Sequencing the chimpanzee genome: insights into human evolution and disease

Large-scale sequencing of the chimpanzee genome is now imminent. Beyond the inherent fascination of comparing the sequence of the human genome with that of our closest living relative, this project is likely to yield tangible scientific benefits in two areas. First, the discovery of functionally important mutations that are specific to the human lineage offers a new path towards medical benefits. Second, chimpanzee-human comparisons are likely to yield molecular insights into how new biological characteristics evolve--findings that might be relevant throughout the tree of life.     

The bovine lactation genome: insights into the evolution of mammalian milk

One of the major genomics challenges is to better understand how correct gene expression is orchestrated. Recent studies have shown how spatial chromatin organization is critical in the regulation of gene expression. Here, we developed a suite of computer programs to identify chromatin conformation signatures with 5C technology http://Dostielab.biochem.mcgill.ca. We identified dynamic HoxA cluster chromatin conformation signatures associated with cellular differentiation. Genome-wide chromatin conformation signature identification might uniquely identify disease-associated states and represent an entirely novel class of human disease biomarkers.     

The bovine lactation genome: insights into the evolution of mammalian milk

Background

The newly assembled Bos taurus genome sequence enables the linkage of bovine milk and lactation data with other mammalian genomes.

Results

Using publicly available milk proteome data and mammary expressed sequence tags, 197 milk protein genes and over 6,000 mammary genes were identified in the bovine genome. Intersection of these genes with 238 milk production quantitative trait loci curated from the literature decreased the search space for milk trait effectors by more than an order of magnitude. Genome location analysis revealed a tendency for milk protein genes to be clustered with other mammary genes. Using the genomes of a monotreme (platypus), a marsupial (opossum), and five placental mammals (bovine, human, dog, mice, rat), gene loss and duplication, phylogeny, sequence conservation, and evolution were examined. Compared with other genes in the bovine genome, milk and mammary genes are: more likely to be present in all mammals; more likely to be duplicated in therians; more highly conserved across Mammalia; and evolving more slowly along the bovine lineage. The most divergent proteins in milk were associated with nutritional and immunological components of milk, whereas highly conserved proteins were associated with secretory processes.

Conclusions

Although both copy number and sequence variation contribute to the diversity of milk protein composition across species, our results suggest that this diversity is primarily due to other mechanisms. Our findings support the essentiality of milk to the survival of mammalian neonates and the establishment of milk secretory mechanisms more than 160 million years ago.     

Microbial genome analysis: insights into virulence, host adaptation and evolution

Genome analysis of microbial pathogens has provided unique insights into their virulence, host adaptation and evolution. Common themes have emerged, including lateral gene transfer among enteric pathogens, genome decay among obligate intracellular pathogens and antigenic variation among mucosal pathogens. The advent of post-genomic approaches and the sequencing of the human genome will enable scientists to investigate the complex and dynamic interplay between host and pathogen. This wealth of information will catalyse the development of new intervention strategies to reduce the burden of microbial-related disease.     

Cluster K mycobacteriophages: insights into the evolutionary origins of mycobacteriophage TM4

Five newly isolated mycobacteriophages--Angelica, CrimD, Adephagia, Anaya, and Pixie--have similar genomic architectures to mycobacteriophage TM4, a previously characterized phage that is widely used in mycobacterial genetics. The nucleotide sequence similarities warrant grouping these into Cluster K, with subdivision into three subclusters: K1, K2, and K3. Although the overall genome architectures of these phages are similar, TM4 appears to have lost at least two segments of its genome, a central region containing the integration apparatus, and a segment at the right end. This suggests that TM4 is a recent derivative of a temperate parent, resolving a long-standing conundrum about its biology, in that it was reportedly recovered from a lysogenic strain of Mycobacterium avium, but it is not capable of forming lysogens in any mycobacterial host. Like TM4, all of the Cluster K phages infect both fast- and slow-growing mycobacteria, and all of them--with the exception of TM4--form stable lysogens in both Mycobacterium smegmatis and Mycobacterium tuberculosis; immunity assays show that all five of these phages share the same immune specificity. TM4 infects these lysogens suggesting that it was either derived from a heteroimmune temperate parent or that it has acquired a virulent phenotype. We have also characterized a widely-used conditionally replicating derivative of TM4 and identified mutations conferring the temperature-sensitive phenotype. All of the Cluster K phages contain a series of well conserved 13 bp repeats associated with the translation initiation sites of a subset of the genes; approximately one half of these contain an additional sequence feature composed of imperfectly conserved 17 bp inverted repeats separated by a variable spacer. The K1 phages integrate into the host tmRNA and the Cluster K phages represent potential new tools for the genetics of M. tuberculosis and related species.     

