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PubMed1996

Oxidation states of the manganese cluster during the flash-induced S-state cycle of the photosynthetic oxygen-evolving complex.

The Mn K-edge x-ray absorption spectra for the pure S states of the tetranuclear Mn cluster of the oxygen-evolving complex of photosystem II during flash-induced S-state cycling have been determined. The relative S-state populations in samples given 0, 1, 2, 3, 4, or 5 flashes were determined from fitting the flash-induced electron paramagnetic resonance (EPR) multiline signal oscillation pattern to the Kok model. The edge spectra of samples given 0, 1, 2, or 3 flashes were combined with EPR information to calculate the pure S-state edge spectra. The edge positions (defined as the zero-crossing of the second derivatives) are 6550.1, 6551.7, 6553.5, and 6553.8 eV for S0, S1, S2, and S3, respectively. In addition to the shift in edge position, the S0--> S1 and S1--> S2 transitions are accompanied by characteristic changes in the shape of the edge, both indicative of Mn oxidation. The edge position shifts very little (0.3 eV) for the S2--> S3 transition, and the edge shape shows only subtle changes. We conclude that probably no direct Mn oxidation is involved in this transition. The proposed Mn oxidation state assignments are as follows: S0 (II, III, IV, IV) or (III, III, III, IV), S1 (III, III, IV, IV), S2 (III, IV, IV, IV), S3 (III, IV, IV, IV).

Journal Article↗
PubMed1999

Dimerization of zinc fingers mediated by peptides evolved in vitro from random sequences.

Peptides that mediate dimerization of attached zinc finger DNA-binding domains have been evolved in vitro starting from random sequences. We first used phage display to select dimerization elements from libraries of random 15-residue polypeptides that were fused to the N terminus of the zinc finger domains. We then reoptimized these peptides by sequentially randomizing five-residue blocks (proceeding across the peptide in three steps) and selecting variant peptides that further stabilized the protein-DNA complex. Biochemical experiments confirmed that the selected peptides promote dimerization of the zinc fingers on an appropriate DNA target site. These results demonstrate that dimerization units can be obtained readily from random polypeptide libraries of moderate complexity. Our success reemphasizes the utility of searching random peptide libraries in protein design projects, and the sequences presented here may be useful when designing novel transcription factors.

Amino Acid Sequence↗
PubMed1999

Duplicated genes evolve independently after polyploid formation in cotton.

Of the many processes that generate gene duplications, polyploidy is unique in that entire genomes are duplicated. This process has been important in the evolution of many eukaryotic groups, and it occurs with high frequency in plants. Recent evidence suggests that polyploidization may be accompanied by rapid genomic changes, but the evolutionary fate of discrete loci recently doubled by polyploidy (homoeologues) has not been studied. Here we use locus-specific isolation techniques with comparative mapping to characterize the evolution of homoeologous loci in allopolyploid cotton (Gossypium hirsutum) and in species representing its diploid progenitors. We isolated and sequenced 16 loci from both genomes of the allopolyploid, from both progenitor diploid genomes and appropriate outgroups. Phylogenetic analysis of the resulting 73.5 kb of sequence data demonstrated that for all 16 loci (14.7 kb/genome), the topology expected from organismal history was recovered. In contrast to observations involving repetitive DNAs in cotton, there was no evidence of interaction among duplicated genes in the allopolyploid. Polyploidy was not accompanied by an obvious increase in mutations indicative of pseudogene formation. Additionally, differences in rates of divergence among homoeologues in polyploids and orthologues in diploids were indistinguishable across loci, with significant rate deviation restricted to two putative pseudogenes. Our results indicate that most duplicated genes in allopolyploid cotton evolve independently of each other and at the same rate as those of their diploid progenitors. These indications of genic stasis accompanying polyploidization provide a sharp contrast to recent examples of rapid genomic evolution in allopolyploids.

Biological Evolution↗
PubMed1999

A complex ligase ribozyme evolved in vitro from a group I ribozyme domain.

