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This study highlights the significant role of the genetic repertoire of a microorganism in the similarity between Novosphingobium strains. The results suggest that the phylogenetic relationships were mostly influenced by metabolic trait enrichment, which is possibly governed by the microenvironment of each microbe’s respective niche. Using core genome analysis, the enrichment of a certain set of genes specific to a particular habitat was determined, which provided insights on the influence of habitat on the distribution of metabolic traits for Novosphingobium strains. We also identified habitat-specific protein hubs, which suggested delineation of Novosphingobium strains based on their habitat. Examining the available genomes of ecologically diverse bacterial species and analyzing the habitat-specific genes are useful for understanding the distribution and evolution of functional and phylogenetic diversity in the genus Novosphingobium.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has resulted in 92 million cases in a span of 1 year. The study focuses on understanding population-specific variations attributing its high rate of infections in specific geographical regions particularly in the United States. Rigorous phylogenomic network analysis of complete SARS-CoV-2 genomes (245) inferred five central clades named a (ancestral), b, c, d, and e (subtypes e1 and e2). Clade d and subclade e2 were found exclusively comprised of U.S. strains. Clades were distinguished by 10 co-mutational combinations in Nsp3, ORF8, Nsp13, S, Nsp12, Nsp2, and Nsp6. Our analysis revealed that only 67.46% of single nucleotide polymorphism (SNP) mutations were at the amino acid level. T1103P mutation in Nsp3 was predicted to increase protein stability in 238 strains except for 6 strains which were marked as ancestral type, whereas co-mutation (P409L and Y446C) in Nsp13 were found in 64 genomes from the United States highlighting its 100% co-occurrence. Docking highlighted mutation (D614G) caused reduction in binding of spike proteins with angiotensin-converting enzyme 2 (ACE2), but it also showed better interaction with the TMPRSS2 receptor contributing to high transmissibility among U.S. strains. We also found host proteins, MYO5A, MYO5B, and MYO5C, that had maximum interaction with viral proteins (nucleocapsid [N], spike [S], and membrane [M] proteins). Thus, blocking the internalization pathway by inhibiting MYO5 proteins which could be an effective target for coronavirus disease 2019 (COVID-19) treatment. The functional annotations of the host-pathogen interaction (HPI) network were found to be closely associated with hypoxia and thrombotic conditions, confirming the vulnerability and severity of infection. We also screened CpG islands in Nsp1 and N conferring the ability of SARS-CoV-2 to enter and trigger zinc antiviral protein (ZAP) activity inside the host cell. IMPORTANCE In the current study, we presented a global view of mutational pattern observed in SARS-CoV-2 virus transmission. This provided a who-infect-whom geographical model since the early pandemic. This is hitherto the most comprehensive comparative genomics analysis of full-length genomes for co-mutations at different geographical regions especially in U.S. strains. Compositional structural biology results suggested that mutations have a balance of opposing forces affecting pathogenicity suggesting that only a few mutations are effective at the translation level. Novel HPI analysis and CpG predictions elucidate the proof of concept of hypoxia and thrombotic conditions in several patients. Thus, the current study focuses the understanding of population-specific variations attributing a high rate of SARS-CoV-2 infections in specific geographical regions which may eventually be vital for the most severely affected countries and regions for sharp development of custom-made vindication strategies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive single stranded RNA virus that causes a highly contagious Corona Virus Disease (COVID19). Entry of SARS-CoV-2 in human cells depends on binding of the viral spike (S) proteins to cellular receptor Angiotensin-converting enzyme 2 (ACE2) and on S protein priming by host cell serine protease TMPRSS2. Recently COVID19 has been declared pandemic by World Health Organization yet high differences in disease outcomes across countries have been seen. We provide evidences based on analyses of existing public datasets and by using various insilico approaches to explain some of these as factors that may explain population level differences. One of the key factors might be entry of virus in host cells due to differential interaction of viral proteins with host cell proteins due to different genetic backgrounds. Based on our findings, we conclude that higher expression of ACE2 facilitated by natural variations, acting as Expression quantitative trait loci (eQTLs) and with different frequencies in different populations, results in ACE2 homo-dimerization which is disadvantageous for TMPRSS2 mediated cleavage of ACE2 and becomes more difficult in presence of broad neutral amino acid transporter, B0AT1 (coded by SLC6A19), that usually does not express in Lungs. We also propose that the monomeric ACE2 has higher preferential binding with SARS-CoV-2 S-Protein vis-a-vis its dimerized counterpart. Further, eQTLs in TMPRSS2 and natural structural variations in the gene may also result in differential outcomes towards priming of viral S-protein, a critical step for entry of Virus in host cells. In addition, we suggest some other potential key host genes like ADAM17, RPS6, HNRNPA1, SUMO1, NACA,

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