, Sumit Mukherjee, Gon Carmi, Eliad Levy, Rajesh Detroja, Sunanda Biswas Mukherjee, Milana Frenkel-Morgenstern. COVID19 Drug Repository: text-mining the literature in search of putative COVID19 therapeutics. Nucleic Acids Research. 2020; 49 (D1):D1113-D1121.
Chicago/Turabian StyleDmitry Tworowski; Alessandro Gorohovski; Sumit Mukherjee; Gon Carmi; Eliad Levy; Rajesh Detroja; Sunanda Biswas Mukherjee; Milana Frenkel-Morgenstern. 2020. "COVID19 Drug Repository: text-mining the literature in search of putative COVID19 therapeutics." Nucleic Acids Research 49, no. D1: D1113-D1121.
Human Cytomegalovirus has been implicated as a probable cause for the development of hepatic cholestasis among neonates. Our study tried to ascertain the exact demographic, biochemical and immunological markers to differentially diagnose patients with HCMV associated intrahepatic and extrahepatic cholestasis and also decipher the phylogenetic variability among the viral strains infecting the two groups. A total of 110 neonates collected over a span of 2 years were selected for the study classified into four different groups based on the presence of hepatic cholestasis and active HCMV infection. Our analysis predicted that total Cholesterol, GGT, ALP and TNFα were the only significant biological markers with exact cut-off scores, capable of distinguishing between HCMV associated intrahepatic and extrahepatic cholestasis. We confirmed that in patients belonging to both of these groups, the inflammasome is activated and the extent of this activation is more or less same except for the initial activators NLRP3 and AIM2 respectively. When we performed two separate phylogenetic analyses with HCMV gM and gN gene sequences, we found that in both cases the sequences from the IHC and EHC groups formed almost separate phylogenetic clusters. Our study has shown that the HCMV clinical strains infecting at intrahepatic and extrahepatic sites are phylogenetically segregated as distinct clusters. These two separate groups show different physiological as well as immunological modulations while infecting a similar host.
Aroni Chatterjee; Sumit Mukherjee; Biswanath Basu; Debsopan Roy; Rivu Basu; Hiya Ghosh; Lopamudra Mishra; Mala Bhattacharya; Nilanjan Chakraborty. Insight into the distinctive paradigm of Human Cytomegalovirus associated intrahepatic and extrahepatic cholestasis in neonates. Scientific Reports 2020, 10, 1 -16.
AMA StyleAroni Chatterjee, Sumit Mukherjee, Biswanath Basu, Debsopan Roy, Rivu Basu, Hiya Ghosh, Lopamudra Mishra, Mala Bhattacharya, Nilanjan Chakraborty. Insight into the distinctive paradigm of Human Cytomegalovirus associated intrahepatic and extrahepatic cholestasis in neonates. Scientific Reports. 2020; 10 (1):1-16.
Chicago/Turabian StyleAroni Chatterjee; Sumit Mukherjee; Biswanath Basu; Debsopan Roy; Rivu Basu; Hiya Ghosh; Lopamudra Mishra; Mala Bhattacharya; Nilanjan Chakraborty. 2020. "Insight into the distinctive paradigm of Human Cytomegalovirus associated intrahepatic and extrahepatic cholestasis in neonates." Scientific Reports 10, no. 1: 1-16.
A new coronavirus infection, COVID-19, has recently emerged, and has caused a global pandemic along with an international public health emergency. Currently, no licensed vaccines are available for COVID-19. The identification of immunodominant epitopes for both B- and T-cells that induce protective responses in the host is crucial for effective vaccine design. Computational prediction of potential epitopes might significantly reduce the time required to screen peptide libraries as part of emergent vaccine design. In our present study, we used an extensive immunoinformatics-based approach to predict conserved immunodominant epitopes from the proteome of SARS-CoV-2. Regions from SARS-CoV-2 protein sequences were defined as immunodominant, based on the following three criteria regarding B- and T-cell epitopes: (i) they were both mapped, (ii) they predicted protective antigens, and (iii) they were completely identical to experimentally validated epitopes of SARS-CoV. Further, structural and molecular docking analyses were performed in order to understand the binding interactions of the identified immunodominant epitopes with human major histocompatibility complexes (MHC). Our study provides a set of potential immunodominant epitopes that could enable the generation of both antibody- and cell-mediated immunity. This could contribute to developing peptide vaccine-based adaptive immunotherapy against SARS-CoV-2 infections and prevent future pandemic outbreaks.