Like most proteins, complex RNA molecules often are modular objects made up of distinct structural and functional domains. The component domains of a protein can associate in alternative combinations to form molecules with different functions. These observations raise the possibility that complex RNAs also can be assembled from preexisting structural and functional domains. To test this hypothesis, an in vitro evolution procedure was used to isolate a previously undescribed class of complex ligase ribozymes, starting from a pool of 10(16) different RNA molecules that contained a constant region derived from a large structural domain that occurs within self-splicing group I ribozymes. Attached to this constant region were three hypervariable regions, totaling 85 nucleotides, that gave rise to the catalytic motif within the evolved catalysts. The ligase ribozymes catalyze formation of a 3',5'-phosphodiester linkage between adjacent template-bound oligonucleotides, one bearing a 3' hydroxyl and the other a 5' triphosphate. Ligation occurs in the context of a Watson-Crick duplex, with a catalytic rate of 0.26 min(-1) under optimal conditions. The constant region is essential for catalytic activity and appears to retain the tertiary structure of the group I ribozyme. This work demonstrates that complex RNA molecules, like their protein counterparts, can share common structural domains while exhibiting distinct catalytic functions.

Animals↗
PubMed1999

Homospermidine synthase, the first pathway-specific enzyme of pyrrolizidine alkaloid biosynthesis, evolved from deoxyhypusine synthase.

Pyrrolizidine alkaloids are preformed plant defense compounds with sporadic phylogenetic distribution. They are thought to have evolved in response to the selective pressure of herbivory. The first pathway-specific intermediate of these alkaloids is the rare polyamine homospermidine, which is synthesized by homospermidine synthase (HSS). The HSS gene from Senecio vernalis was cloned and shown to be derived from the deoxyhypusine synthase (DHS) gene, which is highly conserved among all eukaryotes and archaebacteria. DHS catalyzes the first step in the activation of translation initiation factor 5A (eIF5A), which is essential for eukaryotic cell proliferation and which acts as a cofactor of the HIV-1 Rev regulatory protein. Sequence comparison provides direct evidence for the evolutionary recruitment of an essential gene of primary metabolism (DHS) for the origin of the committing step (HSS) in the biosynthesis of pyrrolizidine alkaloids.

Alkyl and Aryl Transferases↗
PubMed1999

Transmission bottlenecks as determinants of virulence in rapidly evolving pathogens.

Transmission bottlenecks occur in pathogen populations when only a few individual pathogens are transmitted from one infected host to another in the initiation of a new infection. Transmission bottlenecks can dramatically affect the evolution of virulence in rapidly evolving pathogens such as RNA viruses. Characterizing pathogen diversity with the quasispecies concept, we use analytical and simulation methods to demonstrate that severe bottlenecks are likely to drive down the virulence of a pathogen because of stochastic loss of the most virulent pathotypes, through a process analogous to Muller's ratchet. We investigate in this process the roles of host population size, duration of within-host viral replication, and transmission bottleneck size. We argue that the patterns of accumulation of deleterious mutation may explain differing levels of virulence in vertically and horizontally transmitted diseases.

Evolution, Molecular↗
PubMed1999

Phylogeny of a rapidly evolving clade: the cichlid fishes of Lake Malawi, East Africa.

Lake Malawi contains a flock of >500 species of cichlid fish that have evolved from a common ancestor within the last million years. The rapid diversification of this group has been attributed to morphological adaptation and to sexual selection, but the relative timing and importance of these mechanisms is not known. A phylogeny of the group would help identify the role each mechanism has played in the evolution of the flock. Previous attempts to reconstruct the relationships among these taxa using molecular methods have been frustrated by the persistence of ancestral polymorphisms within species. Here we describe results from a DNA fingerprinting technique that overcomes this problem by examining thousands of polymorphisms distributed across the genome. The resulting dendrogram averages the evolutionary history of thousands of genes and should accurately reflect the evolutionary history of these species. Our tree resolves relationships among closely related Lake Malawi cichlids and provides insights into the pattern of speciation in this group. We demonstrate that adaptive divergence in trophic morphology played an important role during the early history of the lake. Subsequent species diversity has arisen with little change in trophic morphology, which suggests that other forces are responsible for the continued speciation of these fishes.

