Evolution and cellular function of monothiol glutaredoxins: involvement in iron-sulphur cluster assembly

A number of bacterial species, mostly proteobacteria, possess monothiol glutaredoxins homologous to the Saccharomyces cerevisiae mitochondrial protein Grx5, which is involved in iron-sulphur cluster synthesis. Phylogenetic profiling is used to predict that bacterial monothiol glutaredoxins also participate in the iron-sulphur cluster (ISC) assembly machinery, because their phylogenetic profiles are similar to the profiles of the bacterial homologues of yeast ISC proteins. High evolutionary co-occurrence is observed between the Grx5 homologues and the homologues of the Yah1 ferredoxin, the scaffold proteins Isa1 and Isa2, the frataxin protein Yfh1 and the Nfu1 protein. This suggests that a specific functional interaction exists between these ISC machinery proteins. Physical interaction analyses using low-definition protein docking predict the formation of strong and specific complexes between Grx5 and several components of the yeast ISC machinery. Two-hybrid analysis has confirmed the in vivo interaction between Grx5 and Isa1. Sequence comparison techniques and cladistics indicate that the other two monothiol glutaredoxins of S. cerevisiae, Grx3 and Grx4, have evolved from the fusion of a thioredoxin gene with a monothiol glutaredoxin gene early in the eukaryotic lineage, leading to differential functional specialization. While bacteria do not contain these chimaeric glutaredoxins, in many eukaryotic species Grx5 and Grx3/4-type monothiol glutaredoxins coexist in the cell.     

Evolution of domain combinations in protein kinases and its implications for functional diversity

Protein kinases phosphorylating Ser/Thr/Tyr residues in several cellular proteins exert tight control over their biological functions. They constitute the largest protein family in most eukaryotic species. Protein kinases classified based on sequence similarity in their catalytic domains, cluster into subfamilies, which share gross functional properties. Many protein kinases are associated or tethered covalently to domains that serve as adapter or regulatory modules, aiding substrate recruitment, specificity, and also serve as scaffolds. Hence the modular organisation of the protein kinases serves as guidelines to their functional and molecular properties. Analysis of genomic repertoires of protein kinases in eukaryotes have revealed wide spectrum of domain organisation across various subfamilies of kinases. Occurrence of organism-specific novel domain combinations suggests functional diversity achieved by protein kinases in order to regulate variety of biological processes. In addition, domain architecture of protein kinases revealed existence of hybrid protein kinase subfamilies and their emerging roles in the signaling of eukaryotic organisms. In this review we discuss the repertoire of non-kinase domains tethered to multi-domain kinases in the metazoans. Similarities and differences in the domain architectures of protein kinases in these organisms indicate conserved and unique features that are critical to functional specialization.     

Evolution at the subgene level: domain rearrangements in the Drosophila phylogeny

Although the possibility of gene evolution by domain rearrangements has long been appreciated, current methods for reconstructing and systematically analyzing gene family evolution are limited to events such as duplication, loss, and sometimes, horizontal transfer. However, within the Drosophila clade, we find domain rearrangements occur in 35.9% of gene families, and thus, any comprehensive study of gene evolution in these species will need to account for such events. Here, we present a new computational model and algorithm for reconstructing gene evolution at the domain level. We develop a method for detecting homologous domains between genes and present a phylogenetic algorithm for reconstructing maximum parsimony evolutionary histories that include domain generation, duplication, loss, merge (fusion), and split (fission) events. Using this method, we find that genes involved in fusion and fission are enriched in signaling and development, suggesting that domain rearrangements and reuse may be crucial in these processes. We also find that fusion is more abundant than fission, and that fusion and fission events occur predominantly alongside duplication, with 92.5% and 34.3% of fusion and fission events retaining ancestral architectures in the duplicated copies. We provide a catalog of ～9,000 genes that undergo domain rearrangement across nine sequenced species, along with possible mechanisms for their formation. These results dramatically expand on evolution at the subgene level and offer several insights into how new genes and functions arise between species.     

Evolution of the CDKN1C-KCNQ1 imprinted domain

Background  

Genomic imprinting occurs in both marsupial and eutherian mammals. The CDKN1C and IGF2 genes are both imprinted and syntenic in the mouse and human, but in marsupials only IGF2 is imprinted. This study examines the evolution of features that, in eutherians, regulate CDKN1C imprinting.     

