The family of metazoan metal-independent {beta}-galactoside-binding lectins: structure, function and molecular evolution

Animal metal-independent ß-galactoside-binding lectinswere initially found in vertebrates, but they have recentlybeen isolated from much lower invertebrates, such as nematodeand sponge, as well. Further, an eosinophilic lysophospholipaseassociated with various inflammatory reactions was very recentlyfound to be a new member of this protein family. It appearsthat ß-galactoside-binding lectins and some non-lectinproteins form a superfamily whose members are widely distributedfrom vertebrates to invertebrates. From the viewpoints of proteinarchitecture, the superfamily members can be subdivided intothree types; i.e. ‘proto type’ (the relatively well-studied14 kDa lectins), ‘chimera type’ (29–35 kDalectins also known as     

The Dlx genes as clues to vertebrate genomics and craniofacial evolution

The group of Dlx genes belongs to the homeobox-containing superfamily, and its members are involved in various morphogenetic processes. In vertebrate genomes, Dlx genes exist as multiple paralogues generated by tandem duplication followed by whole genome duplications. In this review, we provide an overview of the Dlx gene phylogeny with an emphasis on the chordate lineage. Referring to the Dlx gene repertoire, we discuss the establishment and conservation of the nested expression patterns of the Dlx genes in craniofacial development. Despite the accumulating genomic sequence resources in diverse vertebrates, embryological analyses of Dlx gene expression and function remain limited in terms of species diversity. By supplementing our original analysis of shark embryos with previous data from other osteichthyans, such as mice and zebrafish, we support the previous speculation that the nested Dlx expression in the pharyngeal arch is likely a shared feature among all the extant jawed vertebrates. Here, we highlight several hitherto unaddressed issues regarding the evolution and function of Dlx genes, with special reference to the craniofacial development of vertebrates.     

Comparative study of the <Emphasis Type="Italic">P2X</Emphasis> gene family in animals and plants

P2X receptors are ligand-gated ion channels that can bind with the adenosine triphosphate (ATP) and have diverse functional roles in neuropathic pain, inflammation, special sense, and so on. In this study, 180 putative P2X genes, including 176 members in 32 animal species and 4 members in 3 species of lower plants, were identified. These genes were divided into 13 groups, including 7 groups in vertebrates and 6 groups in invertebrates and lower plants, through phylogenetic analysis. Their gene organization and motif composition are conserved in most predicted P2X members, while group-specific features were also found. Moreover, synteny relationships of the putative P2X genes in vertebrates are conserved while simultaneously experiencing a series of gene insertion, inversion, and transposition. Recombination signals were detected in almost all of the vertebrates and invertebrates, suggesting that intragenic recombination may play a significant role in the evolution of P2X genes. Selection analysis also identified some positively selected sites that acted on the evolution of most of the predicted P2X proteins. The phenomenon of alternative splicing occurred commonly in the putative P2X genes of vertebrates. This article explored in depth the evolutional relationship among different subtypes of P2X genes in animal and plants and might serve as a solid foundation for deciphering their functions in further studies.     

A genomewide analysis of genes for the heat shock protein 70 chaperone system in the ascidian Ciona intestinalis