Africa, Eastern↗
PubMed2001

Fitness effects of advantageous mutations in evolving Escherichia coli populations.

The central role of beneficial mutations for adaptive processes in natural populations is well established. Thus, there has been a long-standing interest to study the nature of beneficial mutations. Their low frequency, however, has made this class of mutations almost inaccessible for systematic studies. In the absence of experimental data, the distribution of the fitness effects of beneficial mutations was assumed to resemble that of deleterious mutations. For an experimental proof of this assumption, we used a novel marker system to trace adaptive events in an evolving Escherichia coli culture and to determine the selective advantage of those beneficial mutations. Ten parallel cultures were propagated for about 1,000 generations by serial transfer, and 66 adaptive events were identified. From this data set, we estimate the rate of beneficial mutations to be 4 x 10(-9) per cell and generation. Consistent with an exponential distribution of the fitness effects, we observed a large fraction of advantageous mutations with a small effect and only few with large effect. The mean selection coefficient of advantageous mutations in our experiment was 0.02.

Acclimatization↗
PubMed2001

Does clutch size evolve in response to parasites and immunocompetence?

Parasites have been argued to influence clutch size evolution, but past work and theory has largely focused on within-species optimization solutions rather than clearly addressing among-species variation. The effects of parasites on clutch size variation among species can be complex, however, because different parasites can induce age-specific differences in mortality that can cause clutch size to evolve in different directions. We provide a conceptual argument that differences in immunocompetence among species should integrate differences in overall levels of parasite-induced mortality to which a species is exposed. We test this assumption and show that mortality caused by parasites is positively correlated with immunocompetence measured by cell-mediated measures. Under life history theory, clutch size should increase with increased adult mortality and decrease with increased juvenile mortality. Using immunocompetence as a general assay of parasite-induced mortality, we tested these predictions by using data for 25 species. We found that clutch size increased strongly with adult immunocompetence. In contrast, clutch size decreased weakly with increased juvenile immunocompetence. But, immunocompetence of juveniles may be constrained by selection on adults, and, when we controlled for adult immunocompetence, clutch size decreased with juvenile immunocompetence. Thus, immunocompetence seems to reflect evolutionary differences in parasite virulence experienced by species, and differences in age-specific parasite virulence appears to exert opposite selection on clutch size evolution.

Animals↗
PubMed1995

The human COL11A2 gene structure indicates that the gene has not evolved with the genes for the major fibrillar collagens.

The human COL11A2 gene was analyzed from two overlapping cosmid clones that were previously isolated in the course of searching the human major histocompatibility region (Janatipour, M., Naumov, Y., Ando, A., Sugimura, K., Okamoto, N., Tsuji, K., Abe, K., and Inoko, H. (1992) Immunogenetics 35, 272-278). Nucleotide sequencing defined over 28,000 base pairs of the gene. It was shown to contain 66 exons. As with most genes for fibrillar collagens, the first intron was among the largest, and the introns at the 5'-end of the gene were in general larger than the introns at the 3'-end. Analysis of the exons coding for the major triple helical domain indicated that the gene structure had not evolved with the genes for the major fibrillar collagens in that there were marked differences in the number of exons, the exon sizes, and codon usage. The gene was located close to the gene for the retinoic X receptor beta in a head-to-tail arrangement similar to that previously seen with the two mouse genes (P. Vandenberg and D. J. Prockop, submitted for publication). Also, there was marked interspecies homology in the intergenic sequences. The amino acid sequences and the pattern of charged amino acids in the major triple helix of the alpha 2(XI) chain suggested that the chain can be incorporated into the same molecule as alpha 1(XI) and alpha 1(V) chains but not into the same molecule as the alpha 3(XI)/alpha 1(II) chain. The structure of the carboxyl-terminal propeptide was similar to the carboxyl-terminal propeptides of the pro alpha 1(XI) chain and pro alpha chains of other fibrillar collagens, but it was shorter because of internal deletions of about 30 amino acids.

