Genome-wide expression dynamics of a marine virus and host reveal features of co-evolution

Interactions between bacterial hosts and their viruses (phages) lead to reciprocal genome evolution through a dynamic co-evolutionary process. Phage-mediated transfer of host genes--often located in genome islands--has had a major impact on microbial evolution. Furthermore, phage genomes have clearly been shaped by the acquisition of genes from their hosts. Here we investigate whole-genome expression of a host and phage, the marine cyanobacterium Prochlorococcus MED4 and the T7-like cyanophage P-SSP7, during lytic infection, to gain insight into these co-evolutionary processes. Although most of the phage genome was linearly transcribed over the course of infection, four phage-encoded bacterial metabolism genes formed part of the same expression cluster, even though they are physically separated on the genome. These genes--encoding photosystem II D1 (psbA), high-light inducible protein (hli), transaldolase (talC) and ribonucleotide reductase (nrd)--are transcribed together with phage DNA replication genes and seem to make up a functional unit involved in energy and deoxynucleotide production for phage replication in resource-poor oceans. Also unique to this system was the upregulation of numerous genes in the host during infection. These may be host stress response genes and/or genes induced by the phage. Many of these host genes are located in genome islands and have homologues in cyanophage genomes. We hypothesize that phage have evolved to use upregulated host genes, leading to their stable incorporation into phage genomes and their subsequent transfer back to hosts in genome islands. Thus activation of host genes during infection may be directing the co-evolution of gene content in both host and phage genomes.     

Tissue-specific expression of rat myosin light-chain 2 gene in transgenic mice

One approach to determining how the differential expression of specific genes is regulated in higher organisms is to introduce cloned copies of the genes (or parts of the genes) into the genomes of individual organisms from the very beginning of their development. The way in which the exogenous genetic information behaves during the development of the experimental organisms can then provide a means of defining the DNA sequences that restrict the expression of the gene to specific cell types and times of development. So far, several different genes have been introduced into the genomes of mice, but in only a few cases have the exogenous genes retained the tissue specificity of expression of the equivalent endogenous genes. I report here that in two out of three 'transgenic' mice carrying copies of the rat gene for skeletal muscle myosin light chain 2, the exogenous gene is expressed specifically in skeletal muscle cells. The sequences contained in the cloned copy of the myosin light-chain 2 gene used in these experiments are thus sufficient to confer a tissue-specific pattern of expression.     

Genome divergence in two Prochlorococcus ecotypes reflects oceanic niche differentiation

The marine unicellular cyanobacterium Prochlorococcus is the smallest-known oxygen-evolving autotroph. It numerically dominates the phytoplankton in the tropical and subtropical oceans, and is responsible for a significant fraction of global photosynthesis. Here we compare the genomes of two Prochlorococcus strains that span the largest evolutionary distance within the Prochlorococcus lineage and that have different minimum, maximum and optimal light intensities for growth. The high-light-adapted ecotype has the smallest genome (1,657,990 base pairs, 1,716 genes) of any known oxygenic phototroph, whereas the genome of its low-light-adapted counterpart is significantly larger, at 2,410,873 base pairs (2,275 genes). The comparative architectures of these two strains reveal dynamic genomes that are constantly changing in response to myriad selection pressures. Although the two strains have 1,350 genes in common, a significant number are not shared, and these have been differentially retained from the common ancestor, or acquired through duplication or lateral transfer. Some of these genes have obvious roles in determining the relative fitness of the ecotypes in response to key environmental variables, and hence in regulating their distribution and abundance in the oceans.     

Gene transfer to the nucleus and the evolution of chloroplasts

Photosynthetic eukaryotes, particularly unicellular forms, possess a fossil record that is either wrought with gaps or difficult to interpret, or both. Attempts to reconstruct their evolution have focused on plastid phylogeny, but were limited by the amount and type of phylogenetic information contained within single genes. Among the 210 different protein-coding genes contained in the completely sequenced chloroplast genomes from a glaucocystophyte, a rhodophyte, a diatom, a euglenophyte and five land plants, we have now identified the set of 45 common to each and to a cyanobacterial outgroup genome. Phylogenetic inference with an alignment of 11,039 amino-acid positions per genome indicates that this information is sufficient--but just rarely so--to identify the rooted nine-taxon topology. We mapped the process of gene loss from chloroplast genomes across the inferred tree and found that, surprisingly, independent parallel gene losses in multiple lineages outnumber phylogenetically unique losses by more that 4:1. We identified homologues of 44 different plastid-encoded proteins as functional nuclear genes of chloroplast origin, providing evidence for endosymbiotic gene transfer to the nucleus in plants.     