Molecular chaperones play crucial roles in various aspects of the biogenesis and maintenance of proteins in the cell. The heat shock protein 70 (HSP70) chaperone system, in which HSP70 proteins act as chaperones, is one of the major molecular chaperone systems conserved among a variety of organisms. To shed light on the evolutionary history of the constituents of the chordate HSP70 chaperone system and to identify all of the components of the HSP70 chaperone system in ascidians, we carried out a comprehensive survey for HSP70s and their cochaperones in the genome of Ciona intestinalis. We characterized all members of the Ciona HSP70 superfamily, J-proteins, BAG family, and some other types of cochaperones. The Ciona genome contains 8 members of the HSP70 superfamily, all of which have human and protostome counterparts. Members of the STCH subfamily of the HSP70 family and members of the HSPA14 subfamily of the HSP110 family are conserved between humans and protostomes but were not found in Ciona. The Ciona genome encodes 36 J-proteins, 32 of which belong to groups conserved in humans and protostomes. Three proteins seem to be unique to Ciona. J-proteins of the RBJ group are conserved between humans and Ciona but were not found in protostomes, whereas J-proteins of the DNAJC14, ZCSL3, FLJ13236, and C21orf55 groups are conserved between humans and protostomes but were not found in Ciona. J-proteins of the sacsin group seem to be specific to vertebrates. There is also a J-like protein without a conserved HPD tripeptide motif in the Ciona genome. The Ciona genome encodes 3 types of BAG family proteins, all of which have human and protostome counterparts (BAG1, BAG3, and BAT3). BAG2 group is conserved between humans and protostomes but was not found in Ciona, and BAG4 and BAG5 groups seem to be specific to vertebrates. Members for SIL1, UBQLN, UBADC1, TIMM44, GRPEL, and Magmas groups, which are conserved between humans and protostomes, were also found in Ciona. No Ciona member was retrieved for HSPBP1 group, which is conserved between humans and protostomes. For several groups of the HSP70 superfamily, J-proteins, and other types of cochaperones, multiple members in humans are represented by a single counterpart in Ciona. These results show that genes of the HSP70 chaperone system can be distinguished into groups that are shared by vertebrates, Ciona, and protostomes, ones shared by vertebrates and protostomes, ones shared by vertebrates and Ciona, and ones specific to vertebrates, Ciona, or protostomes. These results also demonstrate that the components of the HSP70 chaperone system in Ciona are similar to but simpler than those in humans and suggest that changes of the genome in the lineage leading to humans after the separation from that leading to Ciona increased the number and diversity of members of the HSP70 chaperone system. Changes of the genome in the lineage leading to Ciona also seem to have made the HSP70 chaperone system in this species slightly simpler than that in the common ancestor of humans and Ciona.     

The carboxylesterase/cholinesterase gene family in invertebrate deuterostomes

Carboxylesterase/cholinesterase family members are responsible for controlling the nerve impulse, detoxification and various developmental functions, and are a major target of pesticides and chemical warfare agents. Comparative structural analysis of these enzymes is thus important. The invertebrate deuterostomes (phyla Echinodermata and Hemichordata and subphyla Urochordata and Cephalochordata) lie in the transition zone between invertebrates and vertebrates, and are thus of interest to the study of evolution. Here we have investigated the carboxylesterase/cholinesterase gene family in the sequenced genomes of Strongylocentrotus purpuratus (Echinodermata), Saccoglossus kowalevskii (Hemichordata), Ciona intestinalis (Urochordata) and Branchiostoma floridae (Cephalochordata), using sequence analysis of the catalytic apparatus and oligomerisation domains, and phylogenetic analysis. All four genomes show blurring of structural boundaries between cholinesterases and carboxylesterases, with many intermediate enzymes. Non-enzymatic proteins are well represented. The Saccoglossus and Branchiostoma genomes show evidence of extensive gene duplication and retention. There is also evidence of domain shuffling, resulting in multidomain proteins consisting either of multiple carboxylesterase domains, or of carboxylesterase/cholinesterase domains linked to other domains, including RING finger, chitin-binding, immunoglobulin, fibronectin type 3, CUB, cysteine-rich-Frizzled, caspase activation and 7tm-1, amongst others. Such gene duplication and domain shuffling in the carboxylesterase/cholinesterase family appears to be unique to the invertebrate deuterostomes, and we hypothesise that these factors may have contributed to the evolution of the morphological complexity, particularly of the nervous system and neural crest, of the vertebrates.     

Superfamily active site templates

We show that three-dimensional signatures consisting of only a few functionally important residues can be diagnostic of membership in superfamilies of enzymes. Using the enolase superfamily as a model system, we demonstrate that such a signature, or template, can identify superfamily members in structural databases with high sensitivity and specificity. This is remarkable because superfamilies can be highly diverse, with members catalyzing many different overall reactions; the unifying principle can be a conserved partial reaction or chemical capability. Our definition of a superfamily thus hinges on the disposition of residues involved in a conserved function, rather than on fold similarity alone. A clear advantage of basing structure searches on such active site templates rather than on fold similarity is the specificity with which superfamilies with distinct functional characteristics can be identified within a large set of proteins with the same fold, such as the (beta/alpha)8 barrels. Preliminary results are presented for an additional group of enzymes with a different fold, the haloacid dehalogenase superfamily, suggesting that this approach may be generally useful for assigning reading frames of unknown function to specific superfamilies and thereby allowing inference of some of their functional properties.     

