HSA4 and GGA4: remarkable conservation despite 300-Myr divergence

The chicken (GGA) and human (HSA) genomes diverged around 300-350 Myr ago. Due to this large phylogenetic distance, significant synteny conservation has not been anticipated between the genomes of the two species. However, Zoo-FISH with HSA4 chromosome-specific paint on chicken metaphase chromosomes shows that the human chromosome corresponds largely to the GGA4cen-->q26 region. Comparative gene mapping data in the two species, though limited, provide strong support for these observations. The findings, together with the very recently published data on HSA9-GGAZ and HSA12-GGA1, show that some large chromosomal segments share conserved synteny in the two species. These syntenies are considerably disrupted in the mouse. This makes us believe that despite very early divergence, parts of the human and chicken genomes are more conserved than those of human and mouse, which radiated only 100-120 Myr ago. Moreover, the HSA4-GGA4q correspondence points to a "candidate" chromosome from the karyotype of a mammal-bird ancestor. The findings are thus a small but important step toward understanding the evolution of the two genomes.     

Evolutionary conservation of P-selectin glycoprotein ligand-1 primary structure and function

Background  

P-selectin glycoprotein ligand-1 (PSGL-1) plays a critical role in recruiting leukocytes in inflammatory lesions by mediating leukocyte rolling on selectins. Core-2 O-glycosylation of a N -terminal threonine and sulfation of at least one tyrosine residue of PSGL-1 are required for L- and P-selectin binding. Little information is available on the intra- and inter-species evolution of PSGL-1 primary structure. In addition, the evolutionary conservation of selectin binding site on PSGL-1 has not been previously examined in detail. Therefore, we performed multiple sequence alignment of PSGL-1 amino acid sequences of 14 mammals (human, chimpanzee, rhesus monkey, bovine, pig, rat, tree-shrew, bushbaby, mouse, bat, horse, cat, sheep and dog) and examined mammalian PSGL-1 interactions with human selectins.     

三叶肽：从结构到功能

三叶结构域是一段由38－39个氨基酸组成的多肽序列,其中包含6个高度保守的半胱氨酸残基,这6个半胱氨酸残基以1－5,2－4,3－6的交联方式形成三对二硫,窝囊鑫肽链折叠成特征性的三叶结构。已发现的哺乳动物三叶肽有三种：pS1、SP及ITF。三叶肽通常位于消化道腔面的粘膜层,具有保护和修复功能,在维持粘膜的完整性中发挥着重要作用。     

Mitochondrial DNA paradox: sex-specific genetic structure in a marine mussel - despite maternal inheritance and passive dispersal

ABSTRACT: BACKGROUND: When genetic structure is identified using mitochondrial DNA (mtDNA), but no structure is identified using biparentally-inherited nuclear DNA, the discordance is often attributed to differences in dispersal potential between the sexes. RESULTS: We sampled the intertidal rocky shore mussel Perna perna in a South African bay and along the nearby open coast, and sequenced maternally-inherited mtDNA (there is no evidence for paternally-inherited mtDNA in this species) and a biparentally-inherited marker. By treating males and females as different populations, we identified significant genetic structure on the basis of mtDNA data in the females only. CONCLUSIONS: This is the first study to report sex-specific differences in genetic structure based on matrilineally-inherited mtDNA in a passively dispersing species that lacks social structure or sexual dimorphism. The observed pattern most likely stems from females being more vulnerable to selection in habitats from which they did not originate, which also manifests itself in a male-biased sex ratio. Our results have three important implications for the interpretation of population genetic data. First, even when mtDNA is inherited exclusively in the female line, it also contains information about males. For that reason, using it to identify sex-specific differences in genetic structure by contrasting it with biparentally-inherited markers is problematic. Second, the fact that sex-specific differences were found in a passively dispersing species in which sex-biased dispersal is unlikely highlights the fact that significant genetic structure is not necessarily a function of low dispersal potential or physical barriers. Third, even though mtDNA is typically used to study historical demographic processes, it also contains information about contemporary processes. Higher survival rates of males in non-native habitats can erase the genetic structure present in their mothers within a single generation.     

