从基因组学到功能蛋白质组学的研究

人类基因组草图绘制的完成,标志着生命科学已实质性地跨入了后基因组时代,研究重心已从揭示生命的所有遗传信息转移到在分子整体水平对功能的研究[1]。这种转向表明目前已进入功能基因组学(functional genom ics)以及随之产生的功能蛋白质组学(functional proteomics)等新学科领域的研究。     

Structural genomics of microbes: an objective

A comparison of the genome sequences of more than 20 microorganisms reveals that a large fraction of the genes have unknown functions. Determining the structures of the proteins coded by these genes may provide additional key information in an effort to uncover the molecular functions of such proteins and new protein fold patterns. Using existing technology, it is possible to obtain a complete sequence complement and a near complete structural complement for a small microbial genome. Such information may provide a comprehensive view of a small organism, which, in turn, can serve as a platform for understanding more complex organisms.     

GOing from functional genomics to biological significance

The chicken genome is sequenced and this, together with microarray and other functional genomics technologies, makes post-genomic research possible in the chicken. At this time, however, such research is hindered by a lack of genomic structural and functional annotations. Bio-ontologies have been developed for different annotation requirements, as well as to facilitate data sharing and computational analysis, but these are not yet optimally utilized in the chicken. Here we discuss genomic annotation and bio-ontologies. We focus specifically on the Gene Ontology (GO), chicken GO annotations and how these can facilitate functional genomics in the chicken. The GO is the most developed and widely used bio-ontology. It is the de facto standard for functional annotation. Despite its critical importance in analyzing microarray and other functional genomics data, relatively few chicken gene products have any GO annotation. When these are available, the average quality of chicken gene products annotations (defined using evidence code weight and annotation depth) is much less than in mouse. Moreover, tools allowing chicken researchers to easily and rapidly use the GO are either lacking or hard to use. To address all of these problems we developed ChickGO and AgBase. Chicken GO annotations are provided by complementary work at MSU-AgBase and EBI-GOA. The GO tools pipeline at AgBase uses GO to derive functional and biological significance from microarray and other functional genomics data. Not only will improved genomic annotation and tools to use these annotations benefit the chicken research community but they will also facilitate research in other avian species and comparative genomics.     

Trends in large-scale mouse mutagenesis: from genetics to functional genomics

The primary goal of mouse mutagenesis programmes is to develop a fundamental research infrastructure for mammalian functional genomics and to produce human disease models. Many large-scale programmes have been ongoing since 1997; these culminated in the International Knockout Mouse Consortium (IKMC) in 2007 with the aim to establish knockout and conditional mouse strains for all mouse genes. This article traces the origins and rationale of these large-scale mouse mutagenesis programmes.     

Pathogen virulence of Phytophthora infestans: from gene to functional genomics

The oomycete, Phytophthora infestans, is one of the most important plant pathogens worldwide. Much of the pathogenic success of P. infestans, the potato late blight agent, relies on its ability to generate large amounts of sporangia from mycelia, which release zoospores that encyst and form infection structures. Until recently, little was known about the molecular basis of oomycete pathogenicity by the avirulence molecules that are perceived by host defenses. To understand the molecular mechanisms interplay in the pathogen and host interactions, knowledge of the genome structure was most important, which is available now after genome sequencing. The mechanism of biotrophic interaction between potato and P. infestans could be determined by understanding the effector biology of the pathogen, which is until now poorly understood. The recent availability of oomycete genome will help in understanding of the signal transduction pathways followed by apoplastic and cytoplasmic effectors for translocation into host cell. Finally based on genomics, novel strategies could be developed for effective management of the crop losses due to the late blight disease.     

Environmental genomics: exploring the unmined richness of microbes to degrade xenobiotics

Increasing pollution of water and soils by xenobiotic compounds has led in the last few decades to an acute need for understanding the impact of toxic compounds on microbial populations, the catabolic degradation pathways of xenobiotics and the set-up and improvement of bioremediation processes. Recent advances in molecular techniques, including high-throughput approaches such as microarrays and metagenomics, have opened up new perspectives and pointed towards new opportunities in pollution abatement and environmental management. Compared with traditional molecular techniques dependent on the isolation of pure cultures in the laboratory, microarrays and metagenomics allow specific environmental questions to be answered by exploring and using the phenomenal resources of uncultivable and uncharacterized micro-organisms. This paper reviews the current potential of microarrays and metagenomics to investigate the genetic diversity of environmentally relevant micro-organisms and identify new functional genes involved in the catabolism of xenobiotics.     

Approaches to functional genomics in filamentous fungi

The study of gene function in filamentous fungi is a field of research that has made great advances in very recent years. A number of transformation and gene manipulation strategies have been developed and applied to a diverse and rapidly expanding list of economically important filamentous fungi and oomycetes. With the significant number of fungal genomes now sequenced or being sequenced, functional genomics promises to uncover a great deal of new information in coming years. This review discusses recent advances that have been made in examining gene function in filamentous fungi and describes the advantages and limitations of the different approaches.     

From genotype to phenotype in bovine functional genomics

In past 5 years, the promise that came with genome sequencing has revolutionized the functional genomics research field at unprecedented manner. It would soon know what all known genes do, particularly genes involved in genetic improvement of animal health and increase food animal production. With the availability of full bovine genomic sequence, yet we still have a lot of daunting tasks on 'genotype-to-phenotype problem' particularly about the phenotypic variations and trying to predict what genes are likely to be involved, and improved integrated interactive database. This article outlined and discussed about the current status of bovine functional genomics, recent development in bovine genome databases particularly in annotation of bovine genome, bovine quantitative trait loci database and its potential impact to unveil the from genotype-to-phenotype problem.     

Human obesity: toward functional genomics

Genetic and environmental aspects are recognized in the obesity field and attempts to elucidate multiple genes and gene/environment interactions are necessary. In rare cases of monogenic obesities, genetic tools have proved extremely powerful for identifying the genes responsible and for defining new syndromes. Abnormalities of genes involved in the leptin/melanocortin axis have been described. In common obesity, most studies include the search for genotype/phenotype associations without taking into account the influence of environment (diet, sedentary lifestyle) in the relationship. Many genes and candidate regions have been proposed to be involved in the determinism of human obesity. Among the limitations to this integrated approach, one can cite the difficulty of having large enough samples as well as biocomputing tools that are still in their infancy for accessing the question of multiple interactions with no "a priori hypotheses". This picture will probably change rapidly in the future. The purpose of this paper is to present some examples of the knowledge acquired in the field of obesity genetics and the new ongoing tools and developments that aim at studying the contribution of genes to obesity and their response to environmental changes. The capacity for studying multiple genes at once at the DNA or RNA levels is rapidly growing. Finally, tremendous progress in biocomputing will allow the integration of information from different sources (i.e. environment, phenotype, genotype, gene expression) and thus improve our ability to deal with complexity. Examples of these approaches exist in humans and in animal models.     

蚜虫基因组及功能基因组研究进展

蚜虫作为刺吸式昆虫和植物病毒的传播者,已经成为严重威胁农业生产发展的重要害虫之一。近几年随着分子生物学的发展,尤其是基因组测序技术的进步,蚜虫基因组学和功能基因组学取得了重大突破,使我们对蚜虫特殊的生物学特征有了深层次的认识。本文就蚜虫与内共生菌关系、表型可塑性、发育和生殖、系统进化、解毒酶基因家族以及唾液腺方面在基因组和功能基因组水平上的研究进展进行了综述。