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Reconstructing early transmission networks of SARS-CoV-2 using a genomic mutation model

Zoological Research 2023年第3期44卷 494-504页

作者： Chao-Yuan Cheng Zhi-Bin Zhang State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijing 100101China CAS Center for Excellence in Biotic Interactions University of Chinese Academy of SciencesBeijing 100049China

The coronavirus disease 2019(COVID-19)pandemic has greatly damaged human society,but the origins and early transmission patterns of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)pathogen remain unclear.Here,we reconstructed the transmission networks of SARS-CoV-2 during the first three and six months since its first report based on ancestor-offspring relationships using BANAL-52-referenced mutations.We explored the position(i.e.,root,middle,or tip)of early detected samples in the evolutionary tree of SARS-CoV-2.In total,6799 transmission chains and 1766 transmission networks were reconstructed,with chain lengths ranging from 1-9 nodes.The root node samples of the 1766 transmission networks were from 58 countries or regions and showed no common ancestor,indicating the occurrence of many independent or parallel transmissions of SARS-CoV-2 when first detected(i.e.,all samples were located at the tip position of the evolutionary tree).No root node sample was found in any sample(n=31,all from the Chinese mainland)collected in the first 15 days from 24 December 2019.Results using six-month data or RaTG13-referenced mutation data were similar.The reconstruction method was verified using a simulation approach.Our results suggest that SARS-CoV-2 may have already been spreading independently worldwide before the outbreak of COVID-19 in Wuhan,China.Thus,a comprehensive global survey of human and animal samples is essential to explore the origins of SARS-CoV-2 and its natural reservoirs and hosts.

关键词： SARS-CoV-2 Transmission chain Transmission network Ancestor-offspring relationship De novo mutation Back mutation Secondary mutation

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HUMAN MITOCHONDRIAL tRNA mutationS IN MATERNALLY INHERITED DEAFNESS

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Journal of Otology 2013年第1期8卷 44-50页

作者： ZHENG Jing GONG Sha-sha TANG Xiao-wen ZHU Yi GUAN Min-xin Department of Genetics College of Life SciencesZhejiang University Attardi Institute of Mitochondrial Biomedicine Wenzhou Medical University

mutations in mitochondrial tRNA genes have been shown to be associated with maternally inherited syn-dromic and non-syndromic deafness. Among those, mutations such as tRNALeu(UUR) 3243A>G associated with syndromic deafness are often present in heteroplasmy, and the non-syndromic deafness-associated tRNA mu-tations including tRNASer(UCN) 7445A>G are often in homoplasmy or in high levels of heteroplasmy. These tRNA mutations are the primary factors underlying the development of hearing loss. However, other tRNA mutations such as tRNAThr 15927G>A and tRNASer(UCN) 7444G>A are insufficient to produce a deafness phe-notype, but always act in synergy with the primary mitochondrial DNA mutations, and can modulate their phenotypic manifestation. These tRNA mutations may alter the structure and function of the corresponding mitochondrial tRNAs and cause failures in tRNAs metabolism. Thereby, the impairment of mitochondrial protein synthesis and subsequent defects in respiration caused by these tRNA mutations, results in mitochon-drial dysfunctions and eventually leads to the development of hearing loss. Here, we summarized the deaf-ness-associated mitochondrial tRNA mutations and discussed the pathophysiology of these mitochondrial tRNA mutations, and we hope these data will provide a foundation for the early diagnosis, management, and treatment of maternally inherited deafness.

关键词： deafness mitochondria tRNA primary mutation Secondary mutation maternally inherited

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