Aromatic interactions in peptides: impact on structure and function

Aromatic interactions, including pi-pi, cation-pi, aryl-sulfur, and carbohydrate-pi interactions, have been shown to be prevalent in proteins through protein structure analysis, suggesting that they are important contributors to protein structure. However, the magnitude and significance of aromatic interactions is not defined by such studies. Investigation of aromatic interactions in the context of structured peptides has complemented studies of protein structure and has provided a wealth of information regarding the role of aromatic interactions in protein structure and function. Recent advances in this area are reviewed.     

Pore-forming peptides of Entamoeba dispar. Similarity and divergence to amoebapores in structure, expression and activity.

Amoebapore, a 77-residue peptide with pore-forming activity from the human pathogen Entamoeba histolytica, is implicated in the killing of phagocytosed bacteria and in the cytolytic reaction of the amoeba against host cells. Previously, we structurally and functionally characterized three amoebapore isoforms in E. histolytica but recognized only one homolog in the closely related but non-pathogenic species Entamoeba dispar. Here, we identified two novel amoebapore homologs from E. dispar by molecular cloning. Despite strong resemblance of the primary structures of the homologs, molecular modeling predicts a species-specific variance between the peptide structures. Parallel isolation from trophozoite extracts of the two species revealed a lower amount of pore-forming peptides in E. dispar and substantially higher activity of the major isoform from E. histolytica towards natural membranes than that from E. dispar. Differences in abundance and activity of the lytic polypeptides may have an impact on the pathogenicity of amoebae.     

Local function conservation in sequence and structure space

We assess the variability of protein function in protein sequence and structure space. Various regions in this space exhibit considerable difference in the local conservation of molecular function. We analyze and capture local function conservation by means of logistic curves. Based on this analysis, we propose a method for predicting molecular function of a query protein with known structure but unknown function. The prediction method is rigorously assessed and compared with a previously published function predictor. Furthermore, we apply the method to 500 functionally unannotated PDB structures and discuss selected examples. The proposed approach provides a simple yet consistent statistical model for the complex relations between protein sequence, structure, and function. The GOdot method is available online (http://godot.bioinf.mpi-inf.mpg.de).     

The cDNA sequence of a human epidermal keratin: divergence of sequence but conservation of structure among intermediate filament proteins

We have determined the DNA sequence of a cloned cDNA that is complementary to the mRNA for the 50 kilodalton (kd) human epidermal keratin. This provides the first amino acid sequence for a cytoskeletal keratin. Comparison of this sequence with those of other keratins reveals an evolutionary relationship between the cytoskeletal and the microfibrillar keratins, but shows no homology to matrix or feather keratins. The 50 kd keratin shares 28%-30% homology with partial sequences of other intermediate filament proteins, which suggests that keratins may be the most distantly related members of this class of fibrous proteins. Our computer analyses predict that the 50 kd keratin contains two long alpha-helical domains separated by a cluster of helix-inhibitory residues in the middle of the protein. These findings indicate that despite major sequence divergence among intermediate filament proteins, they retain sequences compatible with secondary structural features that appear to be common to all of them.     

Evolutionary conservation of RecA genes in relation to protein structure and function.

Functional and structural regions inferred from the Escherichia coli R ecA protein crystal structure and mutation studies are evaluated in terms of evolutionary conservation across 63 RecA eubacterial sequences. Two paramount segments invariant in specific amino acids correspond to the ATP-binding A site and the functionally unassigned segment from residues 145 to 149 immediately carboxyl to the ATP hydrolysis B site. Not only are residues 145 to 149 conserved individually, but also all three-dimensional structural neighbors of these residues are invariant, strongly attesting to the functional or structural importance of this segment. The conservation of charged residues at the monomer-monomer interface, emphasizing basic residues on one surface and acidic residues on the other, suggests that RecA monomer polymerization is substantially mediated by electrostatic interactions. Different patterns of conservation also allow determination of regions proposed to interact with DNA, of LexA binding sites, and of filament-filament contact regions. Amino acid conservation is also compared with activities and properties of certain RecA protein mutants. Arginine 243 and its strongly cationic structural environment are proposed as the major site of competition for DNA and LexA binding to RecA. The conserved acidic and glycine residues of the disordered loop L1 and its proximity to the RecA acidic monomer interface suggest its involvement in monomer-monomer interactions rather than DNA binding. The conservation of various RecA positions and regions suggests a model for RecA-double-stranded DNA interaction and other functional and structural assignments.     