移位变换下一类进化树的重构问题

讨论多重基因组在移位变换下的一类进化树的重构问题：给定一个由若干基因组组成的集族∏与另一个基因组A，其中所有基因组由同样的一些有向的基因组成，且每个基因组由相同数目的染色体组成，每一个基因在每个基因组中恰好出现一次，所有基因组有相同的尾基因集合，要求构造一个由A到∏的进化树，使得沿此树所发生的移位变换数目最少．给出由一个基因组生成一些给定基因组的近似算法；在一个特殊情况下给出其多项式时间算法．     

引起人非典型性肺炎的冠状病毒基因组与其它冠状病毒基因组的初步比较

一种在世界范围内突然爆发的致命流行病——急性呼吸窘迫综合症(SARS)击倒了数干人，一种全新的冠状病毒被认为是其病原．5个SARS相关冠状病毒的全基因组序列已经完成．我们进行了SARS相关冠状病毒和其它冠状病毒的基因组进化分析和序列比较，结果显示：1．SARS相关冠状病毒不直接来自于任何已知的冠状病毒；2．E蛋白的基因可能是在近期从其它病毒横向转移到SARS病毒中来的；3．Sl和S2基因发生了较大范围的缺失或插入突变．这些基因横向转移和突变改变了SARS相关病毒的表面结构和抗原性，极有可能是导致其获得侵染人类细胞的主要原因．     

利用乙醇脱氢酶基因证据揭示稻属CCDD异源四倍体中染色体组的起源

对稻属异源四倍体中染色体组C和D以及稻属现存的所有二倍体染色体组A、B、C、E、F的乙醇脱氢酶基因（Adh1）片段分别进行PCR扩增、克隆和序列测定,并以G染色体组序列作为外类群,采用PAUP运算软件中的简约性方法对所测定的序列进行了系统发育分析．结果表明：（1）3个CCDD四倍体是同一次杂交事件的产物;（2）四倍体中的C染色体组和亚洲二倍体中的C染色体组表现出更近的系统发育关系;（3）D染色体组和E染色体组表现出较近的亲缘关系,二者可能有共同的祖先．     

Herpesvirus saimiri encodes homologues of G protein-coupled receptors and cyclins.

Herpesvirus saimiri (HVS) is a T-lymphotropic gammaherpesvirus which establishes asymptomatic infections in its natural host the squirrel monkey (Saimiri sciureus), but which causes fatal lymphoproliferative diseases in other New World primates. Sequencing studies show HVS is closely related to the human B-lymphotropic gammaherpesvirus Epstein-Barr virus (EBV). However, despite the general colinearity between the genomes of HVS and EBV, HVS contains genes not found in EBV or in the genomes of any of the other sequenced herpesviruses. We have identified two genes, occurring in a region of divergence between HVS and EBV, that have cellular homologues. One of these, ECRF3, is homologous to the genes encoding the human cytomegalovirus (HCMV) and cellular G protein-coupled receptor family of proteins. The other HVS gene, ECLF2, is homologous to the genes encoding cellular cyclins and to our knowledge is the first reported example of a viral cyclin. The presence of G protein-coupled receptor and cyclin homologues in HVS suggests that these genes may be important in the regulation of viral and cellular processes during productive and/or latent infection of host cells, and in particular may be of relevance in the transformation and rapid proliferation of T cells during HVS infections of hosts susceptible to HVS-induced lymphoproliferative diseases.     

Endogenous viral genes are non-essential in the chicken.

