Empirical analysis of natural selection on codon usage in eukaryotes

真核生物密码子使用自然选择的实证分析

基本信息

批准号：
7304667
负责人：
RICHARD M KLIMAN
金额：
$ 19.58万
依托单位：
CEDAR CREST COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-30 至 2011-09-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7304667
关键词：
Address Affinity Amino Acids Anticodon Attention Base Composition Binding Cells Class Code Codon Nucleotides Collection Complex Condition Cryptococcus Cryptococcus neoformans DNA Sequence DNA biosynthesis Data Data Set Drosophila genus Effectiveness Engineering Equilibrium Etiology Eukaryota Eukaryotic Cell Evolution Gene Expression Genes Genetic Genetic Code Genetic Polymorphism Genome Goals Guanine + Cytosine Composition Health Horizontal Gene Transfer Human Human Genome Human Papillomavirus Individual Initiator Codon Introns Lead Length Literature Measures Messenger RNA Molecular Molecular Analysis Molecular Cloning Mutation Natural Selections Numbers Open Reading Frames Organism Pattern Polymerase Chain Reaction Population Population Sizes Positioning Attribute Process Progress Reports Proteins Public Health Rate Relative (related person)Research Research Personnel Signal Transduction Spliced Genes Study models Terminator Codon Testing Thinking Time Transcript Transfer RNA Transgenes Translations Variant Virus analytical method base cost follow-up fungus genome sequencing insight interest pathogen preference trend

项目摘要

DESCRIPTION (provided by applicant): This project primarily involves empirical analyses to better understand the forces that influence synonymous codon usage in Drosophila, Cryptococcus and human papillomaviruses. The aims of the Drosophila project are (1) to infer the action of natural selection on codon usage of individual amino acids; (2) to infer the differential action of natural section on codon usage along the length of genes; and (3) to estimate selection coefficients for synonymous mutations. The second aim is a follow-up to analyses that indicated a genome-wide preferred codon usage peak approximately one hundred codons downstream from the start codon. Inference of selection will be based on levels and patterns of DNA sequence polymorphism and divergence. A data set of twenty protein-coding genes, sequenced from start through stop codon, is currently being generated for four strains of Drosophila simulans, five strains of D. mauritiana and one strain of D. sechellia. Based on observed levels of DNA sequence variation, another twenty five genes, at a minimum, will be added to this data set to provide sufficient statistical power to address the aims. The aim of the Cryptococcus project is to test the hypothesis that preferred codon usage reflects selection for efficient expression of gene products. Cryptococcus, a single-celled fungus and an opportunistic human pathogen, has 185 alternatively spliced genes. Nineteen of these have been chosen as suitable candidates for the study, which will compare expression of alternative transcripts with the codon bias of the regions unique to each transcript. It is predicted that expression will correlate positively with the usage of preferred codons, which have been inferred by multivariate statistical analysis. Expression will be measured by quantitative real-time PCR, and confirmed by cloning and molecular analysis of cDNAs. Once this project is completed, a related project on Drosophila will be piloted. The aim of the human papillomavirus project is to confirm a preliminary finding that the genomes of these viruses are not at equilibrium with respect to base composition and codon usage. Preliminary data indicate that human papillomaviruses, among the most GC-poor of the human-infecting viruses, are in the process of increasing their G+C contents. This may indicate adaptation to the human genome, which is much richer in G and C than HPVs. Analysis of human-infecting viruses also provides insight into the human DNA replication and gene expression machinery, on which HPVs rely. This project addresses population and evolutionary genetics questions and will lead to new analytical methods. Additionally, two organisms of special concern to human health will be studied: the opportunistic pathogen Cryptococcus neoformans and human papillomaviruses.

描述（由申请人提供）：该项目主要涉及实证分析，以更好地了解影响果蝇、隐球菌和人乳头瘤病毒中同义密码子使用的力量。果蝇项目的目标是（1）推断自然选择对单个氨基酸密码子使用的作用； (2) 推断自然切片对沿基因长度的密码子使用的差异作用； (3)估计同义突变的选择系数。第二个目标是后续分析，表明全基因组首选密码子使用峰值位于起始密码子下游大约一百个密码子。选择的推断将基于 DNA 序列多态性和分歧的水平和模式。目前正在为 4 个模拟果蝇菌株、5 个 D. mauritiana 菌株和一个 D. sechellia 菌株生成一个由 20 个蛋白质编码基因组成的数据集，从起始密码子到终止密码子进行测序。根据观察到的 DNA 序列变异水平，至少另外 25 个基因将被添加到该数据集中，以提供足够的统计能力来实现目标。隐球菌项目的目的是检验以下假设：首选密码子使用反映了对基因产物有效表达的选择。隐球菌是一种单细胞真菌，也是一种机会性人类病原体，具有 185 个选择性剪接基因。其中十九个已被选为该研究的合适候选者，该研究将比较替代转录本的表达与每个转录本独特区域的密码子偏差。据预测，表达将与首选密码子的使用呈正相关，这是通过多变量统计分析推断的。表达将通过定量实时 PCR 进行测量，并通过 cDNA 的克隆和分子分析进行确认。该项目完成后，将在果蝇上试点相关项目。人乳头瘤病毒项目的目的是证实初步发现，即这些病毒的基因组在碱基组成和密码子使用方面不平衡。初步数据表明，人乳头瘤病毒是人类感染病毒中 GC 最缺乏的病毒之一，其 G+C 含量正在增加。这可能表明对人类基因组的适应，人类基因组的 G 和 C 含量比 HPV 丰富得多。对人类感染病毒的分析还可以深入了解 HPV 所依赖的人类 DNA 复制和基因表达机制。该项目解决了人口和进化遗传学问题，并将带来新的分析方法。此外，还将研究对人类健康特别重要的两种生物：机会病原体新型隐球菌和人乳头瘤病毒。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A new test for selection applied to codon usage in Drosophila simulans and D. mauritiana.

一种新的选择测试适用于模拟果蝇和毛里求斯果蝇的密码子使用。

DOI：
10.1007/s00239-008-9072-x
发表时间：
2008
期刊：
Journal of molecular evolution
影响因子：
3.9
作者：
Llopart,Ana;Mabillé,Aelén;Peters-Hall,JenniferR;Comeron,JosepM;Kliman,RichardM
通讯作者：
Kliman,RichardM

Interactions between natural selection, recombination and gene density in the genes of Drosophila.

果蝇基因中自然选择、重组和基因密度之间的相互作用。