New insights into the molecular mechanisms of evolution: stress increases genetic diversity

The mechanisms of stress-induced mutagenesis in prokaryotes and realization of reserved (preaccumulated) genetic variation in eukaryotes are considered. In prokaryotes, replication becomes error-prone in stress because of the induction of the SOS response and the inactivation of the mismatch repair system; stress also increases the transposition rate and the efficiency of interspecific gene transfer. In eukaryotes, chaperone HSP90, which restores the native folding of mutant proteins (e.g., signal transduction and morphogenetic proteins) in normal conditions, fails to do so in stress, which leads to abrupt expression of multiple mutations earlier reserved in the corresponding genes. The role of these mechanisms in the evolution of prokaryotes and eukaryotes is discussed.     

The complete mitochondrial genome of Fusarium oxysporum: insights into fungal mitochondrial evolution

The complete mitochondrial DNA (mtDNA) sequence was determined for the phytopathogenic fungus Fusarium oxysporum. It is 34,477 bp long, maps circularly, and encodes for 14 protein-coding, 25 tRNA and 2 rRNA genes. The nucleotide and amino acid data sets from its 14 concatenated protein-coding mitochondrial (mt) genes were used along with gene order comparisons for an extensive phylogenetic study of the Subphylum Pezizomycotina. Our results are in agreement with current taxonomic treatments and additionally provide better statistical support for all relationships within Pezizomycotina when compared to analyses based on single or few gene data sets. The gene order of F. oxysporum was consistent with that established in the order Hypocreales (Class: Sordariomycetes) and enhanced previous suppositions on the ancestral state of Sordariomycetes. In comparison with mt genomes of the other orders it added further insights to the evolution of Pezizomycotina.     

Influenza genome diversity and evolution

The influenza viruses contain highly variable genomes and are able to infect a wide range of host species. Large-scale sequencing projects have collected abundant influenza sequence data for assessing influenza genome diversity and evolution. This work reviews current influenza sequence databases characteristics and statistics, as well as recent studies utilizing these databases to unravel influenza virus diversity and evolution. Also discussed are the newest deep sequencing methods and their applications to influenza virus research.     

The draft genome of Actinia tenebrosa reveals insights into toxin evolution

Sea anemones have a wide array of toxic compounds (peptide toxins found in their venom) which have potential uses as therapeutics. To date, the majority of studies characterizing toxins in sea anemones have been restricted to species from the superfamily, Actinioidea. No highly complete draft genomes are currently available for this superfamily, however, highlighting our limited understanding of the genes encoding toxins in this important group. Here we have sequenced, assembled, and annotated a draft genome for Actinia tenebrosa. The genome is estimated to be approximately 255 megabases, with 31,556 protein‐coding genes. Quality metrics revealed that this draft genome matches the quality and completeness of other model cnidarian genomes, including Nematostella, Hydra, and Acropora. Phylogenomic analyses revealed strong conservation of the Cnidaria and Hexacorallia core‐gene set. However, we found that lineage‐specific gene families have undergone significant expansion events compared with shared gene families. Enrichment analysis performed for both gene ontologies, and protein domains revealed that genes encoding toxins contribute to a significant proportion of the lineage‐specific genes and gene families. The results make clear that the draft genome of A. tenebrosa will provide insight into the evolution of toxins and lineage‐specific genes, and provide an important resource for the discovery of novel biological compounds.     

Complete genome sequences of 138 mycobacteriophages

Bacteriophages are the most numerous biological entities in the biosphere, and although their genetic diversity is high, it remains ill defined. Mycobacteriophages-the viruses of mycobacterial hosts-provide insights into this diversity as well as tools for manipulating Mycobacterium tuberculosis. We report here the complete genome sequences of 138 new mycobacteriophages, which-together with the 83 mycobacteriophages previously reported-represent the largest collection of phages known to infect a single common host, Mycobacterium smegmatis mc(2) 155.     

TAR cloning: insights into gene function, long-range haplotypes and genome structure and evolution

The structural and functional analysis of mammalian genomes would benefit from the ability to isolate from multiple DNA samples any targeted chromosomal segment that is the size of an average human gene. A cloning technique that is based on transformation-associated recombination (TAR) in the yeast Saccharomyces cerevisiae satisfies this need. It is a unique tool to selectively recover chromosome segments that are up to 250 kb in length from complex genomes. In addition, TAR cloning can be used to characterize gene function and genome variation, including polymorphic structural rearrangements, mutations and the evolution of gene families, and for long-range haplotyping.     

Foliar architecture of vanilloid orchids: insights into the evolution of reticulate leaf venation in monocotyledons

Leaves of representative taxa within the vanilloid clade of Orchidaceae were cleared and their venation patterns studied. Within subtribe Pogoniinae, Isotria and Pogonia exhibit a prominent reticulate venation pattern, although only Pogonia ophioglossoides is characterized by free vein endings. Within subtribe Vanillinae, all species of Epistephium , as well as the New Caledonian endemics, Eriaxis rigida and Clematepistephium smilacifolium , have reticulate-veined leaves that are characterized by numerous free vein endings. Leaves of most species of Vanilla exhibit a parallel-veined pattern stereotypical of monocots, although branched secondaries with free endings were observed in V. africana. Most members of subtribe Galeolinae are 'saprophytes' with reduced bract-like leaves. Vascular bundles enter these leaf-homologues in a parallel manner, but quickly ram+ throughout the tissue in an irregular manner. Leaf venation is used to hypothesize patterns of generic relationships within the vanilloid clade. Molecular evidence for phylogenetic relationships among angiosperms indicates that reticulate leaf venation has arisen independently in several unrelated monocot families, including the vanilloid Orchidaceae, perhaps by a similar evolutionary scenario.     

