Mycobacterium du jour: what's on tomorrow's menu?

Tremendous resources are being directed towards fundamental and applied research on Mycobacterium tuberculosis. Concurrently, diseases caused by other, non-tuberculous mycobacteria (NTM), are on the rise in many settings. For many of these 'atypical mycobacteria', there is no genome sequence data and a limited understanding of their biology. Consequently, they are often felt to be 'ubiquitous' in the environment and that disease occurs largely independent of bacterial factors, in an immunocompromised host. As the distribution of these organisms in human and environmental samples is decidedly non-random, there is indirect evidence that exposure, infection and disease due to these organisms are in part determined by bacterial factors. Knowledge on how different mycobacterial species engage the host differently will help provide predictive information on the epidemiology and biology of infection with these organisms. Already, post-genomic study of M. avium has pointed to the existence of variable genomic regions that likely represent mycobacterial pathogenicity islands. An additional benefit of further genomic study of NTM will be the provision of an out-group to better appreciate M. tuberculosis, potentially explaining the sequence of genomic events that originally permitted an environmental mycobacterium to evolve into a host-associated pathogen.     

Genome sequence of Cronobacter sakazakii E899, a strain associated with human illness

Cronobacter has caused numerous illnesses in neonates, infants, and children. Here we report the draft genome of Cronobacter sakazakii E899. Whole-genome sequence analysis of Cronobacter strains provides a tool for understanding the genomic regions specific to each individual species.     

Genome-Wide Association Study Identifies Loci Associated with Resistance to Viral Nervous Necrosis Disease in Asian Seabass

Viral nervous necrosis disease (VNN), caused by nervous necrosis virus (NNV), is one major threat to mariculture. Identifying loci and understanding the mechanisms associated with resistance to VNN are important in selective breeding programs. We performed a genome-wide association study (GWAS) using genotyping-by-sequencing (GBS) to study the genomic architecture of resistance to NNV infection in Asian seabass. We genotyped 986 individuals from 43 families produced by 15 founders with 44498 bi-allelic genetic variants using GBS. The GWAS identified three genome-wide significant loci on chromosomes 16, 19, and 20, respectively, and six suggestive loci on chromosomes 1, 8, 14, 15, 21, and 24, respectively, associated with resistance to NNV infection measured as binary and quantitative traits. Using the 500 most significant markers in combination with a training population of 800 samples could reach a genomic prediction accuracy of 0.7. Candidate genes significantly associated with resistance to NNV, including lysine-specific demethylase 2A, beta-defensin 1, and cystatin-B, which play important roles in immune responses against virus infection, were identified. Almost all the candidate genes were differentially expressed in different tissues against NNV infection. The significant genetic variants can be used in genomic selection and help understand the mechanism of resistance to VNN. Future studies should use populations of large effective size and whole genome resequencing to identify more useful genetic variants.     

Genomes, free radicals and plant cell invasion: recent developments in plant pathogenic fungi

This review describes current advances in our understanding of fungal-plant interactions. The widespread application of whole genome sequencing to a diverse range of fungal species has allowed new insight into the evolution of fungal pathogenesis and the definition of the gene inventories associated with important plant pathogens. This has also led to functional genomic approaches to carry out large-scale gene functional analysis. There has also been significant progress in understanding appressorium-mediated plant infection by fungi and its underlying genetic basis. The nature of biotrophic proliferation of fungal pathogens in host tissue has recently revealed new potential mechanisms for cell-to-cell movement by invading pathogens.     