Sumit Mukherjee; Dmitry Tworowski; Rajesh Detroja; Sunanda Biswas Mukherjee; Milana Frenkel-Morgenstern. Immunoinformatics and Structural Analysis for Identification of Immunodominant Epitopes in SARS-CoV-2 as Potential Vaccine Targets. Vaccines 2020, 8, 290 .
AMA StyleSumit Mukherjee, Dmitry Tworowski, Rajesh Detroja, Sunanda Biswas Mukherjee, Milana Frenkel-Morgenstern. Immunoinformatics and Structural Analysis for Identification of Immunodominant Epitopes in SARS-CoV-2 as Potential Vaccine Targets. Vaccines. 2020; 8 (2):290.
Chicago/Turabian StyleSumit Mukherjee; Dmitry Tworowski; Rajesh Detroja; Sunanda Biswas Mukherjee; Milana Frenkel-Morgenstern. 2020. "Immunoinformatics and Structural Analysis for Identification of Immunodominant Epitopes in SARS-CoV-2 as Potential Vaccine Targets." Vaccines 8, no. 2: 290.
Congenital nephrotic syndrome (CNS) is a rare but serious condition which affects neonates and is caused by monogenic defects of glomerular structural proteins or congenital viral infections. Several reports have established a causal relationship between human cytomegalovirus (HCMV) intrauterine infection and CNS, but thorough study assessing parameters has not yet been done. This study aimed to ascertain significant demographic, biochemical, serological, inflammatory and etiological parameters with 12 months follow-up to clinically identify and monitor neonates with HCMV-associated CNS and sought to decipher the phylogenetic nature of infecting strains. Differences between four patient groups (neonates < 4 weeks old) with or without CNS and HCMV infection were compared by unpaired t testing and one-way analysis of variance (ANOVA). Linear regression was performed to assess statistical significance among individual groups. Maximum-likelihood-based phylogenetic analysis was performed with HCMV gH gene sequences to compare clinically isolated and referenced NCBI strains. This was further supported by analysis of effective number of codons (ENc), codon adaptation index (CAI) and mRNA structural variation. Patients with HCMV-associated CNS were found to have significant variations in many studied parameters compared with controls. The majority of clinical strains formed a separate phylogenetic cluster defining them as somewhat distinct from standard reference strains, which was supported by the other analyses. This study defined parameters for monitoring cases of HCMV-associated CNS, which suggest the possible existence of a selection force acting and rendering these HCMV strains able to infect selective host tissues and cause specific disease types.
Aroni Chatterjee; Sumit Mukherjee; Biswanath Basu; Debsopan Roy; Rivu Basu; Hiya Ghosh; Mala Bhattacharya; Nilanjan Chakraborty. A cross-sectional study exploring disease characteristics and phylogenetic nature of human cytomegalovirus among infected neonates with congenital nephrotic syndrome. Pediatric Nephrology 2020, 35, 1257 -1266.
AMA StyleAroni Chatterjee, Sumit Mukherjee, Biswanath Basu, Debsopan Roy, Rivu Basu, Hiya Ghosh, Mala Bhattacharya, Nilanjan Chakraborty. A cross-sectional study exploring disease characteristics and phylogenetic nature of human cytomegalovirus among infected neonates with congenital nephrotic syndrome. Pediatric Nephrology. 2020; 35 (7):1257-1266.
Chicago/Turabian StyleAroni Chatterjee; Sumit Mukherjee; Biswanath Basu; Debsopan Roy; Rivu Basu; Hiya Ghosh; Mala Bhattacharya; Nilanjan Chakraborty. 2020. "A cross-sectional study exploring disease characteristics and phylogenetic nature of human cytomegalovirus among infected neonates with congenital nephrotic syndrome." Pediatric Nephrology 35, no. 7: 1257-1266.
Summary Riboswitches are cis-regulatory non-coding genomic segments that control the expression of downstream genes by undergoing conformational change upon ligand binding. We present a comprehensive database of prokaryotic riboswitches that allows the user to search for riboswitches using multiple criteria, extract information about riboswitch location and gene/operon it regulates. RiboD provides a very useful resource that can be utilized for the better understanding of riboswitch-based gene regulation in bacteria and archaea. Availability and implementation RiboD can be freely accessed on the web at http://ribod.iiserkol.ac.in/.
