Life on the 'mild' side: adaptation of an extremophile archaeon to a mesophilic lifestyle

极端微生物已经进化出了应对恶劣环境的特殊适应能力。在这样的条件下保持基因组的完整性需要高的DNA复制保真度和修复系统来防止基因组退化。然而，这些系统可能会阻碍产生适应中温条件所需的新的遗传变异。该项目的目的是确定在极端嗜热古生物适应中温条件(即环境降温和碱化)过程中发生的进化转变和适应限制。我们将表征Sulfolobus acidocaldarius的中温适应性，Sulfolobus acidocaldarius是一种嗜热嗜酸古生菌，最适生长在75-80摄氏度和pH 2-3。我们将首先评估嗜酸葡萄球菌在中温条件下是否有突变限制。然后，我们将使用实验室实验进化来逐渐使嗜酸葡萄球菌适应温度降低和pH升高，并使用基因组测序来识别关键的适应性突变。最后，我们将评估适应中温条件是否在突变率增加之前或与之相关。我们假设进化中的‘增强’突变将涉及酸链球菌所拥有的一个或多个高度专门化的DNA修复和复制保真系统中的一个或多个功能丧失或功能降低的变异。这项工作将首次确定环境特有的适应和支持中温适应的进化机制。这将阐明极端生物和中温生物的生活方式之间的转变，在全球和微观尺度上，在不断变化的环境条件下，地球生命演化史的早期可能就发生了这种转变。

Extremophilic organisms have evolved specialised adaptations for coping with harsh environments. Maintaining genomic integrity under such conditions requires high DNA replication fidelity and repair systems to prevent genome degradation. However, these systems may hinder the generation of novel genetic variation required to adapt to mesophilic conditions. The Aim of this project is to identify evolutionary transitions, and constraints on adaptation, that occur during adaptation of an extremophile archaeon to mesophilic conditions (i.e. environmental cooling and alkalinization). We will characterise mesophilic adaptation in Sulfolobus acidocaldarius, a thermoacidophilic archaeon with optimal growth at 75-80 degrees Celsius and pH 2-3. We will first assess whether S. acidocaldarius is mutation limited under mesophilic conditions. We will then use laboratory experimental evolution to gradually adapt S. acidocaldarius to decreased temperature and increased pH, and use genomic sequencing to identify key adaptive mutations. Finally, we will assess whether adapting to mesophilic conditions was preceded by, or associated with, an increase in mutation rate. We hypothesise that evolutionary 'potentiating' mutations will involve loss-of-function or function-reducing variation in one or more of the highly-specialised DNA repair and replication fidelity systems possessed by S. acidocaldarius. This work will determine, for the first time, both the environment-specific adaptations and the evolutionary mechanisms underpinning mesophilic adaptation. This will shed light on transitions between extremophile and mesophile lifestyles, as may have occurred early in the evolutionary history of life on Earth under changing environmental conditions, on both global and microscopic scales.