Importance of genetic drift during Pleistocene divergence as revealed by analyses of genomic variation

Determining what factors affect the structuring of genetic variation is key to deciphering the relative roles of different evolutionary processes in species differentiation. Such information is especially critical to understanding how the frequent shifts and fragmentation of species distributions during the Pleistocene translates into species differences, and why the effect of such rapid climate change on patterns of species diversity varies among taxa. Studies of mitochondrial DNA (mtDNA) have detected significant population structure in many species, including those directly impacted by the glacial cycles. Yet, understanding the ultimate consequence of such structure, as it relates to how species divergence occurs, requires demonstration that such patterns are also shared with genomic patterns of differentiation. Here we present analyses of amplified fragment length polymorphisms (AFLPs) in the montane grasshopper Melanoplus oregonensis to assess the evolutionary significance of past demographic events and associated drift-induced divergence as inferred from mtDNA. As an inhabitant of the sky islands of the northern Rocky Mountains, this species was subject to repeated and frequent shifts in species distribution in response to the many glacial cycles. Nevertheless, significant genetic structuring of M. oregonensis is evident at two different geographic and temporal scales: recent divergence associated with the recolonization of the montane meadows in individual sky islands, as well as older divergence associated with displacements into regional glacial refugia. The genomic analyses indicate that drift-induced divergence, despite the lack of long-standing geographic barriers, has significantly contributed to species divergence during the Pleistocene. Moreover, the finding that divergence associated with past demographic events involves the repartitioning of ancestral variation without significant reductions of genomic diversity has intriguing implications - namely, the further amplification of drift-induced divergence by selection.     

Universal Pattern and Diverse Strengths of Successive Synonymous Codon Bias in Three Domains of Life, Particularly Among Prokaryotic Genomes

There has been significant progress in understanding the process of protein translation in recent years. One of the best examples is the discovery of usage bias in successive synonymous codons and its role in eukaryotic translation efficiency. We observed here a similar type of bias in the other two life domains, bacteria and archaea, although the bias strength was much smaller than in eukaryotes. Among 136 prokaryotic genomes, 98 were found to have significant bias from random use of successive synonymous codons with Z scores larger than three. Furthermore, significantly different bias strengths were found between prokaryotes grouped by various genomic or biochemical characteristics. Interestingly, the bias strength measured by a general Z score could be fitted well (R = 0.83, P < 10⁻¹⁵) by three genomic variables: genome size, G + C content, and tRNA gene number based on multiple linear regression. A different distribution of synonymous codon pairs between protein-coding genes and intergenic sequences suggests that bias is caused by translation selection. The present results indicate that protein translation is tuned by codon (pair) usage, and the intensity of the regulation is associated with genome size, tRNA gene number, and G + C content.     

A biological network in Saccharomyces cerevisiae prevents the deleterious effects of endogenous oxidative DNA damage

In this study, we used Saccharomyces cerevisiae to identify a biological network that prevents the deleterious effects of endogenous reactive oxygen species. The absence of Tsa1, a key peroxiredoxin, caused increased rates of mutations, chromosomal rearrangements, and recombination. Defects in recombinational DNA double strand break repair, Rad6-mediated postreplicative repair, and DNA damage and replication checkpoints caused growth defects or lethality in the absence of Tsa1. In addition, the mutator phenotypes caused by a tsa1 mutation were significantly aggravated by defects in Ogg1, mismatch repair, or checkpoints. These results indicate that increased endogenous oxidative stress has broad effects on genome stability and is highly sensitive to the functional state of DNA repair and checkpoints. These findings may provide insight in understanding the consequences of various pathophysiological processes in regard to genomic instability.     

水稻与白叶枯病菌互作机制研究进展

水稻白叶枯病由Xanthomonas oryzae pv.Oryzae(Xoo)致病菌引起,为水稻三大病害之一,对世界水稻生产造成了严重危害.水稻与Xoo互作符合“基因对基因”假说,是研究植物与细菌互作的典型模式系统.水稻基因组以及Xoo基因组测序的完成,极大地推动了水稻-Xoo互作分子机理的研究.就有关水稻与Xoo互作机制的最新研究进展作一概述.     