The C-type lectin-like domain superfamily

The superfamily of proteins containing C-type lectin-like domains (CTLDs) is a large group of extracellular Metazoan proteins with diverse functions. The CTLD structure has a characteristic double-loop ('loop-in-a-loop') stabilized by two highly conserved disulfide bridges located at the bases of the loops, as well as a set of conserved hydrophobic and polar interactions. The second loop, called the long loop region, is structurally and evolutionarily flexible, and is involved in Ca2+-dependent carbohydrate binding and interaction with other ligands. This loop is completely absent in a subset of CTLDs, which we refer to as compact CTLDs; these include the Link/PTR domain and bacterial CTLDs. CTLD-containing proteins (CTLDcps) were originally classified into seven groups based on their overall domain structure. Analyses of the superfamily representation in several completely sequenced genomes have added 10 new groups to the classification, and shown that it is applicable only to vertebrate CTLDcps; despite the abundance of CTLDcps in the invertebrate genomes studied, the domain architectures of these proteins do not match those of the vertebrate groups. Ca2+-dependent carbohydrate binding is the most common CTLD function in vertebrates, and apparently the ancestral one, as suggested by the many humoral defense CTLDcps characterized in insects and other invertebrates. However, many CTLDs have evolved to specifically recognize protein, lipid and inorganic ligands, including the vertebrate clade-specific snake venoms, and fish antifreeze and bird egg-shell proteins. Recent studies highlight the functional versatility of this protein superfamily and the CTLD scaffold, and suggest further interesting discoveries have yet to be made.     

A survey of integral α-helical membrane proteins

Membrane proteins serve as cellular gatekeepers, regulators, and sensors. Prior studies have explored the functional breadth and evolution of proteins and families of particular interest, such as the diversity of transport-associated membrane protein families in prokaryotes and eukaryotes, the composition of integral membrane proteins, and family classification of all human G-protein coupled receptors. However, a comprehensive analysis of the content and evolutionary associations between membrane proteins and families in a diverse set of genomes is lacking. Here, a membrane protein annotation pipeline was developed to define the integral membrane genome and associations between 21,379 proteins from 34 genomes; most, but not all of these proteins belong to 598 defined families. The pipeline was used to provide target input for a structural genomics project that successfully cloned, expressed, and purified 61 of our first 96 selected targets in yeast. Furthermore, the methodology was applied (1) to explore the evolutionary history of the substrate-binding transmembrane domains of the human ABC transporter superfamily, (2) to identify the multidrug resistance-associated membrane proteins in whole genomes, and (3) to identify putative new membrane protein families.     

基因倍增和脊椎动物起源

有机体基因复制导致基因复杂性增加及其和脊椎动物起源的关系已经成为进化生物学研究的热点。20世纪70年代由Ohno提出后经Holland等修正的原始脊索动物经两轮基因组复制产生脊椎动物的假设目前已被广泛接受。脊椎动物起源和进化过程中发生过两轮基因组复制的主要证据有三点：（1）据估计脊椎动物基因组内编码基因数目大约相当于果蝇、海鞘等无脊椎动物的4倍;原口动物如果蝇和后口动物如头索动物文昌鱼的基因组大都只有单拷贝的基因,而脊椎动物的基因组则通常有4个同属于一个家族的基因。（2）无脊椎动物如节肢动物、海胆和头索动物文昌鱼都只有一个Hox基因簇,而脊椎动物除鱼类外,有7个具有Hox基因簇,其余都具有4个Hox基因簇。（3）基因作图证明,不但在鱼类和哺乳动物染色体广大片段上基因顺序相似,而且有证据显示哺乳动物基因组不同染色体之间存在相似性。据认为第一次基因倍增发生在脊椎动物与头索动物分开之后,第二次基因倍增发生在有颌类脊椎动物和无颌类脊椎动物分开以后。但是,基因是逐个发生倍增,还是通过基因组内某些DNA片段抑或整个基因组的加倍而实现的,目前还颇有争议。     