Evolution of multi-enzyme complexes: the case of tryptophan synthase

The prototypical tryptophan synthase is a stable heterotetrameric alpha-betabeta-alpha complex. The constituting TrpA and TrpB1 subunits, which are encoded by neighboring genes in the trp operon, activate each other in a bi-directional manner. Recently, a novel class of TrpB2 proteins has been identified, whose members contain additional amino acids that might sterically prevent complex formation with TrpA. To test this hypothesis, we characterized the TrpA and TrpB proteins from Sulfolobus solfataricus. This hyperthermophilic archaeon does not contain a TrpB1 protein but instead contains two TrpB2 homologues that are encoded within (TrpB2i) and outside (TrpB2o) the trp operon. We find that TrpB2i and TrpA form a weak and transient complex during catalysis, with a uni-directional activation of TrpA by TrpB2i. In contrast, TrpB2o and TrpA do not form a detectable complex. These results suggest a model for the evolution of the tryptophan synthase in which TrpB2o, TrpB2i, and TrpB1 reflect the stepwise increase of TrpB affinity for TrpA and the refinement of functional subunit interaction, concomitant with the co-localization of the encoding genes in the trp operon.     

Evolution of domain promiscuity in eukaryotic genomes--a perspective from the inferred ancestral domain architectures

Most eukaryotic proteins are composed of two or more domains. These assemble in a modular manner to create new proteins usually by the acquisition of one or more domains to an existing protein. Promiscuous domains which are found embedded in a variety of proteins and co-exist with many other domains are of particular interest and were shown to have roles in signaling pathways and mediating network communication. The evolution of domain promiscuity is still an open problem, mostly due to the lack of sequenced ancestral genomes. Here we use inferred domain architectures of ancestral genomes to trace the evolution of domain promiscuity in eukaryotic genomes. We find an increase in average promiscuity along many branches of the eukaryotic tree. Moreover, domain promiscuity can proceed at almost a steady rate over long evolutionary time or exhibit lineage-specific acceleration. We also observe that many signaling and regulatory domains gained domain promiscuity around the Bilateria divergence. In addition we show that those domains that played a role in the creation of two body axes and existed before the divergence of the bilaterians from fungi/metazoan achieve a boost in their promiscuities during the bilaterian evolution.     

Evolution of prokaryotic homologues of the eukaryotic SEFIR protein domain

SEF/IL17 receptor (SEFIR) domains are mainly found in IL17 receptors (IL17Rs) and their adaptor proteins CIKS (connection to IKK and SAPK/JNK), which exert a host defense role in numbers of infectious diseases and promote inflammatory pathology in autoimmunity. Exploring the evolutionary pathway of SEFIR domains will provide further insight into their functions. Here, we have identified 84 SEFIR domain-containing proteins from more than 1400 prokaryotic genomes. As most SEFIR domain-containing bacterial genomes possess a single SEFIR encoding gene and the SEFIR protein domain forms homodimeric complexes like the Toll/IL1 receptor (TIR) domain, the single bacterial SEFIR proteins may receive binding partners from other organisms. Through comparative and phylogenetic sequence analyses, we show that bacterial SEFIR domain is more similar to that of vertebrate CIKS than IL17R, and it possibly emerges via a lateral gene transfer (LGT) from animals. In addition, our secondary and three-dimensional structural predictions of SEFIR domains reveal that human and pathogenic bacterial SEFIR domains share similar structural and electrostatic features. Our findings provide important clues for further experimental researches on determining the functions of SEFIR proteins in pathogenic prokaryotes.     

Evolution: reducible complexity -- the case for bacterial flagella

A recent paper, which will surely figure centrally in the debate between evolutionists and Intelligent Design creationists, proposes a (perhaps too simple) scheme for the evolution of bacterial flagella.     

Evolution by acquisition: the case for horizontal gene transfers

One of the most debated questions in the field of molecular evolution is the possible role of horizontal transfer in evolution. Of all the claims that have been made over the years, those reporting transfers between eukaryotes and prokaryotes are the most controversial. Here we present the cases for and against several such possible gene acquisitions.     

基于地形因子的三峡库区腹地耕地演变——以草堂溪流域为例

以1990、2000、2004和2007年4期遥感影像数据和1∶5万的DEM数据为数据源,利用ArcGIS 9.3空间分析功能和Fragstas 3.3景观格局分析功能对库区腹地耕地演变进行了研究.首先建立草堂溪流域耕地数据库以及高程、坡度和地形位指数图,然后将高程、坡度和地形位梯度分别与耕地数据进行图层运算,提取坡耕地的面积,探讨不同地形下耕地的分布特征.结果表明:耕地在各地形因素上的分布表现为15° ～35°坡度带、500～1000 m高程级别、东南坡及南坡以及中高地形上.1990-2007年,研究区耕地在面积和空间格局上均发生很大的变化,随地形梯度的增大,4个时期耕地分布面积随地形位指数的增大表现为先升后降;聚集度减少特别显著的主要集中在第4(1.2～1.5)和5(1.5 ～2.0)两个地形梯度带,即中高地形位的耕地之间聚集程度降低,破碎程度加剧,生态环境好转.     