Amino Acid Sequence↗
PubMed1995

Role of the RCII-D1 protein in the reversible association of the oxygen-evolving complex proteins with the lumenal side of photosystem II.

The nuclear-encoded proteins of the oxygen-evolving complex (OEC) of photosystem II are bound on the lumenal side of the thylakoid membrane and stabilize the manganese ion cluster forming the photosystem II electron donor side. The OEC proteins are released from their binding site(s) following light-induced degradation of reaction center II (RCII)-D1 protein in Chlamydomonas reinhardtii. The kinetics of OEC proteins release correlates with that of RCII-D1 protein degradation. Only a limited amount of RCII-D2 protein is degraded during the process, and no loss of the core proteins CP43 and CP47 is detected. The release of the OEC proteins is prevented when the photoinactivated RCII-D1 protein degradation is retarded by addition of 3-(3,5-dichlorophenyl)-1,1-dimethylurea or by a high PQH2/PQ ratio prevailing in membranes of the plastocyanin-deficient mutant Ac208. The released proteins are not degraded but persist in the thylakoid lumen for up to 8 h and reassociate with photosystem II when new D1 protein is synthesized in cells exposed to low light, thus allowing recovery of photosystem II function. Reassociation also occurs following D1 protein synthesis in darkness when RCII activity is only partially recovered. These results indicate that (i) the D1 protein participates in the formation of the lumenal OEC proteins binding site(s) and (ii) the photoinactivation of RCII-D1 protein does not alter the conformation of the donor side of photosystem II required for the binding of the OEC proteins.

Animals↗
PubMed2001

The location of the ligand-binding site of carbohydrate-binding modules that have evolved from a common sequence is not conserved.

Polysaccharide-degrading enzymes are generally modular proteins that contain non-catalytic carbohydrate-binding modules (CBMs), which potentiate the activity of the catalytic module. CBMs have been grouped into sequence-based families, and three-dimensional structural data are available for half of these families. Clostridium thermocellum xylanase 11A is a modular enzyme that contains a CBM from family 6 (CBM6), for which no structural data are available. We have determined the crystal structure of this module to a resolution of 2.1 A. The protein is a beta-sandwich that contains two potential ligand-binding clefts designated cleft A and B. The CBM interacts primarily with xylan, and NMR spectroscopy coupled with site-directed mutagenesis identified cleft A, containing Trp-92, Tyr-34, and Asn-120, as the ligand-binding site. The overall fold of CBM6 is similar to proteins in CBM families 4 and 22, although surprisingly the ligand-binding site in CBM4 and CBM22 is equivalent to cleft B in CBM6. These structural data define a superfamily of CBMs, comprising CBM4, CBM6, and CBM22, and demonstrate that, although CBMs have evolved from a relatively small number of ancestors, the structural elements involved in ligand recognition have been assembled at different locations on the ancestral scaffold.

Amino Acid Sequence↗
PubMed2002

Three-dimensional electron cryo-microscopy study of the extrinsic domains of the oxygen-evolving complex of spinach: assignment of the PsbO protein.