Using paleogenomics to study the evolution of gene families: origin and duplication history of the relaxin family hormones and their receptors

Recent progress in the analysis of whole genome sequencing data has resulted in the emergence of paleogenomics, a field devoted to the reconstruction of ancestral genomes. Ancestral karyotype reconstructions have been used primarily to illustrate the dynamic nature of genome evolution. In this paper, we demonstrate how they can also be used to study individual gene families by examining the evolutionary history of relaxin hormones (RLN/INSL) and relaxin family peptide receptors (RXFP). Relaxin family hormones are members of the insulin superfamily, and are implicated in the regulation of a variety of primarily reproductive and neuroendocrine processes. Their receptors are G-protein coupled receptors (GPCR's) and include members of two distinct evolutionary groups, an unusual characteristic. Although several studies have tried to elucidate the origins of the relaxin peptide family, the evolutionary origin of their receptors and the mechanisms driving the diversification of the RLN/INSL-RXFP signaling systems in non-placental vertebrates has remained elusive. Here we show that the numerous vertebrate RLN/INSL and RXFP genes are products of an ancestral receptor-ligand system that originally consisted of three genes, two of which apparently trace their origins to invertebrates. Subsequently, diversification of the system was driven primarily by whole genome duplications (WGD, 2R and 3R) followed by almost complete retention of the ligand duplicates in most vertebrates but massive loss of receptor genes in tetrapods. Interestingly, the majority of 3R duplicates retained in teleosts are potentially involved in neuroendocrine regulation. Furthermore, we infer that the ancestral AncRxfp3/4 receptor may have been syntenically linked to the AncRln-like ligand in the pre-2R genome, and show that syntenic linkages among ligands and receptors have changed dynamically in different lineages. This study ultimately shows the broad utility, with some caveats, of incorporating paleogenomics data into understanding the evolution of gene families.     

Evolutionary history of the vertebrate mitogen activated protein kinases family

Background

The mitogen activated protein kinases (MAPK) family pathway is implicated in diverse cellular processes and pathways essential to most organisms. Its evolution is conserved throughout the eukaryotic kingdoms. However, the detailed evolutionary history of the vertebrate MAPK family is largely unclear.

Methodology/Principal Findings

The MAPK family members were collected from literatures or by searching the genomes of several vertebrates and invertebrates with the known MAPK sequences as queries. We found that vertebrates had significantly more MAPK family members than invertebrates, and the vertebrate MAPK family originated from 3 progenitors, suggesting that a burst of gene duplication events had occurred after the divergence of vertebrates from invertebrates. Conservation of evolutionary synteny was observed in the vertebrate MAPK subfamilies 4, 6, 7, and 11 to 14. Based on synteny and phylogenetic relationships, MAPK12 appeared to have arisen from a tandem duplication of MAPK11 and the MAPK13-MAPK14 gene unit was from a segmental duplication of the MAPK11-MAPK12 gene unit. Adaptive evolution analyses reveal that purifying selection drove the evolution of MAPK family, implying strong functional constraints of MAPK genes. Intriguingly, however, intron losses were specifically observed in the MAPK4 and MAPK7 genes, but not in their flanking genes, during the evolution from teleosts to amphibians and mammals. The specific occurrence of intron losses in the MAPK4 and MAPK7 subfamilies might be associated with adaptive evolution of the vertebrates by enhancing the gene expression level of both MAPK genes.

Conclusions/Significance

These results provide valuable insight into the evolutionary history of the vertebrate MAPK family.     

Phylogenetic analysis reveals stowaway-like elements may represent a fourth family of the IS630-Tc1-mariner superfamily.

