Morley Valerie J, Sistrom Mark, Usme-Ciro Jose A, Remold Susanna K, Turner Paul E
Department of Ecology and Evolutionary Biology, Yale University, P.O. Box 208106, New Haven, CT, USA 06511.
Department of Ecology and Evolutionary Biology, Yale University, P.O. Box 208106, New Haven, CT, USA 06511,; School of Natural Sciences, University of California Merced, 5200 N. Lake Road, Merced, CA, USA 95343.
Virus Evol. 2016 Jan 20;2(1):vev022. doi: 10.1093/ve/vev022. eCollection 2016 Jan.
Virus populations may be challenged to evolve in spatially heterogeneous environments, such as mixtures of host cells that pose differing selection pressures. Spatial heterogeneity may select for evolved polymorphisms, where multiple virus subpopulations coexist by specializing on a narrow subset of the available hosts. Alternatively, spatial heterogeneity may select for evolved generalism, where a single genotype dominates the virus population by occupying a relatively broader host niche. In addition, the extent of spatial heterogeneity should influence the degree of divergence among virus populations encountering identical environmental challenges. Spatial heterogeneity creates environmental complexity that should increase the probability of differing adaptive phenotypic solutions, thus producing greater divergence among replicate virus populations, relative to counterparts evolving in strictly homogeneous host environments. Here, we tested these ideas using experimental evolution of RNA virus populations grown in laboratory tissue culture. We allowed vesicular stomatitis virus (VSV) lineages to evolve in replicated environments containing BHK-21 (baby hamster kidney) cells, HeLa (human epithelial) cells, or spatially heterogeneous host cell mixtures. Results showed that generalist phenotypes dominated in evolved virus populations across all treatments. Also, we observed greater variance in host-use performance (fitness) among VSV lineages evolved under spatial heterogeneity, relative to lineages evolved in homogeneous environments. Despite measurable differences in fitness, consensus Sanger sequencing revealed no fixed genetic differences separating the evolved lineages from their common ancestor. In contrast, deep sequencing of evolved VSV populations confirmed that the degree of divergence among replicate lineages was correlated with a larger number of minority variants. This correlation between divergence and the number of minority variants was significant only when we considered variants with a frequency of at least 10 per cent in the population. The number of lower-frequency minority variants per population did not significantly correlate with divergence.
病毒群体可能面临在空间异质性环境中进化的挑战，例如宿主细胞混合物会带来不同的选择压力。空间异质性可能会选择进化出多态性，即多个病毒亚群体通过专门利用可用宿主的一个狭窄子集而共存。或者，空间异质性可能会选择进化出通用性，即单一基因型通过占据相对更广泛的宿主生态位而主导病毒群体。此外，空间异质性的程度应会影响遇到相同环境挑战的病毒群体之间的分化程度。空间异质性创造了环境复杂性，这应该会增加出现不同适应性表型解决方案的概率，从而相对于在严格同质宿主环境中进化的对应群体，在重复的病毒群体中产生更大的分化。在这里，我们使用在实验室组织培养中生长的RNA病毒群体的实验进化来测试这些想法。我们让水疱性口炎病毒（VSV）谱系在含有BHK - 21（幼仓鼠肾）细胞、HeLa（人上皮）细胞或空间异质性宿主细胞混合物的重复环境中进化。结果表明，通用性表型在所有处理的进化病毒群体中占主导地位。此外，我们观察到，相对于在同质环境中进化的谱系，在空间异质性条件下进化的VSV谱系之间在宿主利用性能（适应性）方面存在更大的差异。尽管适应性存在可测量的差异，但桑格测序结果显示，进化谱系与其共同祖先之间没有固定的遗传差异。相比之下，对进化后的VSV群体进行深度测序证实，重复谱系之间的分化程度与更多的少数变体相关。只有当我们考虑群体中频率至少为10%的变体时，这种分化与少数变体数量之间的相关性才显著。每个群体中低频少数变体的数量与分化没有显著相关性。
