The animal in the genome: comparative genomics and evolution

Comparisons between completely sequenced metazoan genomes have generally emphasized how similar their encoded protein content is, even when the comparison is between phyla. Given the manifest differences between phyla and, in particular, intuitive notions that some animals are more complex than others, this creates something of a paradox. Simplistic explanations have included arguments such as increased numbers of genes; greater numbers of protein products produced through alternative splicing; increased numbers of regulatory non-coding RNAs and increased complexity of the cis-regulatory code. An obvious value of complete genome sequences lies in their ability to provide us with inventories of such components. I examine progress being made in linking genome content to the pattern of animal evolution, and argue that the gap between genomic and phenotypic complexity can only be understood through the totality of interacting components.     

Comparative genomics of insect-symbiotic bacteria: influence of host environment on microbial genome composition

Commensal symbionts, thought to be intermediary amid obligate mutualists and facultative parasites, offer insight into forces driving the evolutionary transition into mutualism. Using macroarrays developed for a close relative, Escherichia coli, we utilized a heterologous array hybridization approach to infer the genomic compositions of a clade of bacteria that have recently established symbiotic associations: Sodalis glossinidius with the tsetse fly (Diptera, Glossina spp.) and Sitophilus oryzae primary endosymbiont (SOPE) with the rice weevil (Coleoptera, Sitophilus oryzae). Functional biologies within their hosts currently reflect different forms of symbiotic associations. Their hosts, members of distant insect taxa, occupy distinct ecological niches and have evolved to survive on restricted diets of blood for tsetse and cereal for the rice weevil. Comparison of genome contents between the two microbes indicates statistically significant differences in the retention of genes involved in carbon compound catabolism, energy metabolism, fatty acid metabolism, and transport. The greatest reductions have occurred in carbon catabolism, membrane proteins, and cell structure-related genes for Sodalis and in genes involved in cellular processes (i.e., adaptations towards cellular conditions) for SOPE. Modifications in metabolic pathways, in the form of functional losses complementing particularities in host physiology and ecology, may have occurred upon initial entry from a free-living to a symbiotic state. It is possible that these adaptations, streamlining genomes, act to make a free-living state no longer feasible for the harnessed microbe.     

蚯蚓基因组学的研究进展: 基于全基因组及线粒体基因组

蚯蚓被喻为土壤中的“生态系统工程师”, 具有高度的多样性且在全世界都有分布, 被用作土壤健康的指示生物。蚯蚓具有极强的环境适应能力, 在不断适应的过程中促进了自身基因组的进化。本文对近年来蚯蚓全基因组以及线粒体基因组的研究进展进行了综述。蚯蚓全基因组的测序、拼装和分析为研究蚯蚓生态学、污染物对蚯蚓致毒的分子机制、免疫防御的分子机制、蚯蚓再生的分子机制等奠定基础。而线粒体基因组多应用于蚯蚓分子系统发育方面的研究, 目前已有多种蚯蚓通过线粒体基因组测序完成了物种的鉴定。本文建议今后重点开展以下几方面的研究: (1)针对现有的4种蚯蚓全基因组测序结果, 进一步进行比较基因组学、进化基因组学和功能基因组学的研究。(2)完善不同种蚯蚓的基因文库和表达序列标签。(3)建立线粒体基因组、全基因组与蚯蚓物种多样性的关联分析。     

Tick genomics: the Ixodes genome project and beyond

Ticks and mites (subphylum Chelicerata; subclass Acari) include important pests of animals and plants worldwide. The Ixodes scapularis (black-legged tick) genome sequencing project marks the beginning of the genomics era for the field of acarology. This project is the first to sequence the genome of a blood-feeding tick vector of human disease and a member of the subphylum Chelicerata. Genome projects for other species of Acari are forthcoming and their genome sequences will likely feature significantly in the future of tick research. Parasitologists interested in advancing the field of tick genomics research will be faced with specific challenges. The development of genetic tools and resources, and the size and repetitive nature of tick genomes are important considerations. Innovative approaches may be required to sequence, assemble, annotate and analyse tick genomes. Overcoming these challenges will enable scientists to investigate the genes and genome organisation of this important group of arthropods and may ultimately lead to new solutions for control of ticks and tick-borne diseases.     

Methods in comparative genomics: genome correspondence, gene identification and regulatory motif discovery.

In Kellis et al. (2003), we reported the genome sequences of S. paradoxus, S. mikatae, and S. bayanus and compared these three yeast species to their close relative, S. cerevisiae. Genomewide comparative analysis allowed the identification of functionally important sequences, both coding and noncoding. In this companion paper we describe the mathematical and algorithmic results underpinning the analysis of these genomes. (1) We present methods for the automatic determination of genome correspondence. The algorithms enabled the automatic identification of orthologs for more than 90% of genes and intergenic regions across the four species despite the large number of duplicated genes in the yeast genome. The remaining ambiguities in the gene correspondence revealed recent gene family expansions in regions of rapid genomic change. (2) We present methods for the identification of protein-coding genes based on their patterns of nucleotide conservation across related species. We observed the pressure to conserve the reading frame of functional proteins and developed a test for gene identification with high sensitivity and specificity. We used this test to revisit the genome of S. cerevisiae, reducing the overall gene count by 500 genes (10% of previously annotated genes) and refining the gene structure of hundreds of genes. (3) We present novel methods for the systematic de novo identification of regulatory motifs. The methods do not rely on previous knowledge of gene function and in that way differ from the current literature on computational motif discovery. Based on genomewide conservation patterns of known motifs, we developed three conservation criteria that we used to discover novel motifs. We used an enumeration approach to select strongly conserved motif cores, which we extended and collapsed into a small number of candidate regulatory motifs. These include most previously known regulatory motifs as well as several noteworthy novel motifs. The majority of discovered motifs are enriched in functionally related genes, allowing us to infer a candidate function for novel motifs. Our results demonstrate the power of comparative genomics to further our understanding of any species. Our methods are validated by the extensive experimental knowledge in yeast and will be invaluable in the study of complex genomes like that of the human.     