Understanding Vulvovaginal Candidiasis Through a Community Genomics Approach

Vulvovaginal candidiasis (VVC), predominantly caused by Candida albicans, is one of the most common types of infectious vaginitis. Extensive study has been directed toward understanding host defenses against this infection, and results remain inconclusive. While many have examined the role of innate and cell-mediated immunity, as well as Candida-specific antibodies and the anti-Candida activity of vaginal epithelial cells, little attention has been given to one of the most important players: the vaginal microbiota. Exploring changes in species composition and gene expression within the vaginal community using high-throughput genomic technologies is invaluable to fully understanding Candida pathogenesis and host response to infection. This integrative perspective of pathogenesis, host response and microbial influence are critical to our ability to improve routine gynecologic care and treatment of vaginal infections.     

Gene network analysis in plant development by genomic technologies

The analysis of the gene regulatory networks underlying development is of central importance for a better understanding of the mechanisms that control the formation of the different cell-types, tissues or organs of an organism. The recent invention of genomic technologies has opened the possibility of studying these networks at a global level. In this paper, we summarize some of the recent advances that have been made in the understanding of plant development by the application of genomic technologies. We focus on a few specific processes, namely flower and root development and the control of the cell cycle, but we also highlight landmark studies in other areas that opened new avenues of experimentation or analysis. We describe the methods and the strategies that are currently used for the analysis of plant development by genomic technologies, as well as some of the problems and limitations that hamper their application. Since many genomic technologies and concepts were first developed and tested in organisms other than plants, we make reference to work in non-plant species and compare the current state of network analysis in plants to that in other multicellular organisms.     

The sheep genome contributes to localization of control elements in a human gene with complex regulatory mechanisms

Genes that show complex tissue-specific and temporal control by regulatory elements located outside their promoters present a considerable challenge to identify the sequences involved. The rapid accumulation of genomic sequence information for a number of species has enabled a comparative phylogenetic approach to find important regulatory elements. For some genes, which show a similar pattern of expression in humans and rodents, genomic sequence information for these two species may be sufficient. Others, such as the cystic fibrosis transmembrane conductance regulator (CFTR) gene, show significant divergence in expression patterns between mouse and human, necessitating phylogenetic approaches involving additional species. The ovine CFTR gene has a temporal and spatial expression pattern that is very similar to that of human CFTR. Comparative genomic sequence analysis of ovine and human CFTR identified high levels of homology between the core elements in several potential regulatory elements defined as DNase I hypersensitive sites in human CFTR. These data provide a case for the power of an artiodactyl genome to contribute to the understanding of human genetic disease.     

Cutaneous melanoma: fishing with chips

DNA microarray technology is a versatile platform that allows rapid genetic analysis to take place on a genome-wide scale and has revolutionized the way cancers are studied. This platform has enabled researchers to characterize mechanisms central to tumorigenesis and understand important molecular events in the multi-step tumor progression model of cutaneous melanoma and other cancers. In melanoma, multiple global gene expression profiling studies using various DNA microarray platforms and various experimental designs have been performed. Each study has been able to capture and characterize either the involvement of a novel pathway or a novel cause-effect-relationship. The use of microarrays to define subclasses, to identify differentially regulated genes within a mutational context to analyze epigenetically regulated genes has resulted in an unprecedented understanding of the biology of cutaneous melanoma that may lead to more accurate diagnosis, more comprehensive prognosis, prediction and more effective therapeutic interventions. Related DNA microarray platforms like array-comparative genomic hybridization (CGH) have also been instrumental to identify many non-random chromosomal alterations; however, studies identifying validated targets as a result of CGH are limited. Thus, there exists significant opportunity to discover novel melanoma genes and translate such discoveries into meaningful clinical endpoints. In this review, we focus on various DNA microarray-based studies performed in cutaneous melanoma and summarize our current understanding of the genetics and biology of melanoma progression derived from accumulating genomic information.     

