RESUMEN
Gene inactivation through the accumulation of truncation (or premature stop codon) mutations is a common mode of evolution in bacteria. It is frequently believed to result from reductive evolutionary processes allowing purging of superfluous traits. However, several works have demonstrated that, similar to the occurrences of inactivating nonsynonymous (i.e., amino acid replacement) mutations under positive selection pressures, truncation mutations can also be adaptive where specific traits deleterious in particular environmental conditions need to be inactivated for survival. Here, we performed a comparative analysis of genome-wide accumulation of truncation mutations in Salmonella enterica serovar Typhi and Salmonella enterica serovar Paratyphi A. Considering the known convergent evolutionary trajectories in these two serovars, we expected a strong overlap of truncated genes in S. Typhi and S. Paratyphi A, emerging through either reductive or adaptive dynamics. However, we detected a distinct set of core truncated genes encoding different overrepresented functional clusters in each serovar. In 54% and 28% truncated genes in S. Typhi and S. Paratyphi A, respectively, inactivating mutations were acquired by only different subsets of isolates, instead of all isolates analyzed for that serovar. Importantly, 62% truncated genes (P < 0.001) in S. Typhi and S. Paratyphi A were also targeted by convergent amino acid mutations in different serovars, suggesting those genes to be under selection pressures. Our findings indicate significant presence of potentially adaptive truncation mutations in conjunction with the ones emerging due to reductive evolution. Further experimental and large-scale bioinformatic studies are necessary to better explore the impact of such adaptive footprints of truncation mutations in the evolution of bacterial virulence. IMPORTANCE Detecting the adaptive mutations leading to gene inactivation or loss of function is crucial for understanding their contribution in the evolution of bacterial virulence and antibiotic resistance. Such inactivating mutations, apart from being of nonsynonymous (i.e., amino acid replacement) nature, can also be truncation mutations, abruptly trimming the length of encoded proteins. Importantly, the notion of reductive evolutionary dynamics is primarily accepted toward the accumulation of truncation mutations. However, our case study on S. Typhi and S. Paratyphi A, two human-restricted systemically invasive pathogens exerting similar clinical manifestations, indicated that a significant proportion of truncation mutations emerge from positive selection pressures. The candidate genes from our study will enable directed functional assays for deciphering the adaptive role of truncation mutations in S. Typhi and S. Paratyphi A pathogenesis. Also, our genome-level analytical approach will pave the way to understand the contribution of truncation mutations in the adaptive evolution of other bacterial pathogens.
Asunto(s)
Salmonella paratyphi A , Salmonella typhi , Aminoácidos/metabolismo , Mutación , Salmonella paratyphi A/genética , Salmonella typhi/genética , SerogrupoRESUMEN
The dire need of effective preventive measures and treatment approaches against SARS-CoV-2 virus, causing COVID-19 pandemic, calls for an in-depth understanding of its evolutionary dynamics with attention to specific geographic locations, since lockdown and social distancing to prevent the virus spread could lead to distinct localized dynamics of virus evolution within and between countries owing to different environmental and host-specific selection pressures. To decipher any correlation between SARS-CoV-2 evolution and its epidemiology in India, we studied the mutational diversity of spike glycoprotein, the key player for the attachment, fusion and entry of virus to the host cell. For this, we analyzed the sequences of 630 Indian isolates as available in GISAID database till June 07, 2020 (during the time-period before the start of Unlock 1.0 in India on and from June 08, 2020), and detected the spike protein variants to emerge from two major ancestors - Wuhan-Hu-1/2019 and its D614G variant. Average stability of the docked spike protein - host receptor (S-R) complexes for these variants correlated strongly (R2 = 0.96) with the fatality rates across Indian states. However, while more than half of the variants were found unique to India, 67% of all variants showed lower stability of S-R complex than the respective ancestral variants, indicating a possible fitness loss in recently emerged variants, despite a continuous increase in mutation rate. These results conform to the sharply declining fatality rate countrywide (>7-fold during April 11 - June 28, 2020). Altogether, while we propose the potential of S-R complex stability to track disease severity, we urge an immediate need to explore if SARS-CoV-2 is approaching mutational meltdown in India.
Asunto(s)
COVID-19/epidemiología , COVID-19/virología , Mutación , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Evolución Biológica , Humanos , India/epidemiología , CuarentenaRESUMEN
Bartonella henselae is a facultative intracellular pathogen that occurs worldwide and is responsible primarily for cat-scratch disease in young people and bacillary angiomatosis in immunocompromised patients. The principal source of genome-level diversity that contributes to B. henselae's host-adaptive features is thought to be horizontal gene transfer events. However, our analyses did not reveal the acquisition of horizontally-transferred islands in B. henselae after its divergence from other Bartonella. Rather, diversity in gene content and genome size was apparently acquired through two alternative mechanisms, including deletion and, more predominantly, duplication of genes. Interestingly, a majority of these events occurred in regions that were horizontally transferred long before B. henselae's divergence from other Bartonella species. Our study indicates the possibility that gene duplication, in response to positive selection pressures in specific clones of B. henselae, might be linked to the pathogen's adaptation to arthropod vectors, the cat reservoir, or humans as incidental host-species.
Asunto(s)
Bartonella henselae/genética , Evolución Molecular , Eliminación de Gen , Duplicación de Gen , Mosaicismo , Transferencia de Gen Horizontal , Genes Bacterianos , Genoma BacterianoRESUMEN
Shigella spp., emerging from multiple origins of Escherichia coli, poses a significant health threat as a causative agent of bacillary dysentery. While multiple serotypes of four different species have evolved via independent lineages, Shigella spp. are designated as a single pathotype, primarily because of their common mode of pathogenesis. Convergent horizontal transfer events have so far been attributed to the commonalities in the evolution of virulence across diverse lineages. However, the role of mutational convergence in such parallel evolution is not yet well understood. Here we have carried out a genome-wide analysis of Shigella strains from all four species to detect the core genes (i.e. the ones present in all analyzed strains) acquiring convergent mutations of evolutionarily recent origin. Simulation studies show non-neutral accumulation of these convergent mutations across species, suggesting their adaptive role in the evolution of Shigella virulence. S. dysenteriae strain 197, representing highly virulent type 1 (Sd1) clone, carries excessively high number of core genes with recent convergent mutations compared to other analyzed strains. We propose that this high frequency of adaptive convergence in S. dysenteriae strain 197 could be linked to recent re-emergence of the Sd1 clone and its increased resistance to antimicrobials.