基因组水平的基因进化分析与水平转移基因的识别
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摘要
随着人类基因组计划的完成和后基因组时代的到来,生物序列数据呈指数级增长,分析处理大批量数据,从中提取有价值的信息,成为生物信息研究中的首要任务。本文利用生物信息学方法在基因组水平对B7-H3基因进行了鉴定,探索B7-H3基因的进化过程;分析了杆状病毒基因组的遗传进化模式,并对其水平转移基因进行了识别研究。
1.基因组水平上对B7-H3基因进行鉴定及系统发育分析
B7-H3基因一个免疫共刺激分子,属于B7蛋白家族,分子中含一个IgV和一个IgC结构域。通过多重PCR,小鼠B7-H3基因中发现有一个胞外的IgV-IgC结构域(2IgB7-H3),而人的B7-H3基因中出现一个剪接变体,含有串联重复的IgV-IgC-IgV-IgC结构域(4IgB7-H3)。对仓鼠B7-H3基因进行结构预测,显示为2IgB7-H3,猴B7-H3基因的分析表明它的结构与人类基因相似。为了探索B7-H3基因的进化过程,基于现有的基因组序列对B7-H3进行了基因组水平上的结构和系统发育分析。17个哺乳动物的B7-H3基因被预测出有串联重复的4Ig结构域。通过对这些4IgB7-H3基因的结构与进化分析,得出这些基因产生的原因是结构域的复制。此外,2Ig和4Ig这两种结构亚型之间没有表现出功能的差异。这可能是发生在4IgB7-H3中的结构域复制事件导致了功能上的冗余。
2.家蚕核型多角体病毒水平转移基因分析
为了探讨杆状病毒基因组的遗传进化模式,利用家蚕核型多角体病毒(Bombyx mori nuclearpolyhedrosisvirus, BmNPV)和其宿主家蚕全基因组数据,进行了全基因组的同源性搜索和系统进化分析,结果显示,BmNPV的几丁质酶基因、凋亡抑制蛋白3基因和尿苷二磷酸葡萄糖转移酶基因为水平转移基因。这3个基因都来源于其宿主昆虫。通过核苷酸组成、密码子偏好性、选择压力等基因特征分析,发现BmNPV水平转移基因与其基因组序列存在明显差异,进一步验证水平转移基因的外源性。对3个水平转移基因的功能分析发现它们有利于杆状病毒在宿主昆虫中的侵染与繁殖,并提高杆状病毒在昆虫中的生存能力。
Currently, available biologic sequence data are increasing exponentially with the completion of human genomic project (HGP) and the coming of the post genome era. It becomes a very important task in the study of bioinformatics to analyze huge dataset and obtain the valuable information. In this study, we described the application of two different levels by methods of bioinformatics.
1. Genome-wide identification and evolutionary analysis of B7-H3
B7-H3 is an immune costimulatory molecule of the B7 family that contains a set of immunoglobulin-V (IgV) and immunoglobulin-C (IgC) domains. By multiplex PCR, mouse B7-H3 was found to have an extracellular IgV-IgC domain (2IgB7-H3), whereas the dominantly expressed form of human B7-H3 was found to be a splice variant containing tandemly duplicated IgV-IgC-IgV-IgC domains (4IgB7-H3). Hamster B7-H3 was predicted to be 2IgB7-H3, and the monkey B7-H3 gene was predicted to have a similar structure to the human gene. To explore the evolutionary process of B7-H3 gene, we conducted a genome-wide structure and phylogenetic analysis of B7-H3 genes in currently sequenced genomes. Based on the available data, seventeen mammalian B7-H3 genes were predicted to have tandemly duplicated 4Ig domains. The analysis of gene structure and phylogenesis reveal that these 4IgB7-H3 genes resulted from domain duplication. Nevertheless, no difference in function has been observed between the two isoforms. It is likely that domain duplication in 4IgB7-H3 leads to functional redundancy.
2. Analysis of Horizontal Transfer Gene of Bombyx mori NPV
For research on genetic characters and evolutionary origin of the genome of baculoviruses, three horizontally transferred genes were identified using the Blast search and phylogentic analysis method with Bombyx mori NPV and Bombyx mori genomic databases. These genes were origined from host insects, and the detected transferred directions are the HGT from insects to baculoviruses. The analysis results showed that baculovirus had obtained IAP and UGT gene through transfer of the transposon. There are lots of differences between the features of horizontal transferred genes and the ones of whole genomic genes, such as nucleotide composition, codon usagebias and selection pressure. These results reconfirm that the horizontally transferred genes are exogenous. Interestingly, these genes are all known tobe directly involved in the infection of insect hosts by baculoviruses. These findings suggested that horizontally transferred genes accuired from an ancestral host insect can control host physiology and increase the efficiency of baculoviruse transmission.
