Long-term evolution and short-term adaptation of microbiota strains and sub-strains

Long-term evolution and short-term adaptation of microbiota strains and sub-strainsCatherine Mooser1,2,9, Bahtiyar Yilmaz1,2,9, Irene Keller1,3,9, Lars Bosshard3,8, Jakob Zimmermann1,2, Tobias Fuhrer4, Mercedes Gomez de Agüero1,2, Heidi Tschanz-Lischer1,3, Hai Li1,2, Julien P. Limenitakis1,2, Wolf-Dietrich Hardt5, Kathy D. McCoy1,2, Bärbel Stecher6,7, Laurent Excoffier3,8, Uwe Sauer4, Stephanie C. Ganal-Vonarburg1,2, Andrew J. Macpherson1,2,*SUMMARYStable animal models are essential to reproducibly investigate mechanisms of host-microbial mutualism. Isobiotic mice, with an identical stable microbiota composition, potentially allow models of host-microbial mutualism to be studied over time and between different laboratories. To understand how microbiota evolution occurs in these models, we carried out a 6-year experiment in mice colonized with 12 representative fully-sequenced taxa. External introduction of new taxa was strictly avoided to distinguish microbiota evolution without confounding immigrant microbes. Increased non-synonymous to synonymous mutation fixation rates (dN/dS > 1) indicated positive selection in multiple taxa, particularly for genes annotated for nutrient acquisition or replication. Microbial sub-strains that had evolved within a single taxon were able to stably coexist, consistent with niche partitioning of ecotypes in the complex intestinal environment. Dietary shifts triggered rapid transcriptional adaptation to macronutrient and micronutrient changes in individual taxa and alterations in taxa biomass. The proportions of different sub-strains were also rapidly altered after dietary shift. This indicates that microbial taxa adapt to changes in the intestinal environment by long-term genomic positive selection and short-term effects of transcriptional reprogramming and adjustments in sub-strain proportions.微生物群菌株与亚菌株的长期演化及短期适应 Catherine Mooser1,2,9, Bahtiyar Yilmaz1,2,9, Irene Keller1,3,9, Lars Bosshard3,8, Jakob Zimmermann1,2, Tobias Fuhrer4, Mercedes Gomez de Agüero1,2, Heidi Tschanz-Lischer1,3, Hai Li1,2, Julien P. Limenitakis1,2, Wolf-Dietrich Hardt5, Kathy D. McCoy1,2, Bärbel Stecher6,7, Laurent Excoffier3,8, Uwe Sauer4, Stephanie C. Ganal-Vonarburg1,2, Andrew J. Macpherson1,2,* 摘要 稳定的动物模型是可重复探究宿主-微生物共生机制的必要条件。同微生物群小鼠（isobiotic mice）具有完全一致的稳定微生物群组成，有望实现跨时间、跨不同实验室的宿主-微生物共生模型研究。为阐明此类模型中微生物群的演化规律，我们对定殖有12种已完成全基因组测序的代表性微生物类群的小鼠开展了为期6年的实验。实验全程严格避免外源类群的引入，以排除外来微生物的干扰，从而单纯研究微生物群的演化过程。 非同义突变与同义突变的固定速率比值（dN/dS > 1）升高，提示多个微生物类群发生了正向选择，尤其在注释为营养获取或复制相关的基因中更为显著。单一类群内演化产生的微生物亚菌株可稳定共存，这与复杂肠道环境中生态型的生态位分化现象相符。饮食结构改变可快速引发单个微生物类群对宏量营养素与微量营养素变化的转录组适应，并伴随类群生物量的改变；饮食改变后，不同亚菌株的占比同样会快速发生变化。上述结果表明，微生物类群通过两种方式适应肠道环境变化：一是长期的基因组正向选择，二是转录重编程与亚菌株占比调整所介导的短期适应性调控。