Collaborative Research: Origin of multicellular complexity in experimentally-evolved Saccharomyces cerevisiae

复杂的多细胞生命是如何从数十亿年来定义地球生命的单细胞微生物中产生的？多细胞生物的兴起推动了生命的深刻多样化，从根本上改变了地球的生态，但人们对这一重大进化转变是如何发生的知之甚少。这主要是由于大多数多细胞谱系都是古老的，而这种转变的早期步骤已经被灭绝所掩盖。pi通过开发一种新的实验室系统，通过实验在贝克酵母中进化简单的多细胞生物，克服了这一限制。经过数千代的实验室进化，这些集群形成的“雪花酵母”进化出一套多细胞适应性，包括更大的集群大小，更高的细胞程序性死亡率，以及更流体动力学的特征。pi将使用这个模型系统来研究新的多细胞性状是如何在进化中产生的，并将确定一个基本的发育机制，即大多数多细胞生物所经历的单细胞瓶颈（例如，一个受精卵），是否提高了自然选择作用于这些涌现的多细胞性状的能力。这项跨学科的工作利用了实验进化，下一代测序，分子遗传学，共聚焦显微镜，图像分析和数学建模的尖端技术。通过阐明向多细胞生物进化过渡的最初步骤，提出的研究将有助于解决一个对生物学至关重要的突出问题。生物复杂性的进化在教学上仍然具有挑战性，尤其是在高中阶段。该奖项将支持开发一种适合高中和大学课堂的新型实验室模块，在该模块中，学生使用雪花酵母和计算机模拟来研究多细胞生物的进化。pi将举办夏季校内研讨会，培训亚特兰大地区的教师使用该课程。最近的实验表明，单细胞生物很容易进化成多细胞集群，但对细胞集群随后如何进化成更大的多细胞复杂性知之甚少。提出的研究通过提出以下问题直接解决了这一问题：当突变和重组只能直接影响细胞水平的表型时，多细胞性状是如何在进化中出现的？早期的发育机制能否进化为促进这些涌现的多细胞特征的选择？发育功能的基因是如何招募的？新的多细胞适应性是如何整合到整个生物体的形态和功能中的？回答上述问题将为多细胞复杂性的进化起源提供基本的见解，并将为其他主要进化转变的类似研究提供理论基础。雪花酵母是这项工作的理想实验系统：pi已经进化出了大量的形态学新颖性，雪花的生长形式在数学上是可处理的，并且已经由pi建模，并且为酵母开发的广泛的生物信息学和分子遗传学工具允许合成具有精确定义特性的多细胞菌株。

How did complex multicellular life arise from the single-celled microorganisms that defined life on Earth for billions of years? The rise of multicellular organisms drove a profound diversification of life that fundamentally changed Earth's ecology, yet little is known about how this major evolutionary transition occurred. This is largely due to the fact that most multicellular lineages are ancient, and early steps in this transition have been obscured by extinction. The PIs have overcome this limitation by developing a novel laboratory system, experimentally evolving simple multicellularity in Baker's yeast. Over thousands of generations of laboratory evolution, these cluster-forming 'snowflake yeast' evolve a suite of multicellular adaptations, including larger cluster size, an elevated rate of programmed cell death, and a more hydrodynamic profile. The PIs will use this model system to examine how novel multicellular traits arise in evolution, and will determine whether a fundamental developmental mechanism, the single-celled bottleneck that most multicellular organisms pass through (e.g., a single fertilized egg), improves the ability of natural selection to act on these emergent multicellular traits. This interdisciplinary work utilizes cutting-edge techniques in experimental evolution, next generation sequencing, molecular genetics, confocal microscopy, image analysis, and mathematical modeling. By illuminating the earliest steps in the evolutionary transition to multicellularity, the proposed research will help resolve an outstanding problem of central importance to biology. The evolution of biological complexity remains challenging to teach, particularly at the high school level. This award will support the development of a novel lab module, suitable for both high school and college classes, in which students use snowflake yeast and computer simulations to examine the evolution of multicellularity. The PIs will hold summer on-campus workshops to train teachers in the Atlanta area to use this curricula.Recent experiments have shown that unicellular organisms readily evolve to form multi-celled clusters, but little is known about how cellular clusters subsequently evolve greater multicellular complexity. The proposed research addresses this subject directly by asking the following questions: How do multicellular traits arise in evolution when mutation and recombination can only directly affect cell-level phenotype? Can early developmental mechanisms evolve to facilitate selection on these emergent multicellular traits? How are genes recruited for developmental functionality, and how are novel multicellular adaptations integrated into overall organism form and function? Answering the above questions will provide fundamental insight into the evolutionary origins of multicellular complexity, and will provide a theoretical foundation for similar investigations in other major evolutionary transitions. Snowflake yeast are an ideal experimental system for this work: the PIs have already evolved substantial morphological novelty, the snowflake growth form is mathematically tractable and has already been modeled by the PIs, and the extensive bioinformatic and molecular genetic tools developed for yeast allows for synthetic construction of multicellular strains with precisely defined properties.