DNA sequences homologous to the genomes of type C retroviruses are widespread among vertebrates. Ten genetic loci containing endogenous viral DNA sequences have been documented in the white Leghorn chicken alone. Six of these genetic loci are associated with the production of virus or of viral proteins in embryonic fibroblasts (refs 2--4, and S.M.A., L, B. Crittenden and E.G.B., in preparation) and one of the loci may be expressed in the erythroblasts of 5-day-old embryos. The abiquitous presence of endogenous viral genes among vertebrate species and the association of their expression with development of the haematopoietic system in the mouse have led to the proposal that these genes are involved in ontogeny. In addition, the genes may be implicated in oncogenesis as in the case of the AKR mouse in which a high incidence of spontaneous leukaemia is associated with the expression of endogenous murine laukaemia virus genomes. We report here the production of a fertile rooster which lacks avian leukosis virus-related endogenous viral genes and which seems to be completely normal and healthy. Thus, endogenous viral genes are apparently not essential for the normal development of the chicken. An endogenous virus-free state has also been reported for three species of jungle fowl and for the B-type viral genes of the mouse.     

Self-splicing introns in tRNA genes of widely divergent bacteria.

The organization of eukaryotic genes into exons separated by introns has been considered as a primordial arrangement but because it does not exist in eubacterial genomes it may be that introns are relatively recent acquisitions. A self-splicing group I intron has been found in cyanobacteria at the same position of the same gene (that encoding leucyl transfer RNA, UAA anticodon) as a similar group I intron of chloroplasts, which indicates that this intron predates the invasion of eukaryotic cells by cyanobacterial endosymbionts. But it is not clear from this isolated example whether introns are more generally present in different genes or in more diverse branches of the eubacteria. Many mitochondria have intron-rich genomes and were probably derived from the alpha subgroup of the purple bacteria (or Proteobacteria), so ancient introns might also have been retained in these bacteria. We describe here the discovery of two small (237 and 205 nucleotides) self-splicing group I introns in members of two proteobacterial subgroups, Agrobacterium tumefaciens (alpha) and Azoarcus sp. (beta). The introns are inserted in genes for tRNA(Arg) and tRNA(Ile), respectively, after the third anticodon nucleotide. Their occurrence in different genes of phylogenetically diverse bacteria indicates that group I introns have a widespread distribution among eubacteria.     

Origin and evolution of new genes

Organisms have variable gcnome sizes and contain different numbers of genes. This difference demonstrates that new gene origination is a fundamental process in evolutionary biology. Though the study of the origination of new genes dated back more than half a century ago, it is not until the 1990s when the first young genejingwei was found that empirical investigation of the molecular mechanisms of origination of new genes became possible. In the recent years, several young genes were identified and the studies on these genes have greatly enriched the knowledge of this field. Yet more details in a general picture of new genes origination are to be clarified. We have developed a systematic approach to searching for young genes at the genomic level, in the hope to summarize a general pattern of the origination and evolution of new genes, such as the rate of new gene appearance, impact of new genes on their host genomes, etc.     

Seed development: Early paternal gene activity in Arabidopsis.

Both parental genomes are expressed during embryogenesis, although the time of activation of the paternally inherited genes varies between organisms. Results reported by Vielle-Calzada et al. have suggested that delayed activation of the paternal genome seems to be the rule in plant development. We find, however, that during early embryogenesis in Arabidopsis, paternal genes are expressed and are sufficient for normal development. Our findings indicate that there is no overall maternal control of early embryogenesis, and that the contribution of the parental alleles needs to be assessed for each gene individually.     

Evidence for lateral gene transfer between Archaea and bacteria from genome sequence of Thermotoga maritima.

The 1,860,725-base-pair genome of Thermotoga maritima MSB8 contains 1,877 predicted coding regions, 1,014 (54%) of which have functional assignments and 863 (46%) of which are of unknown function. Genome analysis reveals numerous pathways involved in degradation of sugars and plant polysaccharides, and 108 genes that have orthologues only in the genomes of other thermophilic Eubacteria and Archaea. Of the Eubacteria sequenced to date, T. maritima has the highest percentage (24%) of genes that are most similar to archaeal genes. Eighty-one archaeal-like genes are clustered in 15 regions of the T. maritima genome that range in size from 4 to 20 kilobases. Conservation of gene order between T. maritima and Archaea in many of the clustered regions suggests that lateral gene transfer may have occurred between thermophilic Eubacteria and Archaea.     

Patterns of somatic mutation in human cancer genomes

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.     

