新的见解乙型肝炎病毒的进化速率在不同尺度的生物

StephenW

New Insights into the Evolutionary Rate of Hepatitis B Virus at Different Biological Scales

    You-Yu Lin a,
    Chieh Liu b,
    Wei-Hung Chien c*,
    Li-Ling Wu c,
    Yong Tao d,
    Dafei Wu d,
    Xuemei Lu d,
    Chia-Hung Hsieh e,
    Pei-Jer Chen c,
    Hurng-Yi Wang c,f,g,
    Jia-Horng Kao c and
    Ding-Shinn Chen c,h

    aDepartment of Life Science, National Taiwan University, Taipei, Taiwan
    bDepartment of Microbiology, National Taiwan University, Taipei, Taiwan
    cGraduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
    dLaboratory of Disease Genomics and Individualized Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China
    eDepartment of Forestry and Nature Conservation, Chinese Culture University, Taipei, Taiwan
    fInstitute of Ecology and Evolution, National Taiwan University, Taipei, Taiwan
    gResearch Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei, Taiwan
    hGenomics Research Center, Academia Sinica, Taipei, Taiwan

    J.-H. J. Ou, Editor

- Author Affiliations
ABSTRACT

The evolutionary rates of hepatitis B virus (HBV) estimated using contemporary sequences are 102 to 104 times higher than those derived from archaeological and genetic evidence. This discrepancy makes the origin of HBV and the time scale of its spread, both of which are critical for studying the burden of HBV pathogenicity, largely unresolved. To evaluate whether the dual demands (i.e., adaptation within hosts and colonization between hosts) of the viral life cycle affect this conundrum, the HBV quasispecies dynamics within and among hosts from a family consisting of a grandmother, her 5 children, and her 2 granddaughters, all of whom presumably acquired chronic HBV through mother-to-infant transmission, were examined by PCR cloning and next-generation sequencing methods. We found that the evolutionary rate of HBV between hosts was considerably lower than that within hosts. Moreover, the between-host substitution rates of HBV decreased as transmission numbers between individuals increased. Both observations were due primarily to changes at nonsynonymous rather than synonymous sites. There were significantly more multiple substitutions than expected for random mutation processes, and 97% of substitutions were changed from common to rare amino acid residues in the database. Continual switching between colonization and adaptation resulted in a rapid accumulation of mutations at a limited number of positions, which quickly became saturated, whereas substitutions at the remaining regions occurred at a much lower rate. Our study may help to explain the time-dependent HBV substitution rates reported in the literature and provide new insights into the origin of the virus.

IMPORTANCE It is known that the estimated hepatitis B virus (HBV) substitution rate is time dependent, but the reason behind this observation is still elusive. We hypothesize that owing to the small genome size of HBV, transmission between hosts and adaptation within hosts must exhibit high levels of fitness trade-offs for the virus. By studying the HBV quasispecies dynamics for a chain of sequentially infected transmissions within a family, we found the HBV substitution rate between patients to be negatively correlated with the number of transmissions. Continual switching between hosts resulted in a rapid accumulation of mutations at a limited number of genomic sites, which quickly became saturated in the short term. Nevertheless, substitutions at the remaining regions occurred at a much lower rate. Therefore, the HBV substitution rate decreased as the divergence time increased.

StephenW

新的见解乙型肝炎病毒的进化速率在不同尺度的生物

    你宇林一，
    杰柳B，
    伟洪干C *
    李泠五C，
    雍陶D，
    达菲武D，
    雪梅路D，
    嘉鸿谢E，
    裴哲陈C，
    Hurng，易挖嗯C，F，G，
    佳鸿花王c和
    鼎希恩陈C，H

    生命科学，国立台湾大学，台北，台湾aDepartment
    微生物学，国立台湾大学，台北，台湾bDepartment
    临床医学国立台湾大学cGraduate研究所，台北，台湾
    疾病基因组学与个体化用药，基因组研究所北京，中国的院士，北京，中国的dLaboratory
    林业和自然保护，中国文化大学，台北，台湾eDepartment
    生态与进化，国立台湾大学，台北，台湾fInstitute
    国立台湾大学gResearch中心发育生物学和再生医学，台北，台湾
    hGenomics研究中心，中央研究院，台北，台湾

    J.-H. J.欧，编辑器

- 作者所属机构
摘要

估计使用当代序列是102至104倍，比那些来自考古学和遗传学证据来自更高乙型肝炎病毒（HBV）的进化速率。这种差异使HBV的起源和它的传播的时间尺度，这两者是研究HBV致病的负担，主要是未解决的关键。为了评估是否双重要求（即主机和主机之间的殖民内适应）病毒生命周期的影响这一难题，并在一个由奶奶从一个家庭主机间的HBV准种的动态，她的5个孩子，她的孙女2 ，所有的人大概是通过母亲向婴儿传播获得的慢性HBV，经PCR克隆和下一代测序方法研究。我们发现，乙肝病毒的主机之间的进化速度比主机内的要低得多。此外，乙肝病毒的宿主之间的替代率降低个人之间传输的数字增加。双方的意见，主要是因为在非同义，而不是网站的代名词变化。有对随机突变的过程比预期的和替换的97％是由共同改变为罕见的氨基酸残基在数据库显著更多个取代。殖和适应之间不断切换导致的突变，在有限数量的位置中，迅速成为饱和一快速积累，而取代在剩余区域出现在低得多的速率。我们的研究可能有助于解释文献报道的时间依赖性HBV替代率，并提供新的见解病毒的起源。

重要性已知的是所估计的乙肝病毒（HBV）置换率是依赖于时间的，但后面这种观察的原因仍然是难以捉摸的。我们推测，由于HBV的主机和适应之间的小基因组大小，传输主机内必须表现出对病毒的高水平的健身权衡。通过研究HBV准种动力学为家庭内的链顺序地感染传输的，我们发现病人之间的乙肝置换率是负与发送次数有关。主机之间连续切换导致的突变在基因组位点，从而迅速变得饱和，在短期内的有限数量的迅速积累。然而，取代于剩余区域出现在低得多的速率。因此，HBV的取代率降低的发散时间的增加。

王震宇

这不是胡说八道么！

StephenW

回复 王震宇 的帖子

此类的研究非常有意义 - HBV的长期进化.是变得更加良性的？

我不理解这摘要, 但我知道你是胡说八道么.