The repertoire of protein kinases encoded in the draft version of the human genome: atypical variations and uncommon domain combinations

Background

Phosphorylation by protein kinases is central to cellular signal transduction. Abnormal functioning of kinases has been implicated in developmental disorders and malignancies. Their activity is regulated by second messengers and by the binding of associated domains, which are also influential in translocating the catalytic component to their substrate sites, in mediating interaction with other proteins and carrying out their biological roles.

Result

Using sensitive profile-search methods and manual analysis, the human genome has been surveyed for protein kinases. A set of 448 sequences, which show significant similarity to protein kinases and contain the critical residues essential for kinase function, have been selected for an analysis of domain combinations after classifying the kinase domains into subfamilies. The unusual domain combinations in particular kinases suggest their involvement in ubiquitination pathways and alternative modes of regulation for mitogen-activated protein kinase kinases (MAPKKs) and cyclin-dependent kinase (CDK)-like kinases. Previously unexplored kinases have been implicated in osteoblast differentiation and embryonic development on the basis of homology with kinases of known functions from other organisms. Kinases potentially unique to vertebrates are involved in highly evolved processes such as apoptosis, protein translation and tyrosine kinase signaling. In addition to coevolution with the kinase domain, duplication and recruitment of non-catalytic domains is apparent in signaling domains such as the PH, DAG-PE, SH2 and SH3 domains.

Conclusions

Expansion of the functional repertoire and possible existence of alternative modes of regulation of certain kinases is suggested by their uncommon domain combinations. Experimental verification of the predicted implications of these kinases could enhance our understanding of their biological roles.

     

基于全基因组结构域信息的进化树构建

重建生物进化树一直以来都是进化生物学家的梦想。大量物种全基因组的测序使得我们可以从全基因组水平上构建进化树,来研究各个物种之间的进化关系。本文采用2种统计方法和3种距离计算方法,在全基因组水平上建立基于蛋白质结构的进化树。选取93个物种的全基因组作为分析对象,涵盖了3个超界:真核生物,细菌和古细菌。而结果也正确地将这些物种分为三个大类,每个大分支内部的物种聚类情况也基本和这些物种的形态学分类相吻合。并将这些方法的聚类结果与物种分类的结果相比较,得出丰度的统计方法和基于两向量夹角的距离计算方法这种组合在构建进化树上比其他组合更好。     

Evolution of invertebrate nervous systems: the Chaetognatha as a case study

Harzsch, S. and Wanninger, A. 2010. Evolution of invertebrate nervous systems: the Chaetognatha as a case study. —Acta Zoologica (Stockholm) 91 : 35–43 Although recent molecular studies indicate that Chaetognatha may be one of the earliest Bilaterian offshoots, the phylogenetic position of this taxon still is a matter of ongoing debate. In this contribution, we review recent attempts to contribute phylogenetic information on the Chaetognatha by analysing structure and development of their nervous system (neurophylogeny). Analysing this group of organisms also has a major impact on our understanding of nervous system evolution in Bilateria. We review recent evidence from this field and suggest that Urbilateria already was equipped with the genetic toolkit required to build a complex, concentrated central nervous system (CNS), although this was not expressed phenotypically so that Urbilateria was equipped with a nerve plexus and not a CNS. This implies that in the deep metazoan nodes, concentration of the ancestral plexus occurred twice independently, namely once after the protostome–deuterostome split on the branch leading to the protostomes (resulting in a ventrally positioned nerve cord) and once along the chordate line (with a dorsal nerve cord).     

Characterization of domain-peptide interaction interface: a case study on the amphiphysin-1 SH3 domain

Many important protein-protein interactions are mediated by peptide recognition modular domains, such as the Src homology 3 (SH3), SH2, PDZ, and WW domains. Characterizing the interaction interface of domain-peptide complexes and predicting binding specificity for modular domains are critical for deciphering protein-protein interaction networks. Here, we propose the use of an energetic decomposition analysis to characterize domain-peptide interactions and the molecular interaction energy components (MIECs), including van der Waals, electrostatic, and desolvation energy between residue pairs on the binding interface. We show a proof-of-concept study on the amphiphysin-1 SH3 domain interacting with its peptide ligands. The structures of the human amphiphysin-1 SH3 domain complexed with 884 peptides were first modeled using virtual mutagenesis and optimized by molecular mechanics (MM) minimization. Next, the MIECs between domain and peptide residues were computed using the MM/generalized Born decomposition analysis. We conducted two types of statistical analyses on the MIECs to demonstrate their usefulness for predicting binding affinities of peptides and for classifying peptides into binder and non-binder categories. First, combining partial least squares analysis and genetic algorithm, we fitted linear regression models between the MIECs and the peptide binding affinities on the training data set. These models were then used to predict binding affinities for peptides in the test data set; the predicted values have a correlation coefficient of 0.81 and an unsigned mean error of 0.39 compared with the experimentally measured ones. The partial least squares-genetic algorithm analysis on the MIECs revealed the critical interactions for the binding specificity of the amphiphysin-1 SH3 domain. Next, a support vector machine (SVM) was employed to build classification models based on the MIECs of peptides in the training set. A rigorous training-validation procedure was used to assess the performances of different kernel functions in SVM and different combinations of the MIECs. The best SVM classifier gave satisfactory predictions for the test set, indicated by average prediction accuracy rates of 78% and 91% for the binding and non-binding peptides, respectively. We also showed that the performance of our approach on both binding affinity prediction and binder/non-binder classification was superior to the performances of the conventional MM/Poisson-Boltzmann solvent-accessible surface area and MM/generalized Born solvent-accessible surface area calculations. Our study demonstrates that the analysis of the MIECs between peptides and the SH3 domain can successfully characterize the binding interface, and it provides a framework to derive integrated prediction models for different domain-peptide systems.     