Appearance of photochemical function in prothylakoids during plastid development.

1. A method to separate the vesicles of prothylakoids from prolamellar body preparations obtained from etiolated and rapidly greening Avena laminae (0.25--4 h illumination ) is described. The prothylakoid preparations were found to be free from contaminating prolamellar bodies but enriched prolamellar body preparations (enriched prolamellar body preparations) still contained some adhering prothylakoid material. 2. Only existing beta-carotene appears to be transferred from the prolamellar bodies to the prothylakoids during early development and this ceases when freshly synthesized beta-carotene becomes available. 3. Prolamellar body structures proper show no positive association of existing or developing photochemical activities; these are only to be found in the developing prothylakoids. 4. Using methylviologen-linked electron transport-dependent oxygen consumption, Photosystem I activities may be detected with added diaminodurene within 15 min of illumination and within 30 min and 1 h with added tetramethylphenylenediamine and dichlorophenolindophenol, respectively. 5. During the 2nd, and 3rd. h of greening, proton-pumping capability and later ATP formation increased in prothylakoids in the presence of diaminodurene. 6. The first indications of Photosystem II activity using diphenylcarbazide as electron donor are shown at a similar time (2 h) with prothylakoids. The last photochemical activity to appear is the capacity to split water (3 h) and consequently the diphenylcarbazide activity diminished to zero before 8 h of illumination have passed. 7. The lack of effect of uncouplers such as NH4+ prior to 2 h suggests that in spite of some proton-pumping ability there is the possibility of proton-leaky areas existing within prothylakoids. This lack of a persistent proton gradient before 2 h of illumination may explain the different starting times of phenazine methosulfate- and diaminodurene-dependent photophosphorylation (0.25 and 2 h, respectively).     

Mammalian hexokinase 1: Evolutionary conservation and structure to function analysis

We have amplified and sequenced the complete coding region of bovine hexokinase isoenzyme 1 (HK1) from brain RNA with PCR primers selected for sequence conservation. The sequence information was analyzed to evaluate the evolutionary and structure-function relationships among the mammalian and yeast HK isoenzymes. Structure to function analysis identified an unduplicated, invariant N-terminal domain involved in HK1 outer mitochondrial membrane targeting, as well as putative carbohydrate and nucleotide-binding sites in the regulatory and catalytic halves of HK1 essential to enzyme function. The ATP-binding site in the catalytic half of the HK1 protein resembles nucleotide-binding regions from protein kinases, with the single amino acid replacement (lysine to glutamate) in the ATP-binding site of the amino half explaining the loss of HK1 catalytic function in the regulatory domain. Sequence comparisons suggest that the 50-kDa mammalian and yeast glucokinases arose separately in evolution. In addition to providing valuable phylogenetic and structure-function insights, this work provides an efficient strategy for rapid cloning and sequencing of the coding regions for other HKs and related proteins.     

The relation between the divergence of sequence and structure in proteins.

Homologous proteins have regions which retain the same general fold and regions where the folds differ. For pairs of distantly related proteins (residue identity approximately 20%), the regions with the same fold may comprise less than half of each molecule. The regions with the same general fold differ in structure by amounts that increase as the amino acid sequences diverge. The root mean square deviation in the positions of the main chain atoms, delta, is related to the fraction of mutated residues, H, by the expression: delta(A) = 0.40 e1.87H.     