The genomes of plants, like virtually all other eukaryotic organisms, harbor a diverse array of mobile elements, or transposons. In terms of numbers, the predominant type of transposons in many plants is the miniature inverted-repeat transposable element (MITE). There are three archetypal MITEs, known as Tourist, Stowaway, and Emigrant, each of which can be defined by a specific terminal inverted-repeat (TIR) sequence signature. Although their presence was known for over a decade, only recently have open reading frames (ORFs) been identified that correspond to putative transposases for each of the archetypes. We have identified two Stowaway elements that encode a putative transposase and are similar to members of the previously characterized IS630-Tc1-mariner superfamily. In this report, we provide a high-resolution phylogenetic analysis of the evolutionary relationship between Stowaway, Emigrant, and members of the IS630-Tc1-mariner superfamily. We show that although Emigrant is closely related to the pogo-like family of elements, Stowaway may represent a novel family. Integration of our results with previously published data leads to the conclusion that the three main types of MITEs have different evolutionary histories despite similarity in structure.     

PIF- and Pong-like transposable elements: distribution, evolution and relationship with Tourist-like miniature inverted-repeat transposable elements

Miniature inverted-repeat transposable elements (MITEs) are short, nonautonomous DNA elements that are widespread and abundant in plant genomes. Most of the hundreds of thousands of MITEs identified to date have been divided into two major groups on the basis of shared structural and sequence characteristics: Tourist-like and Stowaway-like. Since MITEs have no coding capacity, they must rely on transposases encoded by other elements. Two active transposons, the maize P Instability Factor (PIF) and the rice Pong element, have recently been implicated as sources of transposase for Tourist-like MITEs. Here we report that PIF- and Pong-like elements are widespread, diverse, and abundant in eukaryotes with hundreds of element-associated transposases found in a variety of plant, animal, and fungal genomes. The availability of virtually the entire rice genome sequence facilitated the identification of all the PIF/Pong-like elements in this organism and permitted a comprehensive analysis of their relationship with Tourist-like MITEs. Taken together, our results indicate that PIF and Pong are founding members of a large eukaryotic transposon superfamily and that members of this superfamily are responsible for the origin and amplification of Tourist-like MITEs.     

Identification of new homologs of PD-(D/E)XK nucleases by support vector machines trained on data derived from profile-profile alignments

PD-(D/E)XK nucleases, initially represented by only Type II restriction enzymes, now comprise a large and extremely diverse superfamily of proteins. They participate in many different nucleic acids transactions including DNA degradation, recombination, repair and RNA processing. Different PD-(D/E)XK families, although sharing a structurally conserved core, typically display little or no detectable sequence similarity except for the active site motifs. This makes the identification of new superfamily members using standard homology search techniques challenging. To tackle this problem, we developed a method for the detection of PD-(D/E)XK families based on the binary classification of profile-profile alignments using support vector machines (SVMs). Using a number of both superfamily-specific and general features, SVMs were trained to identify true positive alignments of PD-(D/E)XK representatives. With this method we identified several PFAM families of uncharacterized proteins as putative new members of the PD-(D/E)XK superfamily. In addition, we assigned several unclassified restriction enzymes to the PD-(D/E)XK type. Results show that the new method is able to make confident assignments even for alignments that have statistically insignificant scores. We also implemented the method as a freely accessible web server at http://www.ibt.lt/bioinformatics/software/pdexk/.     

Tc8, a Tourist-like transposon in Caenorhabditis elegans.

Members of the Tourist family of miniature inverted-repeat transposable elements (MITEs) are very abundant among a wide variety of plants, are frequently found associated with normal plant genes, and thus are thought to be important players in the organization and evolution of plant genomes. In Arabidopsis, the recent discovery of a Tourist member harboring a putative transposase has shed new light on the mobility and evolution of MITEs. Here, we analyze a family of Tourist transposons endogenous to the genome of the nematode Caenorhabditis elegans (Bristol N2). One member of this large family is 7568 bp in length, harbors an ORF similar to the putative Tourist transposase from Arabidopsis, and is related to the IS5 family of bacterial insertion sequences (IS). Using database searches, we found expressed sequence tags (ESTs) similar to the putative Tourist transposases in plants, insects, and vertebrates. Taken together, our data suggest that Tourist-like and IS5-like transposons form a superfamily of potentially active elements ubiquitous to prokaryotic and eukaryotic genomes.