Genomic approaches to fungal pathogenicity

Within a few years, the genome sequences of a large number of medically and agriculturally important fungi will be known. With this resource come the promises of genomic approaches to study pathogenicity and host-fungus interactions. Genomics is particularly attractive for these questions, as conventional genetic and biochemical approaches are limited in many pathogenic fungi. Recent work has applied signature-tagged mutagenesis and DNA microarray analysis to virulence studies in several fungal species, and novel approaches, such as protein arrays and genomic deletion libraries, are being developed in Saccharomyces cerevisiae and have significant potential in other fungi. High-throughput gene-discovery approaches should greatly increase our understanding of fungal pathogenesis.     

Effect of genomic deficiencies on sexual size dimorphism through modification of developmental time in Drosophila melanogaster

Sexual size dimorphism (SSD), a difference in body size between sexes, is common in many taxa. In insects, females are larger than males in >70% of all taxa in most orders. The fruit fly, Drosophila melanogaster is one prominent model organism to investigate SSD since its clear and representative female-biased SSD and its growth regulation are well studied. Elucidating the number and nature of genetic elements that can potentially influence SSD would be helpful in understanding the evolutionary potential of SSD. Here, we investigated the SSD pattern caused by artificially introduced genetic variation in D. melanogaster, and examined whether variation in SSD was mediated by the sex-specific modification of developmental time. To map the genomic regions that had effects on sexual wing size and/or developmental time differences (SDtD), we reanalyzed previously published genome-wide deficiency mapping data to evaluate the effects of 376 isogenic deficiencies covering a total of ~67% of the genomic regions of the second and third chromosomes of D. melanogaster. We found genetic variation in SSD and SDtD generated by genomic deficiencies, and a negative genetic correlation between size and development time. We also found SSD and SDtD allometries that are not qualitatively congruent, which however overall at best only partly help in explaining the patterns found. We identified several genomic deficiencies with the tendency to either exaggerate or suppress SSD, in agreement with quantitative genetic null expectations of many loci with small effects. These novel findings contribute to a better understanding of the evolutionary potential of sexual dimorphism.     

Measurably recombining malaria parasites

Genomic epidemiology has guided research and policy for various viral pathogens and there has been a parallel effort towards using genomic epidemiology to combat diseases that are caused by eukaryotic pathogens, such as the malaria parasite. However, the central concept of viral genomic epidemiology, namely that of measurably mutating pathogens, does not apply easily to sexually recombining parasites. Here we introduce the related but different concept of measurably recombining malaria parasites to promote convergence around a unifying theoretical framework for malaria genomic epidemiology. Akin to viral phylodynamics, we anticipate that an inferential framework developed around recombination will help guide practical research and thus realize the full public health potential of genomic epidemiology for malaria parasites and other sexually recombining pathogens.     

SNP and mutation data on the web - hidden treasures for uncovering

SNP data has grown exponentially over the last two years, SNP database evolution has matched this growth, as initial development of several independent SNP databases has given way to one central SNP database, dbSNP. Other SNP databases have instead evolved to complement this central database by providing gene specific focus and an increased level of curation and analysis on subsets of data, derived from the central data set. By contrast, human mutation data, which has been collected over many years, is still stored in disparate sources, although moves are afoot to move to a similar central database. These developments are timely, human mutation and polymorphism data both hold complementary keys to a better understanding of how genes function and malfunction in disease. The impending availability of a complete human genome presents us with an ideal framework to integrate both these forms of data, as our understanding of the mechanisms of disease increase, the full genomic context of variation may become increasingly significant.     

Molecular features and functional constraints in the evolution of the mammalian X chromosome

Recent advances in genomic sequencing of multiple organisms have fostered significant advances in our understanding of the evolution of the sex chromosomes. The integration of this newly available sequence information with functional data has facilitated a considerable refinement of our conceptual framework of the forces driving this evolution. Here we address multiple functional constraints that were encountered in the evolution of the X chromosome and the impact that this evolutionary history has had on its modern behavior.