The linked conservation of structure and function in a family of high diversity: the monomeric cupredoxins

The monomeric cupredoxins are a highly divergent family of copper binding electron transport proteins that function in photosynthesis and respiration. To determine how function and structure are conserved in the context of large sequence differences, we have carried out a detailed analysis of the cupredoxins of known structure and their sequence homologs. The common structure of the cupredoxins is formed by a sandwich of two beta sheets which support a copper binding site. The structure of the deeply buried core is intimately coupled to the binding site on the surface of the protein; in each protein the conserved regions form one continuous substructure that extends from the surface active site and through the center of the molecule. Residues around the active site are conserved for functional reasons, while those deeper in the structure will be conserved for structural reasons. Together the two sets support each other.     

From cyanobacteria to plants: conservation of PII functions during plastid evolution

This article reviews the current state-of-the-art concerning the functions of the signal processing protein PII in cyanobacteria and plants, with a special focus on evolutionary aspects. We start out with a general introduction to PII proteins, their distribution, and their evolution. We also discuss PII-like proteins and domains, in particular, the similarity between ATP-phosphoribosyltransferase (ATP-PRT) and its PII-like domain and the complex between N-acetyl-l-glutamate kinase (NAGK) and its PII activator protein from oxygenic phototrophs. The structural basis of the function of PII as an ATP/ADP/2-oxoglutarate signal processor is described for Synechococcus elongatus PII. In both cyanobacteria and plants, a major target of PII regulation is NAGK, which catalyzes the committed step of arginine biosynthesis. The common principles of NAGK regulation by PII are outlined. Based on the observation that PII proteins from cyanobacteria and plants can functionally replace each other, the hypothesis that PII-dependent NAGK control was under selective pressure during the evolution of plastids of Chloroplastida and Rhodophyta is tested by bioinformatics approaches. It is noteworthy that two lineages of heterokont algae, diatoms and brown algae, also possess NAGK, albeit lacking PII; their NAGK however appears to have descended from an alphaproteobacterium and not from a cyanobacterium as in plants. We end this article by coming to the conclusion that during the evolution of plastids, PII lost its function in coordinating gene expression through the PipX-NtcA network but preserved its role in nitrogen (arginine) storage metabolism, and subsequently took over the fine-tuned regulation of carbon (fatty acid) storage metabolism, which is important in certain developmental stages of plants.     

Trophic divergence despite morphological convergence in a continental radiation of snakes

Ecological and phenotypic convergence is a potential outcome of adaptive radiation in response to ecological opportunity. However, a number of factors may limit convergence during evolutionary radiations, including interregional differences in biogeographic history and clade-specific constraints on form and function. Here, we demonstrate that a single clade of terrestrial snakes from Australia—the oxyuranine elapids—exhibits widespread morphological convergence with a phylogenetically diverse and distantly related assemblage of snakes from North America. Australian elapids have evolved nearly the full spectrum of phenotypic modalities that occurs among North American snakes. Much of the convergence appears to involve the recurrent evolution of stereotyped morphologies associated with foraging mode, locomotion and habitat use. By contrast, analysis of snake diets indicates striking divergence in feeding ecology between these faunas, partially reflecting regional differences in ecological allometry between Australia and North America. Widespread phenotypic convergence with the North American snake fauna coupled with divergence in feeding ecology are clear examples of how independent continental radiations may converge along some ecological axes yet differ profoundly along others.     

The phosphorylation state of chloroplast transit peptides regulates preprotein import

Import of nuclear encoded proteins into chloroplast is an essential and well-regulated mechanism. The cytosolic kinases STY8, STY17 and STY46 have been shown to phosphorylate chloroplast preprotein transit peptides advantaging the binding of a 14-3-3 dimer. Analyses of sty8 sty17 sty46 mutant plants revealed a role for the kinases in chloroplast differentiation, possibly due to lack of transit peptide phosphorylation. Moreover we could show that not only phosphorylation but also transit peptide dephosphorylation appears to be required for the fine regulation of the back-transport of nuclear encoded proteins to the chloroplast.