Cellular Cooperation and Cheating: an Experimental and Mathematical Analysis

描述（由申请人提供） 翻译后摘要：合作是广泛的，并已被假定为推动重大转变的演变。一个合作者付出成本来造福他人，当得到回报时，它获得了净收益。然而，达尔文的选择倾向于“骗子”，他们消耗利益而不付出公平的代价。许多合作系统已经发展出复杂的作弊者识别/排除机制。如何从简单的合作系统演变出抵制作弊的机制？为了解决这个问题，我创建了一个遗传上易于处理的合作系统，可以观察到它从一开始就逐步发展到稳定性增加。它由两种工程非交配酵母菌株组成-一种红色荧光R菌株需要腺嘌呤并释放赖氨酸，一种黄色荧光Y菌株需要赖氨酸并释放腺嘌呤。我注意到：该系统是有活力的-在没有腺嘌呤和赖氨酸补充物的情况下，在宽范围的条件下，能够从低密度生长到饱和;系统活力要求可以从两种合作菌株的生长、死亡和代谢特性计算;该系统进化出增加的系统活力：系统活力所需的最小细胞密度降低了100倍。我的团队将：发现增加系统可行性的变化的多样性。有利于合作的改变必须通过使自己和/或伙伴受益来发挥作用。将测量进化菌株的特性，并量化其对加强合作的相对贡献。 决定了对作弊者的容忍机制在引入消耗但不释放代谢物的作弊者后，我们将选择具有增加的作弊者耐受性的合作者/作弊者共培养物并描述机制。 探讨空间结构稳定合作的可能性。我们将比较在一个良好混合的液体培养（无空间结构）与琼脂垫（有空间结构）上的合作系统的可行性要求和作弊者容忍度。我们希望定量地了解合作和欺骗容忍度的演变。 公共卫生相关性：合作是一种基本的生物现象。例如，人体依赖于不同细胞类型之间的合作。疾病可以由破坏正常合作的骗子（如癌细胞）或通过形成不希望的合作（如在感染病毒或细菌中发现的合作）引起。发现和量化推动合作和作弊演变的机制的重要性，可能会揭示稳定或破坏合作的策略。

DESCRIPTION (Provided by the applicant) Abstract: Cooperation is wide-spread and has been postulated to drive major transitions in evolution. A cooperator pays a cost to benefit others, and when reciprocated, it gains a net benefit. However, Darwinian selection favors "cheaters" that consume benefits without paying a fair cost. Many cooperative systems have evolved sophisticated cheater recognition/exclusion mechanisms. How did cheater-resisting mechanisms evolve from simple cooperative systems? To address this question, I created a genetically tractable cooperative system that can be observed as it evolves, step-by-step, from its inception toward increased stability. It consists of two engineered non-mating yeast strains - a red-fluorescent R strain that requires adenine and releases lysine and a yellow-fluorescent Y strain that requires lysine and releases adenine. I observed that: the system is viable - able to grow from low-density to saturation in the absence of adenine and lysine supplements, over a wide range of conditions; system viability requirements could be calculated from growth, death, and metabolic properties of the two cooperating strains; the system evolved increased system viability: the minimum cell density required for system viability was reduced 100-fold. My group will: discover the diversity of changes that increase system viability. Pro-cooperation changes must act through benefiting self and/or partner. Properties of evolved strains will be measured and their relative contributions to enhanced cooperation will be quantified. determine mechanisms of cheater tolerance. After introducing a cheater that consumes but does not release metabolites, we will select for cooperator/cheater cocultures with increased cheater tolerance and delineate mechanisms. investigate the possibility of spatial structure stabilizing cooperation. We will compare viability requirements and cheater tolerance of the cooperative system in a well-mixed liquid culture (no spatial structure) with those on an agar pad (with spatial structure). We hope to quantitatively understand the evolution of cooperation and cheater tolerance. Public Health Relevance: Cooperation is a fundamental biological phenomenon. For instance, the human body relies on cooperation between different cell types. Diseases can be caused either by cheaters (such as cancer cells) that destroy normal cooperation or by formation of undesired cooperation (such as those found among infecting viruses or bacteria). Discovering and quantifying the importance of mechanisms that drive the evolution of cooperation and cheating may reveal strategies to stabilize or destabilize cooperation.