RESUMEN
The genetic diversity of Yersinia pestis, the etiologic agent of plague, is extremely limited because of its recent origin coupled with a slow clock rate. Here we identified 2,326 SNPs from 133 genomes of Y. pestis strains that were isolated in China and elsewhere. These SNPs define the genealogy of Y. pestis since its most recent common ancestor. All but 28 of these SNPs represented mutations that happened only once within the genealogy, and they were distributed essentially at random among individual genes. Only seven genes contained a significant excess of nonsynonymous SNP, suggesting that the fixation of SNPs mainly arises via neutral processes, such as genetic drift, rather than Darwinian selection. However, the rate of fixation varies dramatically over the genealogy: the number of SNPs accumulated by different lineages was highly variable and the genealogy contains multiple polytomies, one of which resulted in four branches near the time of the Black Death. We suggest that demographic changes can affect the speed of evolution in epidemic pathogens even in the absence of natural selection, and hypothesize that neutral SNPs are fixed rapidly during intermittent epidemics and outbreaks.
Asunto(s)
Evolución Molecular , Flujo Genético , Variación Genética , Tasa de Mutación , Yersinia pestis/genética , Secuencia de Bases , China , Genética de Población , Funciones de Verosimilitud , Modelos Genéticos , Epidemiología Molecular , Datos de Secuencia Molecular , Filogenia , Polimorfismo de Nucleótido Simple/genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: Developing a novel COVID-19 multi-epitope vaccine (CoVMEV) is essential to containing the SARS-CoV-2 pandemic. METHODS: The virus's immunodominant B and T cell epitopes from the S protein were found and joined to create the CoVMEV. Bioinformatics techniques were used to investigate the secondary and tertiary structures, as well as the physical and chemical properties of CoVMEV. RESULTS: CoVMEV exhibited high antigenicity and immunogenicity scores, together with good water solubility and stability. Toll-like receptor 2 (TLR2) and toll-like receptor4 (TLR4), which are critical in triggering immunological responses, were also strongly favoured by CoVMEV. Molecular dynamics simulation and immune stimulation studies revealed that CoVMEV effectively activated T and B lymphocytes, and increased the number of active CD8+ T cells than similar vaccines. CONCLUSION: CoVMEV holds promise as a potential vaccine candidate for COVID-19, given its robust immunogenicity, stability, antigenicity, and capacity to stimulate a strong immune response. This study presents a significant design concept for the development of peptidyl vaccines targeting SARS-CoV-2. Further investigation and clinical trials will be crucial in assessing the efficacy and safety of CoVMEV as a potential vaccine for COVID-19.