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Very large hidden genetic diversity in one single tumor:evidence for tumors-in-tumor

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National Science Review 2022年第12期9卷 124-134页

作者： Bingjie Chen Xianrui Wu yongsen ruan Yulin Zhang Qichun Cai Luis Zapata Chung-I Wu Ping Lan Haijun Wen State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University GMU-GIBH Joint School of Life Sciences Guangzhou Medical University Evolutionary Genomics and Modelling Lab Centre for Evolution and Cancer The Institute of Cancer Research Department of Colorectal Surgery The Sixth Affiliated Hospital Sun Yat-sen University Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases The Sixth Affiliated Hospital Sun Yat-sen University Cancer Center Clifford HospitalJinan University

Despite the concern of within-tumor genetic diversity,this diversity is in fact limited by the kinship among cells in the ***,genomic studies have amply supported the ’Nowell dogma’ whereby cells of the same tumor descend from a single progenitor *** parallel,genomic data also suggest that the diversity could be> 10-fold larger if tumor cells are of multiple *** develop an evolutionary hypothesis that a single tumor may often harbor multiple cell clones of independent origins,but only one would be large enough to be *** test the hypothesis,we search for independent tumors within a larger one(or tumors-in-tumor).Very high density sampling was done on two cases of colon *** 1 indeed has 13 independent clones of disparate sizes,many having heavy mutation burdens and potentially highly *** Case 2,despite a very intensive search,only two small independent clones could be *** two cases show very similar movements and metastasis of the dominant *** initially move actively in the expanding tumor but become nearly immobile in late *** conclusion,tumors-in-tumor are plausible but could be very demanding to *** their small sizes,they can enhance the within-tumor diversity by orders of *** increases may contribute to the missing genetic diversity associated with the resistance to cancer therapy.

关键词： intratumoral heterogeneity tumor origins cancer evolution tumors-in-tumor

The twin-beginnings of COVID-19 in Asia and Europe—one prevails quickly

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National Science Review 2022年第4期9卷 51-59页

作者： yongsen ruan Haijun Wen Mei Hou Ziwen He Xuemei Lu Yongbiao Xue Xionglei He Ya-Ping Zhang Chung-I Wu State Key Laboratory of Biocontrol School of Life SciencesSouthern Marine Science and Engineering Guangdong Laboratory (Zhuhai)Sun Yat-sen University Department of Ecology and Evolution University of Chicago State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of Sciences Beijing Institute of Genomics Chinese Academy of Sciencesand China National Centre for Bioinformation

In the spread of SARS-C oV-2,there have been multiple waves of replacement between strains,each of which having a distinct set of *** first wave is a group of four mutations(C241 T,C3037 T,C14408 T and A23403 G [this being the amino acid change D614 G];all designated 0 to 1 below).This DG(D614 G) group,fixed at the start of the pandemic,is the foundation of all subsequent waves of ***,the DG group is absent in early Asian samples but present(and likely common) in Europe from the *** data show that the high fitness of DG1111 requires the synergistic effect of all four ***,the European strains would have had no time to evolve the four DG mutations(0 to1),had they come directly from the early Asian DG0000 *** likely,the European DG1111 strain had acquired the highly adaptive DG mutations in pre-pandemic Europe and had been spreading in parallel with the Asian *** recent reports further support this twin-beginning *** was a period of two-way spread between Asia and Europe but,by May 2020,the European strains had supplanted the Asian strains *** large-scale replacement of one set of mutations for another has since been replayed many times as COVID-19 progresses.

关键词： SARS-CoV-2 COVID-19 D614G twin-beginnings fitness advantage

On the founder effect in COVID-19 outbreaks:how many infected travelers may have started them all?

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National Science Review 2021年第1期8卷 30-39页

作者： yongsen ruan Zhida Luo Xiaolu Tang Guanghao Li Haijun Wen Xionglei He Xuemei Lu Jian Lu Chung-I Wu State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University State Key Laboratory of Protein and Plant Gene Research Center for Bioinformatics School of Life SciencesPeking University CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of Genomics Chinese Academy of Sciences State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyCenter for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences

How many incoming travelers（I;at time 0, equivalent to the ‘founders’ in evolutionary genetics） infected with SARS-CoV-2 who visit or return to a region could have started the epidemic of that region? I;would be informative about the initiation and progression of epidemics. To obtain I;, we analyze the genetic divergence among viral populations of different regions. By applying the ‘individual-output’ model of genetic drift to the SARS-CoV-2 diversities, we obtain I; 0） or the fitness of the variants. With such a tiny trickle of human movement igniting many outbreaks, the crucial stage of repressing an epidemic in any region should,therefore, be the very first sign of local contagion when positive cases first become identifiable. The implications of the highly ‘portable’ epidemics, including their early evolution prior to any outbreak, are explored in the companion study（ruan et al., personal communication）.