1.基因组水平上对B7-H3基因进行鉴定及系统发育分析
B7-H3基因一个免疫共刺激分子,属于B7蛋白家族,分子中含一个IgV和一个IgC结构域。通过多重PCR,小鼠B7-H3基因中发现有一个胞外的IgV-IgC结构域(2IgB7-H3),而人的B7-H3基因中出现一个剪接变体,含有串联重复的IgV-IgC-IgV-IgC结构域(4IgB7-H3)。对仓鼠B7-H3基因进行结构预测,显示为2IgB7-H3,猴B7-H3基因的分析表明它的结构与人类基因相似。为了探索B7-H3基因的进化过程,基于现有的基因组序列对B7-H3进行了基因组水平上的结构和系统发育分析。17个哺乳动物的B7-H3基因被预测出有串联重复的4Ig结构域。通过对这些4IgB7-H3基因的结构与进化分析,得出这些基因产生的原因是结构域的复制。此外,2Ig和4Ig这两种结构亚型之间没有表现出功能的差异。这可能是发生在4IgB7-H3中的结构域复制事件导致了功能上的冗余。
2.家蚕核型多角体病毒水平转移基因分析
为了探讨杆状病毒基因组的遗传进化模式,利用家蚕核型多角体病毒(Bombyx mori nuclearpolyhedrosisvirus, BmNPV)和其宿主家蚕全基因组数据,进行了全基因组的同源性搜索和系统进化分析,结果显示,BmNPV的几丁质酶基因、凋亡抑制蛋白3基因和尿苷二磷酸葡萄糖转移酶基因为水平转移基因。这3个基因都来源于其宿主昆虫。通过核苷酸组成、密码子偏好性、选择压力等基因特征分析,发现BmNPV水平转移基因与其基因组序列存在明显差异,进一步验证水平转移基因的外源性。对3个水平转移基因的功能分析发现它们有利于杆状病毒在宿主昆虫中的侵染与繁殖,并提高杆状病毒在昆虫中的生存能力。
Currently, available biologic sequence data are increasing exponentially with the completion of human genomic project (HGP) and the coming of the post genome era. It becomes a very important task in the study of bioinformatics to analyze huge dataset and obtain the valuable information. In this study, we described the application of two different levels by methods of bioinformatics.
1. Genome-wide identification and evolutionary analysis of B7-H3
B7-H3 is an immune costimulatory molecule of the B7 family that contains a set of immunoglobulin-V (IgV) and immunoglobulin-C (IgC) domains. By multiplex PCR, mouse B7-H3 was found to have an extracellular IgV-IgC domain (2IgB7-H3), whereas the dominantly expressed form of human B7-H3 was found to be a splice variant containing tandemly duplicated IgV-IgC-IgV-IgC domains (4IgB7-H3). Hamster B7-H3 was predicted to be 2IgB7-H3, and the monkey B7-H3 gene was predicted to have a similar structure to the human gene. To explore the evolutionary process of B7-H3 gene, we conducted a genome-wide structure and phylogenetic analysis of B7-H3 genes in currently sequenced genomes. Based on the available data, seventeen mammalian B7-H3 genes were predicted to have tandemly duplicated 4Ig domains. The analysis of gene structure and phylogenesis reveal that these 4IgB7-H3 genes resulted from domain duplication. Nevertheless, no difference in function has been observed between the two isoforms. It is likely that domain duplication in 4IgB7-H3 leads to functional redundancy.
2. Analysis of Horizontal Transfer Gene of Bombyx mori NPV
For research on genetic characters and evolutionary origin of the genome of baculoviruses, three horizontally transferred genes were identified using the Blast search and phylogentic analysis method with Bombyx mori NPV and Bombyx mori genomic databases. These genes were origined from host insects, and the detected transferred directions are the HGT from insects to baculoviruses. The analysis results showed that baculovirus had obtained IAP and UGT gene through transfer of the transposon. There are lots of differences between the features of horizontal transferred genes and the ones of whole genomic genes, such as nucleotide composition, codon usagebias and selection pressure. These results reconfirm that the horizontally transferred genes are exogenous. Interestingly, these genes are all known tobe directly involved in the infection of insect hosts by baculoviruses. These findings suggested that horizontally transferred genes accuired from an ancestral host insect can control host physiology and increase the efficiency of baculoviruse transmission.
引文
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