Orthologs and paralogs - we need to get it right

A response to Homologuephobia, by Gregory A Petsko, Genome Biology 2001 2:comment1002.1-1002.2, to An apology for orthologs - or brave new memes by Eugene V Koonin, Genome Biology 2001, 2:comment1005.1-1005.2, and to Can sequence determine function? by John A Gerlt and Patricia C Babbitt, Genome Biology 2000, 1:reviews0005.1-0005.10

A Bell-Evans-Polanyi principle for molecular dynamics trajectories and its implications for global optimization

The Bell-Evans-Polanyi principle that is valid for a chemical reaction that proceeds along the reaction coordinate over the transition state is extended to molecular dynamics trajectories that in general do not cross the dividing surface between the initial and the final local minima at the exact transition state. Our molecular dynamics Bell-Evans-Polanyi principle states that low energy molecular dynamics trajectories are more likely to lead into the basin of attraction of a low energy local minimum than high energy trajectories. In the context of global optimization schemes based on molecular dynamics our molecular dynamics Bell-Evans-Polanyi principle implies that using low energy trajectories one needs to visit a smaller number of distinguishable local minima before finding the global minimum than when using high energy trajectories

Addressing factory needs in cane variety selection

Cane fibre content has increased over the past ten years. Some of that increase can be attributed to new varieties selected for release. This paper reviews the existing methods for quantifying the fibre characteristics of a variety, including fibre content and fibre quality measurements – shear strength, impact resistance and short fibre content. The variety selection process is presented and it is reported that fibre content has zero weighting in the current selection index. An updated variety selection approach is proposed, potentially replacing the existing selection process relating to fibre. This alternative approach involves the use of a more complex mill area level model that accounts for harvesting, transport and processing equipment, taking into account capacity, efficiency and operational impacts, along with the end use for the bagasse. The approach will ultimately determine a net economic value for the variety. The methodology lends itself to a determination of the fibre properties that have a significant impact on the economic value so that variety tests can better target the critical properties. A low-pressure compression test is proposed as a good test to provide an assessment of the impact of a variety on milling capacity. NIR methodology is proposed as a technology to lead to a more rapid assessment of fibre properties, and hence the opportunity to more comprehensively test for fibre impacts at an earlier stage of variety development

Case Studies of Dewatering and Foundation Design: Retail Warehouses in Taiwan

The case studies in this paper describe three retail warehouse sites in Taiwan that have high groundwater tables in common, but that have drastically different soil conditions. Two of the sites are in dense, permeable gravel and cobble and the third site is in interbedded alluvial sand and clay. At the first site, shallow footings and slab-on-grade floors were placed on top of a permanent passive drainage system that required accurate seepage volume estimates in the permeable gravel and cobble. At the second site, the hydraulic conductivity of the gravel and cobble is high and is sensitive to fluctuation of the regional groundwater table. A hybrid passive drainage and structural slab system minimizes pumping during the seasonal high groundwater table. At the third site, deep slurry walls constructed around the building cut off groundwater seepage, and permanent pumping wells within the building footprint lower the groundwater table. This system also eliminated the risk of soil liquefaction and allowed shallow footings and slab-on-grade floors to be used. This paper discusses the hydrogeological analysis of the three sites and the geotechnical design considerations for the dewatering and foundation systems, as well as soil liquefaction mitigation

Le cofinancement usager - contribuable et le partenariat public - privé changent les termes de l'évaluation des programmes d'investissement public

Bien qu'il puisse être appliqué à diverses sortes d'équipements publics, l'objet de cet article concerne les investissements d'infrastructure dans le secteur des transports. Il pose le problème de l'articulation entre les évaluations économiques et financières. Il s'agit d'optimiser le rendement social au sens du calcul économique, mais en prenant en compte deux aspects trop négligés : d'une part, le fait que la plupart des grands investissements candidats seront cofinancés par l'usager et le contribuable, comme l'ont été les investissements récents ; d'autre part, la nécessité de ne pas seulement raisonner sur la détermination du meilleur projet, mais sur la détermination du meilleur programme de projets. Cet article montre l'attrait du ratio de « l'utilité collective par euro public investi », en tant que critère permettant appréhender les effets de l'intensification de la contrainte financière publique.Infrastructure ; investissement ; ordre ; choix public

Dynamic diversity of the tryptophan pathway in chlamydiae: reductive evolution and a novel operon for tryptophan recapture