Three independent three-dimensional reconstructions of the spinach photosystem II-light-harvesting complex supercomplex were derived from single particle analyses of non-stained, vitrified samples imaged by electron microscopy. Each reconstruction was found to differ significantly in the composition of the lumenal oxygen-evolving complex extrinsic proteins. From difference mapping, aided by electron microscopy of negatively stained selectively washed samples, regions of density were assigned to the PsbO and PsbP/PsbQ proteins. Interpretation of the density assigned to the PsbO protein was explored using computer-aided structural predictions. PsbO is calculated to be mainly a beta-protein (38% beta) composed of two domains within an overall elongated shape (Pazos, F., Heredia, P., Valencia, A., and De Las Rivas, J. (2001) Proteins Struct. Funct. Genet. 45, 372-381). The positioning and fitting of the proposed structural model for the PsbO protein within the three-dimensional map indicated that there is a single copy per reaction center. Moreover, the structural model derived for PsbO, together with difference mapping, indicates that this protein stretches across the surface of the reaction center with its N- and C-terminal domains located toward the CP47 and CP43 side, respectively. This structural assignment is discussed in terms of the recent x-ray-derived cyanobacterial model of PSII (Zouni, A., Witt, H.-T., Kern, J., Fromme, P., Krauss, N., Saenger, W., and Orth, P. (2001) Nature 409, 739-743).

Cryoelectron Microscopy↗
PubMed2006

Regulation of G protein-coupled receptor trafficking by inefficient plasma membrane expression: molecular basis of an evolved strategy.

Despite the prevalence of G protein-coupled receptors as transducers of signals from hormones, neurotransmitters, odorants, and light, little is known about mechanisms that regulate their plasma membrane expression (PME), although misfolded receptors are recognized and retained by a cellular quality control system (QCS). Convergent evolution of the gonadotropin-releasing hormone (GnRH) receptor (GnRHR) progressively decreases inositol phosphate production in response to agonist, validated as a measure of PME of receptor. A pharmacological chaperone that optimizes folding also increases PME of human, but not of rat or mouse, GnRHR because a higher percentage of human GnRHRs are misfolded structures due to their failure to form an apparent sulfhydryl bridge, and they are retained by the QCS. Bridge formation is increased by deleting (primate-specific) Lys191. In rat or mouse GnRHR that lacks Lys191, the bridge is non-essential and receptor is efficiently routed to the plasma membrane. Addition of Lys191 alone to the rat sequence did not diminish PME, indicating that other changes are required for its effects. A strategy, based on identification of amino acids that both 1) co-evolved with the Lys191 and 2) were thermodynamically unfavorable substitutions, identified motifs in multiple domains of the human receptor that control the destabilizing influence of Lys191 on a particular Cys bridge, resulting in diminished PME. The data show a novel and underappreciated means of posttranslational control of a G protein-coupled receptor by altering its interaction with the QCS and provide a biochemical explanation of the basis of disease-causing mutations of this receptor.

Amino Acid Motifs↗
PubMed2004

The oxygen evolving enhancer protein 1 (OEE) of photosystem II in green algae exhibits thioredoxin activity.

A thioredoxin-like chloroplast protein of the fructosebisphosphatase-stimulating f-type, but with an unusually high molecular mass of 28 kDa has previously been identified and purified to homogeneity in a fractionation scheme for resolution of the acid- and heat-stable, regular-size (12kDa) thioredoxins of the unicellular green algae, Scenedesmus obliquus. An apparently analogous protein of 26 kDa was described in a cyanobacterium, Anabaena sp., but no such large thioredoxin species f exists in the thioredoxin profiles of higher plants. The structure of the 28 kDa protein, which had been envisaged to represent a precursor, or fusion product of the two more specialized, common chloroplast thioredoxins f and m has now been determined by amino acid sequencing. Although it exhibits virtually all the properties and enzyme-modulating activities of a thioredoxin proper this algal protein, surprisingly, does not belong to the thioredoxin family of small redox proteins but is identical with OEE (oxygen evolving enhancer) protein 1, an auxiliary component of the photosystem II manganese cluster. Extracts of Chlorella vulgaris and Chlamydomonas reinhardtii also contain heat-stable protein fractions of 23-26 kDa capable of specifically stimulating chloroplast fructosebisphosphatase in vitro. In contrast, OEE protein 1 from spinach is not able to modulate FbPase or NADP malate dehydrogenase from spinach chloroplasts. A dual function of the OEE protein in algal photosynthesis is envisaged.