Evolution of genes,evolution of species: the case of aminoacyl-tRNA synthetases

All of the aminoacyl-tRNA synthetase (aaRS) sequences currently available in the data banks have been subjected to a systematic analysis aimed at finding gene duplications, genetic recombinations, and horizontal transfers. Evidence is provided for the occurrence (or probable occurrence) of such phenomena within this class of enzymes. In particular, it is suggested that the monomeric PheRS from the yeast mitochondrion is a chimera of the alpha and beta chains of the standard tetrameric protein. In addition, it is proposed that the dimeric and tetrameric forms of GlyRS are the result of a double and independent acquisition of the same specificity within two different subclasses of aaRS. The phylogenetic reconstructions of the evolutionary histories of the genes encoding aaRS are shown to be extremely diverse. While large segments of the population are consistent with the broad grouping into the three Woesian domains, some phylogenetic reconstructions do not place the Archae and the Eucarya as sister groups but, rather, show a gram-negative bacteria/eukaryote clustering. In addition, many individual genes pose difficulties that preclude any simple evolutionary scheme. Thus, aaRS's are clearly a paradigm of F. Jacob's "odd jobs of evolution" but, on the whole, do not call into question the evolutionary scenario originally proposed by Woese and subsequently refined by others.     

Evolution of the fibronectin gene. Exon structure of cell attachment domain

Genomic DNA coding for human fibronectin was identified from a human genomic library by screening with a cDNA clone that specifies the cell attachment domain in human fibronectin. Two clones which together provided more than 22 kilobase pairs of the fibronectin gene were isolated. The exons in this region correspond to approximately 40% of the coding region in the fibronectin gene. They code for the middle region of the polypeptide which consists of homologous repeating segments of about 90 amino acids called type III homologies. Nucleotide sequence of the portion of the gene corresponding to the cell attachment domain showed that the Arg-Gly-Asp-Ser cell attachment site is encoded within a 165-base pair exon. This exon, together with a 117-base pair exon codes for a homology unit. Analysis of the exon/intron organization in some of the neighboring homology units indicated a similar 2-exon structure. An exception to this pattern is that a single large exon codes for a type III homology unit that, due to alternative mRNA splicing, exists in some but not all fibronectin polypeptides. The introns separating the coding sequences for the type III homology units are located in conserved positions whereas the introns that interrupt the coding sequence within the units are in a variable position generating variations in the size of the homologous exons. This exon/intron organization suggests that the type III homology region of the fibronectin gene has evolved by a series of gene duplications of a primordial gene consisting of two exons. Specification of one of these homology units to the cell attachment domain has occurred within this exon/intron arrangement.     

Evolution in knockout conflicts: The fixed strategy case

A group of individuals resolve their disputes by a knockout tournament. In each round of the tournament, the remaining contestants form pairs which compete, the winners progressing to the next round and the losers being eliminated. The payoff received depends upon how far the player has progressed and a cost is incurred only when it is defeated. We only consider strategies in which individuals are constrained to adopt a fixed play throughout the successive rounds. The case where individuals can vary their choice of behaviour from round to round will be treated elsewhere. The complexity of the system is investigated and illustrated both by special cases and numerical examples. M. Broom is also a member of the Centre for the Study of Evolution at the University of Sussex.     

A hypothetical model for the peptide binding domain of hsp70 based on the peptide binding domain of HLA

The sequences of the peptide binding domains of 33 70 kd heat shock proteins (hsp70) have been aligned and a consensus secondary structure has been deduced. Individual members showed no significant deviation from the consensus, which showed a beta 4 alpha motif repeated twice, followed by two further helices and a terminus rich in Pro and Gly. The repeated motif could be aligned with the secondary structure of the functionally equivalent peptide binding domain of human leucocyte antigen (HLA) class I maintaining equivalent residues in structurally important positions in the two families and a model was built based on this alignment. The interaction of this domain with the ATP domain is considered. The overall model is shown to be consistent with the properties of products of chymotryptic cleavage.