Blended Inheritance As a Genetic Consequence of Unlimited Regeneration

描述(由申请人提供)：解开遗传学法则的世纪和发育调控的分子本质是由主力模型的灵感选择所实现的：从大肠杆菌到家养分枝杆菌。他们都遵守孟德尔式的遗传规则，使其中的基因分析合乎逻辑和直截了当。由于繁殖过程中的单细胞瓶颈，构成这些生物体的细胞的生殖利益是一致的。这些原理对癌细胞不起作用，因为癌细胞积累了促进繁殖的突变。这些细胞“有兴趣”以牺牲其他非癌细胞为代价进行复制，从而损害“宿主生物体”。这一场景说明了多人社区之间的典型“冲突”--无论是异质HIV病毒在患者体内繁殖、缩短他们的寿命，还是员工通过争取更高的工资来损害公司的竞争能力。行星动物是分析再生的一个流行模型。在未来，再生将使人类健康取得巨大进步。必然地，再生将导致一个由异质细胞基因组组成的有机体。正如供体组织排斥反应一直是移植医学中的一个问题一样，当再生技术变得先进时，一个问题将是细胞之间缺乏沟通和合作。传统的遗传模型不足以破译生物体内冲突和细胞错误沟通的规则，但浮游生物却可以。它们通常要么是有性生殖，要么是孤雌生殖--这两个过程都涉及减数分裂和基因组瓶颈。然而，当一个浮游生物谱系遇到一个取消减数分裂的突变时，它仍然可以快乐地生存下来。这要归功于爬行动物无限的再生能力。在任何轴向上都可以切开，所有缺失的成人解剖特征都会完全再生。在20世纪70年代，发现了具有减数分裂危害突变的三角涡虫种群。这些种群完全通过分裂进行繁殖。2010年，来自这些意大利种群的额外的浮游生物样本被保护起来，并被带到了PI的实验室。它们仍然通过横向分裂和随后的再生进行显性繁殖。它们必须代表“基因组被”，即个体由多种遗传异质的细胞群体类型组成。他们拥有多少个体内的遗传变异？在多能细胞迁移和分化的过程中，行星动物如何解决细胞间的生殖冲突？行星动物如何协调遗传异质细胞之间的沟通和协调问题？对个体基因组进行深度测序，对分化过程中的个体多能细胞进行信使核糖核酸测序，以及近似贝叶斯计算将被用于回答这些和其他问题。摩根在遗传学方面的第一次实验是在行星动物身上进行的，但他转向了一个更简单的苍蝇模型来描述孟德尔遗传规律。现在是回到混合遗传模式的时候了，在这种模式下，数十万个基因组被代代相传。

DESCRIPTION (provided by applicant): The Century of untangling the laws of Genetics, and molecular nature of developmental regulation was enabled by inspired choice of workhorse models: from E. coli to M. domesticus. All of them abide to the rules of Mendelian inheritance, making the genetic analyses in them logical and straightforward. The reproductive interests of cells constituting these organisms are aligned due to a single cell bottleneck during reproduction. These principles do not work for cancer cells, which have accumulated mutations promoting reproduction. These cells are 'interested' in reproducing at the expense of other non-cancer cells, thereby harming the 'host organism'. This scenario illustrates a typical 'conflict' between multi-player communities - be it heterogeneous HIV viruses multiplying within a patient, shortening their lifespan, or employees hurting the competitive ability of a company by striking for a greater salary. Planarians are a popular model for the analyses of regeneration. Regeneration will, in the future, enable dramatic advances in human health. By necessity, regeneration will result in an organism consisting of heterogeneous genomes of cells. Just as donor-tissue rejection has been a problem in transplant medicine, when regeneration technologies become advanced, a problem will be in the lack of communication and cooperation between cells. Traditional genetic models are inadequate for deciphering the rules of intraorganismal conflicts and cell mis-communication, but planarians are. They are typically either sexual or parthenogenetic - both processes involving meiosis and a genome bottleneck. However, when a planarian lineage encounters a mutation abolishing meiosis, it can still happily survive. This is due to the planarian unrestricted regenerative ability. Planarians can be cut in any axial orientation and complete regeneration of all absent adult anatomical features occurs. In the 1970s, Dugesia gonocephala planarian populations that are fixed for meiosis-compromising mutations were discovered. These populations reproduce exclusively by fission. Additional samples of planarians from these Italian populations were secured and brought to the PI's lab in 2010. They still reproduce explicitly by transverse fission with subsequent regeneration. They must represent 'genomic quilts', where individuals are made of multiple genetically heterogeneous cell population types. How much intraindividual genetic variation do they possess? How do planarians resolve reproductive conflicts among cells in the process of pluripotent cell migration and differentiation? How do planarians mediate communication and coordination problems between genetically heterogeneous cells? Deep sequencing of individuals genomes, mRNA sequencing of individual pluripotent cells in the process of differentiation, and approximate Bayesian computations will be used to answer these and other questions. Morgan's first experiments in Genetics were with planarians, but he switched to a simpler fly model to describe the laws of Mendelian inheritance. It is time now to come back to the model of blended inheritance, in which hundreds of thousands of genomes are transmitted from generation to generation.