Elucidating the evolutionary mode of binding site gain at novel loci

阐明新位点结合位点获得的进化模式

• 批准号: 8706190
• 负责人: Christopher Eugene Ellison
• 金额: $ 5.51万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-20 至 2015-08-19
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8706190
• 关键词: Acetylation; Affinity; Alleles; Anemia; Binding; Binding Sites; ChIP-seq; Chromosomes; Chromosomes, Human, Pair 1; Code; Complex; DNA Sequence; DNA Transposable Elements; Data; Diagnosis; Disease; Dosage Compensation (Genetics); Drosophila genus; Elements; Evolution; Frequencies; Gene Expression; Gene Expression Regulation; Genes; Genetic Polymorphism; Genetic Transcription; Genome; Genomics; Histone H4; Link; Location; Lysine; Malignant Neoplasms; Phylogenetic Analysis; Play; Process; Proteins; Reading; Recruitment Activity; Relative (related person); Research Project Grants; Resolution; Ribonucleoproteins; Role; Sensitivity and Specificity; Series; Sex Chromosomes; Signal Transduction; Sister; Site; Source; System; Transcriptional Regulation; Up-Regulation; Work; X Chromosome; Y Chromosome; autosome; base; cancer type; fitness; human disease; improved; male; novel; pyrosequencing; research study; sex; trait; transcription factor

DESCRIPTION (provided by applicant): Genomic changes that influence gene expression can have significant impacts on the evolution of novel morphological traits and play important roles in diseases such as cancer. While much effort has been dedicated towards defining networks of co-regulated genes, comparatively little is known about the relative importance of processes that result in the recruitment of gene expression regulators to novel and previously unbound locations within the genome. The neo-X chromosome of Drosophila miranda represents an ideal system for studying such processes. This chromosome is young (~1 MYA) yet is already capable of recruiting a regulatory complex which up-regulates gene expression levels across the entire male X chromosome by a factor of two. This process is known as dosage compensation and occurs specifically in males to compensate for their missing X chromosome (e.g. XY versus XX). Genome assemblies from close relatives of D. miranda will be used to identify the mutational path leading to the evolution of the dosage compensation complex binding sites on the neo-X chromosome. From this analysis, it will be possible to determine the relative importance of the various mechanisms by which a binding motif evolves at a novel location in the genome, including de novo evolution from a pre-site or random sequence, transpositions from other genomic locations, or the local amplification of weak binding sites. In addition, polymorphism data from wild D. miranda lines will be analyzed to determine if these binding sites evolved under positive selection, which has implications for the process of Y chromosome degeneration.

描述（由申请人提供）：影响基因表达的基因组变化可以对新的形态特征的进化产生重大影响，并在癌症等疾病中发挥重要作用。虽然很多努力都致力于定义共调控基因的网络，但相对而言，人们对导致基因表达调控因子招募到基因组中新的和先前未结合的位置的过程的相对重要性知之甚少。米兰达果蝇的新x染色体代表了研究这一过程的理想系统。这条染色体是年轻的（约1 MYA），但已经能够招募一个调节复合体，以两倍的倍数上调整个男性X染色体的基因表达水平。这个过程被称为剂量补偿，特别发生在男性身上，以补偿他们缺失的X染色体（例如XY对XX）。来自D. miranda近亲属的基因组组装将用于鉴定导致新x染色体上剂量补偿复合物结合位点进化的突变途径。通过这一分析，将有可能确定结合基序在基因组新位置进化的各种机制的相对重要性，包括从预位点或随机序列从头进化，来自其他基因组位置的转位，或弱结合位点的局部扩增。此外，将分析野生D. miranda系的多态性数据，以确定这些结合位点是否在正选择下进化，这对Y染色体变性过程具有重要意义。