India has become the third worst-hit nation by the COVID-19 pandemic caused by the SARS-CoV-2 virus. Here, we investigated the molecular, phylogenomic, and evolutionary dynamics of SARS-CoV-2 in western India, the most affected region of the country. A total of 90 genomes were sequenced. Four nucleotide variants, namely C241T, C3037T, C14408T (Pro4715Leu), and A23403G (Asp614Gly), located at 5'UTR, Orf1a, Orf1b, and Spike protein regions of the genome, respectively, were predominant and ubiquitous (90%). Phylogenetic analysis of the genomes revealed four distinct clusters, formed owing to different variants. The major cluster (cluster 4) is distinguished by mutations C313T, C5700A, G28881A are unique patterns and observed in 45% of samples. We thus report a newly emerging pattern of linked mutations. The predominance of these linked mutations suggests that they are likely a part of the viral fitness landscape. A novel and distinct pattern of mutations in the viral strains of each of the districts was observed. The Satara district viral strains showed mutations primarily at the 3′ end of the genome, while Nashik district viral strains displayed mutations at the 5′ end of the genome. Characterization of Pune strains showed that a novel variant has overtaken the other strains. Examination of the frequency of three mutations i.e., C313T, C5700A, G28881A in symptomatic versus asymptomatic patients indicated an increased occurrence in symptomatic cases, which is more prominent in females. The age-wise specific pattern of mutation is observed. Mutations C18877T, G20326A, G24794T, G25563T, G26152T, and C26735T are found in more than 30% study samples in the age group of 10-25. Intriguingly, these mutations are not detected in the higher age range 61-80. These findings portray the prevalence of unique linked mutations in SARS-CoV-2 in western India and their prevalence in symptomatic patients.

中文翻译：

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来自印度西部SARS-CoV-2基因组的系统生物学分析揭示了独特的连锁突变

印度已成为由SARS-CoV-2病毒引起的COVID-19大流行的第三重灾区。在这里，我们调查了印度西部（该国受影响最严重的地区）SARS-CoV-2的分子，系统发育和进化动力学。总共对90个基因组进行了测序。位于基因组5'UTR，Orf1a，Orf1b和Spike蛋白区域的四个核苷酸变体分别是C241T，C3037T，C14408T（Pro4715Leu）和A23403G（Asp614Gly），占主导地位和普遍存在（90％）。基因组的系统发育分析揭示了四个不同的簇，由于不同的变异而形成。主要簇（簇4）的特征在于突变C313T，C5700A，G28881A是独特的模式，在45％的样品中观察到。因此，我们报告了连锁突变的一种新兴模式。这些连锁突变的优势表明它们很可能是病毒适应性环境的一部分。在每个地区的病毒株中观察到一种新颖而独特的突变模式。Satara区病毒株主要在基因组3'端显示突变，而Nashik区病毒株则在基因组5'端显示突变。对Pune菌株的表征表明，一种新的变异体已经取代了其他菌株。对有症状患​​者和无症状患者中三个突变（即C313T，C5700A，G28881A）的频率进行检查，表明有症状病例的发生率增加，在女性中更为明显。观察到年龄的特定突变模式。变异C18877T，G20326A，G24794T，G25563T，G26152T，在10-25岁的年龄组中，超过30％的研究样本中发现了C26735T和C26735T。有趣的是，在较高的61-80岁年龄段中未检测到这些突变。这些发现描述了印度西部SARS-CoV-2中独特的连锁突变的患病率以及有症状患者的患病率。