02401nas a2200229 4500000000100000008004100001260001200042653000800054653001600062653002900078653003000107653003100137653000900168100001400177700001300191700001300204700001000217245013800227300001100365520178100376022001402157 2020 d c06/202010aCAI10aCodon usage10aCompositional constrains10aGC biased gene conversion10aMycobacterium lepromatosis10aRSCU1 aKhandia R1 aMunjal A1 aShende K1 aDas J00aMycobacterium lepromatosis genome exhibits unusually high CpG dinucleotide content and selection is key force in shaping codon usage. a1043993 a

Mycobacterium lepromatosis was identified as a causative agent for leprosy in the year 2008 in the United States and later more cases were identified in Canada, Singapore, Brazil, and Myanmar. It is known to cause diffuse lepromatosis leprosy among humans. Since it is invasive, the mortality rates are higher in comparison to the M. leprae. At genomic level, there exists 90.9% similarity between M. lepromatosis and M. leprae. Codon usage analysis based on analyses of 228 coding sequences (CDSs) of M. lepromatosis, revealed that the genome is GC rich. Among the total 16 dinucleotides, CpG dinucleotide possesses the highest dinucleotide frequency in M. lepromatosis, that is strikingly an unobvious observation since higher CpG is associated with higher proinflammatory cytokine production and NF-κB activation that eventually leads to high pathogenicity. To evade immune response, CpG content is generally less in pathogens. The unusually high CpG content can be explained by the fact that the nucleotide composition of M. lepromatosis is CG rich. Various forces interplay to shape codon usage pattern of any organism including selection; mutation, nucleotide composition as well as GC biased gene conversion. To understand the interplay between various forces; neutrality, parity, Nc-GC3 (Effective number of codons-GC content at 3rd position of the codon), aromaticity (AROMO) and the general average hydropathicity score (GRAVY) analyses have been carried out. The analyses revealed that selection force is the major contributory force. Along with the selection; mutation, nucleotide composition as well as GC biased gene conversion also play role in shaping codon usage bias in M. lepromatosis. This is the first report on the codon usage in M. lepromatosis.

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