关键词： SARS-CoV-2 COVID-19 population genetics genetic drift founder effect

A theoretical exploration of the origin and early evolution of a pandemic

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Science Bulletin 2021年第10期66卷 1022-1029,M0004页

作者： yongsen ruan Haijun Wen Xionglei He Chung-I Wu State Key Laboratory of Biocontrol School of Life SciencesSun Yat-sen UniversityGuangzhou 510275China

A virus that can cause a global pandemic must be highly adaptive to human *** adaptation is not likely to have emerged suddenly but,instead,may have evolved step by step with each step favored by natural *** is thus necessary to develop a theory about the origin in order to guide the ***,we propose such a model whereby evolution occurs in both the virus and the hosts(where the evolution is somatic;i.e.,in the immune system).The hosts comprise three groups–the wild animal hosts,the nearby human population,and farther-away human *** theory suggests that the conditions under which the pandemic has initially evolved are:(i)an abundance of wild animals in the place of origin(PL_(0));(ii)a nearby human population of low density;(iii)frequent and long-term animal-human contacts to permit step-by-step evolution;and(iv)a level of herd immunity in the animal and human *** this model,the evolving virus may have regularly spread out of PL_(0) although such invasions often fail,leaving sporadic cases of early *** place of the first epidemic(PL_(1)),where humans are immunologically naïve to the virus,is likely a distance away from PL_(0).Finally,this current model is only a first attempt and more theoretical models can be expected to guide the search for the origin of SARS-CoV-2.

关键词： SARS-CoV-2 COVID-19 Origin Epidemics Viral invasion Herd immunity

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Dynamic global analysis of transcription reveals the role of mi RNAs in synergistic stabilization of gene expression

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Science Bulletin 2020年第24期65卷 2130-2140,M0006页

作者： Fuqiang Ma Guang-An Lu Qingjian Chen yongsen ruan Xin Li Xuemei Lu Chunyan Li School of Life Sciences Sun Yat-sen University.Guangzhou 510275China Beijing Advanced Innovation Center for Big Data-Based Precision Medicine School of Medicine and Engineeringand Key Laboratory of Big Data-Based Precision Medicine(Ministry of Industry and Information Technology)Beihang UniversityBeijing 100191China State Key Laboratory of Genetic Resources and Evolution&CAS Center for Excellence in Animal Evolution and Genetics Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Buffering exogenous perturbation is crucial to maintain transcriptional homeostasis during *** mi RNAs have been speculated to play a role in stability maintenance, previous studies seeking to check this conjecture focused on measurements of transcript levels at steady state or involved individual mi RNA targets. We measured whole-genome expression dynamics by introducing a transient perturbation and establishing a perturbation and recovery system in Drosophila larvae. We inhibited all transcription and assayed transcriptomes at several time points during recovery from inhibition. We performed these experiments in the wild type and mi RNA-deficient genetic backgrounds. Consistent with theories about mi RNAs’ function in stabilizing the transcriptome, we find that attenuating mi RNA expression leads to weak impairment in degradation of targets but strong destabilization of target genes when transcription is re-activated. We further fitted a model that captures the essential aspects of transcription dynamics in our experiments and found that the mi RNA target transcripts uniformly overshoot the original steady state as they recover from a general inhibition of transcription if global mi RNA levels are reduced. Collectively, our results provide experimental evidence for the idea that mi RNAs act cumulatively to stabilize the transcriptional regulatory network. We therefore found a promising approach to assess the effect of these molecules on transcription dynamics.

关键词： miRNAs Transcriptome Perturbation Stability Synergistic effects

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On the origin of SARS-CoV-2——The blind watchmaker argument

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Science China(Life Sciences) 2021年第9期64卷 1560-1563页

作者： Chung-I Wu Haijun Wen Jian Lu Xiao-dong Su Alice CHughes Weiwei Zhai Chen Chen Hua Chen Mingkun Li Shuhui Song Zhaohui Qian Qihui Wang Bingjie Chen Zixiao Guo yongsen ruan Xuemei Lu Fuwen Wei Li Jin Le Kang Yongbiao Xue Guoping Zhao Ya-Ping Zhang State Key Laboratory of Biocontrol School of Life SciencesSun Yat-sen UniversityGuangzhou 510275China State Key Laboratory of Protein and Plant Gene Research Center for BioinformaticsSchool of Life SciencesPeking UniversityBeijing 100871China Landscape Ecology Group Center for Integrative ConservationXishuangbanna Tropical Botanical GardenChinese Academy of SciencesMengla 666303China Key Laboratory of Zoological Systematics and Evolution Institute of ZoologyChinese Academy of SciencesBeijing 100101China Biomedical Innovation Center Beijing Shijitan HospitalCapital Medical UniversityBeijing 100038China Beijing Institute of Genomics Chinese Academy of Sciencesand China National Centre for BioinformationBeijing 100101China Institute of Pathogen Biology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100176China CAS Key Laboratory of Pathogen Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Genetic Resources and Evolution Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China CAS Key Laboratory of Animal Ecology and Conservation Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China MOE Key Laboratory of Contemporary Anthropology Department of Anthropology and Human GeneticsSchool of Life SciencesFudan UniversityShanghai 200433China State Key Laboratory of Integrated Management of Pest Insects and Rodents Institute of ZoologyChinese Academy of SciencesBeijing 100101China Key Laboratory of Synthetic Biology Institute of Plant Physiology and EcologyShanghai Institutes for Biological SciencesChinese Academy of SciencesShanghai 200032China

In the comparison with SARS-CoVof 2003,SARS-CoV-2 is extremely well adapted to the human populations and its adaptive shift from the animal host to humans must have been even more *** the blind watchmaker argument,such an adaptive shift can only happen prior to the onset of the current pandemic and with the aid of step-by-step selection.

关键词： argument origin adapted

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