Sumit Mukherjee; Sukhen Das Mandal; Nikita Gupta; Matan Drory-Retwitzer; Danny Barash; Supratim Sengupta. RiboD: a comprehensive database for prokaryotic riboswitches. Bioinformatics 2019, 35, 3541 -3543.
AMA StyleSumit Mukherjee, Sukhen Das Mandal, Nikita Gupta, Matan Drory-Retwitzer, Danny Barash, Supratim Sengupta. RiboD: a comprehensive database for prokaryotic riboswitches. Bioinformatics. 2019; 35 (18):3541-3543.
Chicago/Turabian StyleSumit Mukherjee; Sukhen Das Mandal; Nikita Gupta; Matan Drory-Retwitzer; Danny Barash; Supratim Sengupta. 2019. "RiboD: a comprehensive database for prokaryotic riboswitches." Bioinformatics 35, no. 18: 3541-3543.
Riboswitches are metabolite or ion sensing cis-regulatory elements that regulate the expression of the associated genes involved in biosynthesis or transport of the corresponding metabolite. Among the nearly 40 different classes of riboswitches discovered in bacteria so far, only the TPP riboswitch has also been found in algae, plants, and in fungi where their presence has been experimentally validated in a few instances. We analyzed all the available complete fungal and related genomes and identified TPP riboswitch-based regulation systems in 138 fungi and 15 oomycetes. We find that TPP riboswitches are most abundant in Ascomycota and Basidiomycota where they regulate TPP biosynthesis and/or transporter genes. Many of these transporter genes were found to contain conserved domains consistent with nucleoside, urea and amino acid transporter gene families. The genomic location of TPP riboswitches when correlated with the intron structure of the regulated genes enabled prediction of the precise regulation mechanism employed by each riboswitch. Our comprehensive analysis of TPP riboswitches in fungi provides insights about the phylogenomic distribution, regulatory patterns and functioning mechanisms of TPP riboswitches across diverse fungal species and provides a useful resource that will enhance the understanding of RNA-based gene regulation in eukaryotes.
Sumit Mukherjee; Matan Drory Retwitzer; Danny Barash; Supratim Sengupta. Phylogenomic and comparative analysis of the distribution and regulatory patterns of TPP riboswitches in fungi. Scientific Reports 2018, 8, 1 -13.
AMA StyleSumit Mukherjee, Matan Drory Retwitzer, Danny Barash, Supratim Sengupta. Phylogenomic and comparative analysis of the distribution and regulatory patterns of TPP riboswitches in fungi. Scientific Reports. 2018; 8 (1):1-13.
Chicago/Turabian StyleSumit Mukherjee; Matan Drory Retwitzer; Danny Barash; Supratim Sengupta. 2018. "Phylogenomic and comparative analysis of the distribution and regulatory patterns of TPP riboswitches in fungi." Scientific Reports 8, no. 1: 1-13.
Riboswitches are cis-regulatory elements that regulate the expression of genes involved in biosynthesis or transport of a ligand that binds to them. Among the nearly 40 classes of riboswitches discovered so far, three are known to regulate the concentration of biologically encoded amino acids glycine, lysine, and glutamine. While some comparative genomics studies of riboswitches focusing on their gross distribution across different bacterial taxa have been carried out recently, systematic functional annotation and analysis of lysine riboswitches and the genes they regulate are still lacking. We analyzed 2785 complete bacterial genome sequences to systematically identify 468 lysine riboswitches (not counting hits from multiple strains of the same species) and obtain a detailed phylogenomic map of gene-specific lysine riboswitch distribution across diverse prokaryotic phyla. We find that lysine riboswitches are most abundant in Firmicutes and Gammaproteobacteria where they are found upstream to both biosynthesis and/or transporter genes. They are relatively rare in all other prokaryotic phyla where if present they are primarily found upstream to operons containing many lysine biosynthesis genes. The genome-wide study of the genetic organisation of the lysine riboswitches show considerable variation both within and across different Firmicute orders. Correlating the location of a riboswitch with its genomic context and its phylogenetic relationship with other evolutionarily related riboswitch carrying species, enables identification and annotation of many lysine biosynthesis, transporter and catabolic genes. It also reveals previously unknown patterns of lysine riboswitch distribution and gene/operon regulation and allows us to draw inferences about the possible point of origin of lysine riboswitches. Additionally, evidence of horizontal transfer of riboswitches was found between Firmicutes and Actinobacteria. Our analysis provides a useful resource that will lead to a better understanding of the evolution of these regulatory elements and prove to be beneficial for exploiting riboswitches for developing targeted therapies.