The DNA sequence and analysis of human chromosome 14

Chromosome 14 is one of five acrocentric chromosomes in the human genome. These chromosomes are characterized by a heterochromatic short arm that contains essentially ribosomal RNA genes, and a euchromatic long arm in which most, if not all, of the protein-coding genes are located. The finished sequence of human chromosome 14 comprises 87,410,661 base pairs, representing 100% of its euchromatic portion, in a single continuous segment covering the entire long arm with no gaps. Two loci of crucial importance for the immune system, as well as more than 60 disease genes, have been localized so far on chromosome 14. We identified 1,050 genes and gene fragments, and 393 pseudogenes. On the basis of comparisons with other vertebrate genomes, we estimate that more than 96% of the chromosome 14 genes have been annotated. From an analysis of the CpG island occurrences, we estimate that 70% of these annotated genes are complete at their 5' end.     

Host genome surveillance for retrotransposons by transposon-derived proteins

Transposable elements and their remnants constitute a substantial fraction of eukaryotic genomes. Host genomes have evolved defence mechanisms, including chromatin modifications and RNA interference, to regulate transposable elements. Here we describe a genome surveillance mechanism for retrotransposons by transposase-derived centromeric protein CENP-B homologues of the fission yeast Schizosaccharomyces pombe. CENP-B homologues of S. pombe localize at and recruit histone deacetylases to silence Tf2 retrotransposons. CENP-Bs also repress solo long terminal repeats (LTRs) and LTR-associated genes. Tf2 elements are clustered into 'Tf' bodies, the organization of which depends on CENP-Bs that display discrete nuclear structures. Furthermore, CENP-Bs prevent an 'extinct' Tf1 retrotransposon from re-entering the host genome by blocking its recombination with extant Tf2, and silence and immobilize a Tf1 integrant that becomes sequestered into Tf bodies. Our results reveal a probable ancient retrotransposon surveillance pathway important for host genome integrity, and highlight potential conflicts between DNA transposons and retrotransposons, major transposable elements believed to have greatly moulded the evolution of genomes.     

Evolution of genes and genomes on the Drosophila phylogeny

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.     

Evolutionary transfer of the chloroplast tufA gene to the nucleus

Evolutionary gene transfer is a basic corollary of the now widely accepted endosymbiotic theory, which proposes that mitochondria and chloroplasts originated from once free-living eubacteria. The small organellar chromosomes are remnants of larger bacterial genomes, with most endosymbiont genes having been either transferred to the nucleus soon after endosymbiosis or lost entirely, with some being functionally replaced by pre-existing nuclear genes. Several lines of evidence indicate that relocation of some organelle genes could have been more recent. These include the abundance of non-functional organelle sequences of recent origin in nuclear DNA, successful artificial transfer of functional organelle genes to the nucleus, and several examples of recently lost organelle genes, although none of these is known to have been replaced by a nuclear homologue that is clearly of organellar ancestry. We present gene sequence and molecular phylogenetic evidence for the transfer of the chloroplast tufA gene to the nucleus in the green algal ancestor of land plants.     

Single gene circles in dinoflagellate chloroplast genomes.

Photosynthetic dinoflagellates are important aquatic primary producers and notorious causes of toxic 'red tides'. Typical dinoflagellate chloroplasts differ from all other plastids in having a combination of three envelope membranes and peridinin-chlorophyll a/c light-harvesting pigments. Despite evidence of a dinoflagellete satellite DNA containing chloroplast genes, previous attempts to obtain chloroplast gene sequences have been uniformly unsuccessful. Here we show that the dinoflagellate chloroplast DNA genome structure is unique. Complete sequences of chloroplast ribosomal RNA genes and seven chloroplast protein genes from the dinoflagellate Heterocapsa triquetra reveal that each is located alone on a separate minicircular chromosome: 'one gene-one circle'. The genes are the most divergent known from chloroplast genomes. Each circle has an unusual tripartite non-coding region (putative replicon origin), which is highly conserved among the nine circles through extensive gene conversion, but is very divergent between species. Several other dinoflagellate species have minicircular chloroplast genes, indicating that this type of genomic organization may have evolved in ancestral peridinean dinoflagellates. Phylogenetic analysis indicates that dinoflagellate chloroplasts are related to chromistan and red algal chloroplasts and supports their origin by secondary symbiogenesis.