High resolution structure of Deinococcus bacteriophytochrome yields new insights into phytochrome architecture and evolution

Phytochromes are red/far red light photochromic photoreceptors that direct many photosensory behaviors in the bacterial, fungal, and plant kingdoms. They consist of an N-terminal domain that covalently binds a bilin chromophore and a C-terminal region that transmits the light signal, often through a histidine kinase relay. Using x-ray crystallography, we recently solved the first three-dimensional structure of a phytochrome, using the chromophore-binding domain of Deinococcus radiodurans bacterial phytochrome assembled with its chromophore, biliverdin IXalpha. Now, by engineering the crystallization interface, we have achieved a significantly higher resolution model. This 1.45A resolution structure helps identify an extensive buried surface between crystal symmetry mates that may promote dimerization in vivo. It also reveals that upon ligation of the C3(2) carbon of biliverdin to Cys(24), the chromophore A-ring assumes a chiral center at C2, thus becoming 2(R),3(E)-phytochromobilin, a chemistry more similar to that proposed for the attached chromophores of cyanobacterial and plant phytochromes than previously appreciated. The evolution of bacterial phytochromes to those found in cyanobacteria and higher plants must have involved greater fitness using more reduced bilins, such as phycocyanobilin, combined with a switch of the attachment site from a cysteine near the N terminus to one conserved within the cGMP phosphodiesterase/adenyl cyclase/FhlA domain. From analysis of site-directed mutants in the D. radiodurans phytochrome, we show that this bilin preference was partially driven by the change in binding site, which ultimately may have helped photosynthetic organisms optimize shade detection. Collectively, these three-dimensional structural results better clarify bilin/protein interactions and help explain how higher plant phytochromes evolved from prokaryotic progenitors.     

薏苡黑粉菌基因组测序揭示其物种分类及适应性进化

以薏苡黑粉菌病瘿为研究对象,采用固体和液体培养方法对薏苡黑粉菌进行分离纯化培养和形态观察;利用Illumina、Pacbio测序和Hi-C辅助基因组组装技术对黑粉菌进行测序、组装和注释,分析其基因组结构和组成特征。通过与其他6个黑粉菌物种基因组进行比较基因组学研究,分析薏苡黑粉菌的基因家族进化和系统发育关系。在pH 7的固体PDA和液体PDB培养基中实现了薏苡黑粉菌的纯化培养,固体培养菌落表现为白色、表面隆起、具褶皱,较湿润且不透明的形态特征。Illumina、Pacbio和Hi-C组装结果显示,薏苡黑粉菌具有20对染色体(2n=40),基因组大小20.093 417 Mb,GC含量53.81%;共预测和注释到7 476个蛋白编码基因和164个非编码基因,占整个基因组长度的61.02%和0.285 3%;查找到3 674个散在重复序列和8 139个串联重复序列,分别占整个基因组长度的2.754 4%和1.605 4%。同源基因家族聚类显示,7个黑粉菌物种Ustilago coicis、U. bromivora、U. maydis、U. hordei、Sporisorium reilianum、S. scitamineum和S. graminicola的编码基因被聚类为6 999个基因家族,其中共有基因家族5 379个。薏苡黑粉菌包含5 339个单拷贝基因、105个多拷贝基因、89个特异基因、752个其他基因和188个未分类基因。基因家族进化和系统发育聚类表明,薏苡黑粉菌U. coicis在~60.9 MYA分化出来,与雀麦黑粉菌U. bromivova、大麦坚黑粉菌U. hordei聚为一支,表现为更近的亲缘关系;而玉米黑粉菌U. maydis在~66.6 MYA分化出来与3个孢堆黑粉菌物种S. scitamineum、S. graminicola和S. reilianum聚为一支。     

A chromosome-level genome assembly of Ostrea denselamellosa provides initial insights into its evolution

The oyster Ostrea denselamellosa is a live-bearing species with a sharp decline in the natural population. Despite recent breakthroughs in long-read sequencing, high quality genomic data are very limited in O. denselamellosa. Here, we carried out the first whole genome sequencing at the chromosome-level in O. denselamellosa. Our studies yielded a 636 Mb assembly with scaffold N50 around 71.80 Mb. 608.3 Mb (95.6% of the assembly) were anchored to 10 chromosomes. A total of 26,412 protein-coding genes were predicted, of which 22,636 (85.7%) were functionally annotated. By comparative genomics, we found that long interspersed nuclear element (LINE) and short interspersed nuclear element (SINE) made up a larger proportion in O. denselamellosa genome than in other oysters'. Moreover, gene family analysis showed some initial insight into its evolution. This high-quality genome of O. denselamellosa provides a valuable genomic resource for studies of evolution, adaption and conservation in oysters.