Sumit Mukherjee; Danny Barash; Supratim Sengupta. Comparative genomics and phylogenomic analyses of lysine riboswitch distributions in bacteria. PLOS ONE 2017, 12, e0184314 .
AMA StyleSumit Mukherjee, Danny Barash, Supratim Sengupta. Comparative genomics and phylogenomic analyses of lysine riboswitch distributions in bacteria. PLOS ONE. 2017; 12 (9):e0184314.
Chicago/Turabian StyleSumit Mukherjee; Danny Barash; Supratim Sengupta. 2017. "Comparative genomics and phylogenomic analyses of lysine riboswitch distributions in bacteria." PLOS ONE 12, no. 9: e0184314.
Summary: Riboswitches are non-coding RNA located in the 5′ untranslated regions where they bind a target metabolite used to specify the riboswitch class and control the expression of associated genes. Accurate identification of riboswitches is the first step towards understanding their regulatory and functional roles in the cell. In this article, we describe a new web application named Riboswitch Scanner which provides an automated pipeline for pHMM-based detection of riboswitches in partial as well as complete genomic sequences rapidly, with high sensitivity and specificity. Availability and implementation: Riboswitch Scanner can be freely accessed on the web at http://service.iiserkol.ac.in/∼riboscan/. Contact:[email protected] Supplementary information:Supplementary data are available at Bioinformatics online.
Sumit Mukherjee; Supratim Sengupta. Riboswitch Scanner: an efficient pHMM-based web-server to detect riboswitches in genomic sequences. Bioinformatics 2015, 32, 776 -778.
AMA StyleSumit Mukherjee, Supratim Sengupta. Riboswitch Scanner: an efficient pHMM-based web-server to detect riboswitches in genomic sequences. Bioinformatics. 2015; 32 (5):776-778.
Chicago/Turabian StyleSumit Mukherjee; Supratim Sengupta. 2015. "Riboswitch Scanner: an efficient pHMM-based web-server to detect riboswitches in genomic sequences." Bioinformatics 32, no. 5: 776-778.
Orphan genes are protein coding genes that lack recognizable homologs in other organisms. These genes were reported to comprise a considerable fraction of coding regions in all sequenced genomes and thought to be allied with organism's lineage-specific traits. However, their evolutionary persistence and functional significance still remain elusive. Due to lack of homologs with the host genome and for their probable lineage-specific functional roles, orphan gene product of pathogenic protozoan might be considered as the possible therapeutic targets. Leishmania major is an important parasitic protozoan of the genus Leishmania that is associated with the disease cutaneous leishmaniasis. Therefore, evolutionary and functional characterization of orphan genes in this organism may help in understanding the factors prevailing pathogen evolution and parasitic adaptation. In this study, we systematically identified orphan genes of L. major and employed several in silico analyses for understanding their evolutionary and functional attributes. To trace the signatures of molecular evolution, we compared their evolutionary rate with non-orphan genes. In agreement with prior observations, here we noticed that orphan genes evolve at a higher rate as compared to non-orphan genes. Lower sequence conservation of orphan genes was previously attributed solely due to their younger gene age. However, here we observed that together with gene age, a number of genomic (like expression level, GC content, variation in codon usage) and proteomic factors (like protein length, intrinsic disorder content, hydropathicity) could independently modulate their evolutionary rate. We considered the interplay of all these factors and analyzed their relative contribution on protein evolutionary rate by regression analysis. On the functional level, we observed that orphan genes are associated with regulatory, growth factor and transport related processes. Moreover, these genes were found to be enriched with various types of interaction and trafficking motifs, implying their possible involvement in host-parasite interactions. Thus, our comprehensive analysis of L. major orphan genes provided evidence for their extensive roles in host-pathogen interactions and virulence.
Sumit Mukherjee; Arup Panda; Tapash Chandra Ghosh. Elucidating evolutionary features and functional implications of orphan genes in Leishmania major. Infection, Genetics and Evolution 2015, 32, 330 -337.
AMA StyleSumit Mukherjee, Arup Panda, Tapash Chandra Ghosh. Elucidating evolutionary features and functional implications of orphan genes in Leishmania major. Infection, Genetics and Evolution. 2015; 32 ():330-337.
Chicago/Turabian StyleSumit Mukherjee; Arup Panda; Tapash Chandra Ghosh. 2015. "Elucidating evolutionary features and functional implications of orphan genes in Leishmania major." Infection, Genetics and Evolution 32, no. : 330-337.