Algal Proteins↗
PubMed2006

Evolvable work-centred support systems for command and control: creating systems users can adapt to meet changing demands.

Military command and control (C2) organizations are complex socio-technical systems which must constantly adapt to meet changing operational requirements. We describe our experiences in developing a work-centred support system (WCSS) to aid weather forecasting and monitoring in a military airlift C2 organization as an illustrative case. As part of the development process we conducted field observations both before and after introduction of the WCSS in their operations centre. A striking finding was the constant changes that operations personnel faced (changes in goals and priorities, changes in scale of operations, changes in team roles and structure, and changes in information sources and systems). We describe the changes in workplace demands that we observed and the modifications we needed to make to the WCSS in response. For today's fielded systems, it is seldom possible to make changes that are responsive to users' changing requirements in a timely manner. We argue for the need to incorporate facilities that enable users to adapt their systems to the changing requirements of work and point to some promising directions towards evolvable work-centred support systems.

Data Collection↗
PubMedDate not supplied

The evolving concept of renal neoplasia: impact of emerging molecular and electron microscopic studies.

The classification of renal tumors has evolved from one that initially encompassed only 2 types of tumors, i.e., clear and granular cell carcinomas, to the markedly expanded recent classification that incorporates new entities, some of which are primarily defined by specific molecular abnormalities. Despite these advances, a single tumor category, clear cell carcinoma, still incorporates the majority (approximately 70%) of renal tumors. It is, however, postulated that this single category is likely to encompass several different tumor types that are, at present, undifferentiated. Electron microscopic studies have been pivotal in defining the spectrum of oncocytoma-chromophobe renal cell carcinoma. Cytoplasmic eosinophilia found in some renal cell carcinomas currently classified as clear cell type is under intense study. Tumors that have recently emerged from this group include tumors with translocations involving chromosome Xp11.2, carcinomas associated with neuroblastoma and epithelioid angiomyolipoma. The spectrum of renal tumors seen in younger patients is wider than among older patients, with rare and unusual tumors being more likely seen in younger patients. The author concludes that although the routine application of electron microscopy to kidney tumor diagnosis may not be practical, systematic ultrastructural studies of these tumors may aid in the definition of new entities.

Chromosome Aberrations↗
PubMed2000

Evolving experience in the management of empyema thoracis.

The optimal management of paediatric empyema thoracis remains controversial. The objective of the study was to analyse evolving experience in clinical presentation, management, outcome and factors contributing to adverse morbidity in thoracic empyema. Forty-seven patients presenting to a paediatric surgical centre were studied in three consecutive 6-y periods during 1980-97 to compare any change in the pattern of disease influencing diagnosis and management. Patients were categorized into two treatment groups: (i) conservative management (antibiotics and/or tube thoracostomy), (ii) thoracotomy. The median duration of illness prior to hospital admission was 10 d (range 1-42 d). Ultrasound was increasingly utilized in the diagnosis and staging of empyema and played an important role in directing definitive management. The presence of loculated pleural fluid determined the need for thoracotomy. Sixteen of 20 patients (80%) who were initially treated with thoracocentesis or tube thoracostomy eventually needed thoracotomy. There was a positive shift in management towards early thoracotomy resulting in prompt symptomatic recovery. Significant complications were noted in seven children who had delayed thoracotomy. These included recurrent empyema with lung abscess (n = 2), scoliosis (n = 2), restrictive lung disease (n = 1), bronchopleural fistula (n = 1) and sympathetic pericardial effusion (n = 1). An unfavourable experience with delayed thoracotomy during the study period has led us to adopt a more aggressive early operative approach to empyema thoracis. The decision to undertake thoracotomy has been influenced by the ultrasound findings of organized loculated pleural fluid. Delayed surgery was associated with adverse outcome. Whilst fibrinolytics and thoracoscopy may provide attractive options for early empyema, thoracotomy can hasten patient recovery regardless of the stage of disease. Prospective randomized trials are required to assess the ideal therapy for childhood empyema.

Adolescent↗