Deciphering the mechanisms and dynamics of proto-gene evolution

破译原基因进化的机制和动力学

• 批准号: 9460085
• 负责人: Anne-Ruxandra Carvunis
• 金额: $ 24.9万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9460085
• 关键词: Algorithms; Award; Biological Process; Birth; Cells; Clustered Regularly Interspaced Short Palindromic Repeats; Collection; Complex; Evolution; Fission Yeast; Frequencies; Gene Duplication; Genes; Genetic; Genetic Transcription; Genetic Variation; Genome; Genomics; Human; Insecta; Junk DNA; Laboratories; Lead; Learning; Malaria; Mammals; Methods; Modeling; Molecular; Mutation; Natural History; Natural Selections; Nature; Open Reading Frames; Organism; Prevalence; Process; Proteins; Public Health; Race; Research; Risk; Rodent; Saccharomyces cerevisiae; Structure; Synteny; Testing; Training; Transcript; Translating; Translations; Virulent; Work; Yeasts; arm; cancer cell; design; duplicate genes; experimental study; fitness; functional genomics; fungus; killings; mutant; novel; overexpression; pathogen; polypeptide; predictive modeling; pressure; promoter; reconstruction; synthetic biology; vector control

The phenomenon of de novo gene birth may underlie what makes each species unique, yet it remains poorly understood. We have recently found evidence that regions of the genome thought to be junk DNA can be translated, providing an evolutionary reservoir of “proto-genes” that promote de novo gene birth. This proposal aims at characterizing the mechanisms and dynamics of proto-gene evolution by investigating three complementary angles: 1) How do proto-genes promote adaptation? To answer this question, we will overexpress proto-genes and assorted control sequences in yeast and dissect their impact on cellular fitness across multiple environmental conditions. 2) Is the proto-gene model universal? To answer this question, we will perform a computational reconstruction of the natural history of de novo gene birth in mammals, insects, malaria and fungi though the design and implementation of novel dating algorithms. This will enable us to evaluate which features that characterize these distinct lineages, such as genome size for example, influence the frequency of proto-gene evolution. 2) How do genomic sequences exit the non-genic state? It is unclear whether a proto-gene is more likely to emerge from a non-genic sequence following mutations emulating a novel promoter structure, or an open reading frame. To assess the feasibility of these competing mechanisms, we will construct yeast mutants where a gene has been synthetically killed by destroying either is open reading frame or its promoter. We will then evolve these mutants under a variety of selective pressures and observe if one mechanism is more successful than the other.

从头基因诞生的现象可能是每个物种独特之处的基础，但人们对它的了解仍然很少。 我们最近发现的证据表明，基因组中被认为是垃圾DNA的区域可以被翻译，这提供了一个新的证据。 进化的“原基因”的水库，促进从头基因诞生。该提案旨在描述 原基因进化的机制和动力学，通过研究三个互补的角度： 1)原始基因如何促进适应？为了回答这个问题，我们将过度表达原基因， 酵母中的控制序列，并剖析它们在多种环境条件下对细胞适应性的影响。 2)原始基因模型是否具有普遍性？为了回答这个问题，我们将执行计算重建的 哺乳动物、昆虫、疟疾和真菌的从头基因诞生的自然历史， 新颖的约会算法这将使我们能够评估哪些特征表征这些不同的谱系，例如， 例如，基因组的大小会影响原基因进化的频率。 2)基因组序列如何退出非基因状态？目前还不清楚一个原始基因是否更有可能出现在 模拟新启动子结构的突变后的非基因序列，或开放阅读框。评估 这些竞争机制的可行性，我们将构建酵母突变体，其中一个基因已被合成 通过破坏开放阅读框架或其启动子而被杀死。然后我们将在各种条件下进化这些突变体， 选择性压力，并观察一种机制是否比另一种机制更成功。