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）：该项目主要涉及经验分析，以更好地了解影响果蝇，加密环球和人乳头虫病毒的同义密码子使用的力。果蝇项目的目的是（1）推断自然选择对单个氨基酸的密码子使用的作用；（2）推断自然部分沿基因长度的密码子使用的差异作用；（3）估算同义突变的选择系数。第二个目的是对分析的后续措施，该分析表明范围内的基因组首选密码子峰值峰值大约是从开始密码子下游的一百个密码子。选择的推论将基于DNA序列多态性和差异的水平和模式。目前正在针对四种果蝇Simulans菌株，五个D.毛丽蒂亚菌菌株和1个sechellia菌株生成20个蛋白质编码基因的数据集，该数据集已从开始到终止密码子进行测序。基于观察到的DNA序列变化水平，将至少添加25个基因，以提供足够的统计能力来解决目标。加密球项目的目的是测试首选密码子使用的假设反映了对基因产物有效表达的选择。加密赛是一种单细胞真菌和机会性人类病原体，具有185种剪接基因。其中有19个被选为研究的合适候选者，这将比较替代转录本的表达与每个转录本独特的区域的密码子偏置。可以预测，表达将与首选密码子的使用呈正相关，这些密码子已通过多元统计分析推断出来。表达将通过定量实时PCR测量，并通过克隆和分子分析CDNA来确认。该项目完成后，将对果蝇的相关项目进行试验。人乳头瘤病毒项目的目的是确认初步发现，这些病毒的基因组在基础组成和密码子使用方面不足。初步数据表明，人类乳头瘤病毒是人类感染病毒的最贫困的人，正在增加其G+C含量。这可能表明适应人类基因组，G和C比HPV更丰富。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，并将导致新的分析方法。此外，还将研究两个特别关注的生物体：机会性病原体新形象体和人乳头瘤病毒。

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。