Data_Sheet_1_The SARS-CoV-2 differential genomic adaptation in response to varying UVindex reveals potential genomic resources for better COVID-19 diagnosis and prevention.docx

Coronavirus disease 2019 (COVID-19) has been a pandemic disease reported in almost every country and causes life-threatening, severe respiratory symptoms. Recent studies showed that various environmental selection pressures challenge the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infectivity and, in response, the virus engenders new mutations, leading to the emergence of more virulent strains of WHO concern. Advance prediction of the forthcoming virulent SARS-CoV-2 strains in response to the principal environmental selection pressures like temperature and solar UV radiation is indispensable to overcome COVID-19. To discover the UV-solar radiation-driven genomic adaption of SARS-CoV-2, a curated dataset of 2,500 full-grade genomes from five different UVindex regions (25 countries) was subjected to in-depth downstream genome-wide analysis. The recurrent variants that best respond to UV-solar radiations were extracted and extensively annotated to determine their possible effects and impacts on gene functions. This study revealed 515 recurrent single nucleotide variants (rcntSNVs) as SARS-CoV-2 genomic responses to UV-solar radiation, of which 380 were found to be distinct. For all discovered rcntSNVs, 596 functional effects (rcntEffs) were detected, containing 290 missense, 194 synonymous, 81 regulatory, and 31 in the intergenic region. The highest counts of missense rcntSNVs in spike (27) and nucleocapsid (26) genes explain the SARS-CoV-2 genomic adjustment to escape immunity and prevent UV-induced DNA damage, respectively. Among all, the most commonly observed rcntEffs were four missenses (RdRp-Pro327Leu, N-Arg203Lys, N-Gly204Arg, and Spike-Asp614Gly) and one synonymous (ORF1ab-Phe924Phe) functional effects. The highest number of rcntSNVs found distinct and were uniquely attributed to the specific UVindex regions, proposing solar-UV radiation as one of the driving forces for SARS-CoV-2 differential genomic adaptation. The phylogenetic relationship indicated the high UVindex region populating SARS-CoV-2 as the recent progenitor of all included samples. Altogether, these results provide baseline genomic data that may need to be included for preparing UVindex region-specific future diagnostic and vaccine formulations.

2019冠状病毒病（Coronavirus disease 2019, COVID-19）已成为在全球几乎所有国家均有报告的大流行性疾病，可引发危及生命的重症呼吸道症状。近期研究表明，各类环境选择压力会对严重急性呼吸综合征冠状病毒2（severe acute respiratory syndrome coronavirus-2, SARS-CoV-2）的感染性造成挑战，病毒为应对此类压力会产生新的突变，进而出现受世界卫生组织（World Health Organization, WHO）关注的高致病性毒株。针对温度、太阳紫外线辐射等主要环境选择压力，提前预测即将出现的高致病性SARS-CoV-2毒株，对于防控COVID-19而言不可或缺。为探究太阳紫外线辐射驱动的SARS-CoV-2基因组适应性，研究人员对来自5个不同紫外线指数（Ultraviolet Index, UVindex）区域（涵盖25个国家）、包含2500条高质量全基因组的精心整理数据集，开展了深入的全基因组下游分析。研究人员提取出对太阳紫外线辐射响应最佳的高频变异位点，并进行了全面注释，以明确其对基因功能可能产生的作用与影响。本研究共鉴定出515个作为SARS-CoV-2对太阳紫外线辐射基因组响应的高频单核苷酸变异（recurrent single nucleotide variants, rcntSNVs），其中380个为独特变异。针对所有鉴定出的rcntSNVs，研究人员共检测到596种功能效应（rcntEffs），其中包括290个错义突变、194个同义突变、81个调控区变异以及31个基因间区变异。刺突蛋白（spike）基因与核衣壳蛋白（nucleocapsid）基因中的错义rcntSNVs数量最多，分别为27个和26个，这分别对应SARS-CoV-2为逃避免疫识别以及抵御紫外线诱导的DNA损伤所进行的基因组适应性调整。在所有功能效应中，最常见的为4种错义突变效应：RNA依赖的RNA聚合酶（RNA-dependent RNA polymerase, RdRp）Pro327Leu、核衣壳蛋白（N）Arg203Lys、核衣壳蛋白（N）Gly204Arg以及刺突蛋白（Spike）Asp614Gly，以及1种同义突变效应：开放阅读框1ab（ORF1ab）Phe924Phe。有数量最多的独特rcntSNVs仅归属于特定的紫外线指数区域，这表明太阳紫外线辐射是推动SARS-CoV-2产生差异化基因组适应性的驱动力之一。系统发育关系分析显示，来自高紫外线指数区域的SARS-CoV-2毒株是本次纳入所有样本的近代祖先株。综上，本研究结果提供了基线基因组数据，这些数据或可用于制定针对特定紫外线指数区域的未来诊断试剂与疫苗研发方案。