Chromosome conformation capture technologies and their impact in understanding genome function

It has been more than a decade since the first chromosome conformation capture (3C) assay was described. The assay was originally devised to measure the frequency with which two genomic loci interact within the three-dimensional (3D) nuclear space. Over time, this method has evolved both qualitatively and quantitatively, from detection of pairwise interaction of two unique loci to generating maps for the global chromatin interactome. Combined with the analysis of the epigenetic chromatin context, these advances led to the unmasking of general genome folding principles. The evolution of 3C-based methods has been supported first by the revolution in ChIP and then by sequencing-based approaches, methods that were primarily tools to study the unidimensional genome. The gradual improvement of 3C-based methods illustrates how the field adapted to the need to gradually address more subtle questions, beginning with enquiries of reductionist nature to reach more holistic perspectives, as the technology advanced, in a process that is greatly improving our knowledge on genome behavior and regulation. Here, we describe the evolution of 3C and other 3C-based methods for the analysis of chromatin interactions, along with a brief summary of their contribution in uncovering the significance of the three-dimensional world within the nucleus. We also discuss their inherent limitations and caveats in order to provide a critical view of the power and the limits of this technology.     

基因组水平的基因挖掘与功能分析方法的探讨

为了实现基因组中特定基因功能的注释,研究者提出一种新的思路,即利用对目的基因启动子上游的顺式元件的功能的分析,进一步来推断目的基因的功能。在此主要对基因组水平的基因挖掘与功能分析方法及其研究进展进行了探讨。     

Medaka genomics: a bridge between mutant phenotype and gene function

Recent advances in medaka genetics have proven that the medakafish is an excellent model system for developmental and evolutionary biology studies and that it can complement similar studies in zebrafish. Large-scale mutagenesis projects are now being conducted by several groups in Japan and are delivering a vastly expanded pool of medaka mutant stocks. This growing availability of genomic resources will greatly accelerate progress in moving from mutant phenotypes to the elucidation of gene function. This phenotype-driven approach can be expected to lead to the identification and characterization of novel genes and pathways in vertebrate genomes. This review discusses the current state of medaka genomic resources, the state of medaka gene mapping and medaka genome sequencing projects.     

Comparative genomics of natural killer cell receptor gene clusters

Many receptors on natural killer (NK) cells recognize major histocompatibility complex class I molecules in order to monitor unhealthy tissues, such as cells infected with viruses, and some tumors. Genes encoding families of NK receptors and related sequences are organized into two main clusters in humans: the natural killer complex on Chromosome 12p13.1, which encodes C-type lectin molecules, and the leukocyte receptor complex on Chromosome 19q13.4, which encodes immunoglobulin superfamily molecules. The composition of these gene clusters differs markedly between closely related species, providing evidence for rapid, lineage-specific expansions or contractions of sets of loci. The choice of NK receptor genes is polarized in the two species most studied, mouse and human. In mouse, the C-type lectin-related Ly49 gene family predominates. Conversely, the single Ly49 sequence is a pseudogene in humans, and the immunoglobulin superfamily KIR gene family is extensive. These different gene sets encode proteins that are comparable in function and genetic diversity, even though they have undergone species-specific expansions. Understanding the biological significance of this curious situation may be aided by studying which NK receptor genes are used in other vertebrates, especially in relation to species-specific differences in genes for major histocompatibility complex class I molecules.     

Structural genomics and its importance for gene function analysis

Structural genomics projects aim to solve the experimental structures of all possible protein folds. Such projects entail a conceptual shift from traditional structural biology in which structural information is obtained on known proteins to one in which the structure of a protein is determined first and the function assigned only later. Whereas the goal of converting protein structure into function can be accomplished by traditional sequence motif-based approaches, recent studies have shown that assignment of a protein's biochemical function can also be achieved by scanning its structure for a match to the geometry and chemical identity of a known active site. Importantly, this approach can use low-resolution structures provided by contemporary structure prediction methods. When applied to genomes, structural information (either experimental or predicted) is likely to play an important role in high-throughput function assignment.     

Sulfolobus genome: from genomics to biology

Major progress in sequencing the genome of Sulfolobus solfataricus has been closely concerted with the characterization and sequencing of many extrachromosomal genetic elements, including viruses, cryptic plasmids and conjugative plasmids, as well as mobile archaeal introns and transposons. The latter have provided a basis for developing the first generation of vectors that are now being used to study the genetics of Sulfolobus and other Archaea.     

Comparative genomics and genome evolution in yeasts

Yeasts provide a powerful model system for comparative genomics research. The availability of multiple complete genome sequences from different fungal groups--currently 18 hemiascomycetes, 8 euascomycetes and 4 basidiomycetes--enables us to gain a broad perspective on genome evolution. The sequenced genomes span a continuum of divergence levels ranging from multiple individuals within a species to species pairs with low levels of protein sequence identity and no conservation of gene order. One of the most interesting emerging areas is the growing number of events such as gene losses, gene displacements and gene relocations that can be attributed to the action of natural selection.