BACKGROUND: Complete genomic sequences of closely related organisms, such as the chlamydiae, afford the opportunity to assess significant strain differences against a background of many shared characteristics. The chlamydiae are ubiquitous intracellular parasites that are important pathogens of humans and other organisms. Tryptophan limitation caused by production of interferon-γ by the host and subsequent induction of indoleamine dioxygenase is a key aspect of the host-parasite interaction. It appears that the chlamydiae have learned to recognize tryptophan depletion as a signal for developmental remodeling. The consequent non-cultivable state of persistence can be increasingly equated to chronic disease conditions. RESULTS: The genes encoding enzymes of tryptophan biosynthesis were the focal point of this study. Chlamydophila psittaci was found to possess a compact operon containing PRPP synthase, kynureninase, and genes encoding all but the first step of tryptophan biosynthesis. All but one of the genes exhibited translational coupling. Other chlamydiae (Chlamydia trachomatis, C. muridarum and Chlamydophila pneumoniae) lack genes encoding PRPP synthase, kynureninase, and either lack tryptophan-pathway genes altogether or exhibit various stages of reductive loss. The origin of the genes comprising the trp operon does not seem to have been from lateral gene transfer. CONCLUSIONS: The factors that accommodate the transition of different chlamydial species to the persistent (chronic) state of pathogenesis include marked differences in strategies deployed to obtain tryptophan from host resources. C. psittaci appears to have a novel mechanism for intercepting an early intermediate of tryptophan catabolism and recycling it back to tryptophan. In effect, a host-parasite metabolic mosaic has evolved for tryptophan recycling

Significance of two distinct types of tryptophan synthase beta chain in Bacteria, Archaea and higher plants

BACKGROUND: Tryptophan synthase consists of two subunits, α and β. Two distinct subgroups of β chain exist. The major group (TrpEb_1) includes the well-studied β chain of Salmonella typhimurium. The minor group of β chain (TrpEb_2) is most frequently found in the Archaea. Most of the amino-acid residues important for catalysis are highly conserved between both TrpE subfamilies. RESULTS: Conserved amino-acid residues of TrpEb_1 that make allosteric contact with the TrpEa subunit (the α chain) are absent in TrpEb_2. Representatives of Archaea, Bacteria and higher plants all exist that possess both TrpEb_1 and TrpEb_2. In those prokaryotes where two trpEb genes coexist, one is usually trpEb_1 and is adjacent to trpEa, whereas the second is trpEb_2 and is usually unlinked with other tryptophan-pathway genes. CONCLUSIONS: TrpEb_1 is nearly always partnered with TrpEa in the tryptophan synthase reaction. However, by default at least six lineages of the Archaea are likely to use TrpEb_2 as the functional β chain, as TrpEb_1 is absent. The six lineages show a distinctive divergence within the overall TrpEa phylogenetic tree, consistent with the lack of selection for amino-acid residues in TrpEa that are otherwise conserved for interfacing with TrpEb_1. We suggest that the standalone function of TrpEb_2 might be to catalyze the serine deaminase reaction, an established catalytic capability of tryptophan synthase β chains. A coincident finding of interest is that the Archaea seem to use the citramalate pathway, rather than threonine deaminase (IlvA), to initiate the pathway of isoleucine biosynthesis

Palynostratigraphy of the Eocene Little River Section, Grays Harbor County, Washington

A total of 27 samples from Eocene marine rocks exposed along the Little River, Grays Harbor County, southwestern Washington were analyzed for palynomorphs. Strata studied included the Crescent Formation, Sedimentary Rocks of Late Eocene Age , and the Lincoln Creek Formation. A total of 77 micro fossil types were identified of which 32 were pollen and spores, 24 fungal remains, 18 dinoflagellate cysts, and 3 miscellaneous micro fossils. Based upon the stratigraphic distribution of 21 palynomorphs, three informal palynologic assemblage biozones were recognized. The oldest zone, Zone 1, of late early or early middle Eocene age, contains Platycaryapollenites, Platanoidites, Laevigatosporites type-2, trilete type-2 and D-6 dinoflagellates. Zone 2, of middle Eocene age, is recognized by the presence of Proteacidites Laevigatosporites type-2, tricolpate reticulate type-1,trilete type-2, and D-14 and D-15 dinoflagellates. Zone 3, of late Eocene age, is recognized by Tsugapollenites, Bombacacidites, Tiliaepollenites, Selaginella, Inaperturopollenites type-2, and D-8 dinoflagellates. None of the palynozones established by previous Pacific Northwest palynologic investigations were recognized in this study

The TyrA family of aromatic-pathway dehydrogenases in phylogenetic context

BACKGROUND: The TyrA protein family includes members that catalyze two dehydrogenase reactions in distinct pathways leading to L-tyrosine and a third reaction that is not part of tyrosine biosynthesis. Family members share a catalytic core region of about 30 kDa, where inhibitors operate competitively by acting as substrate mimics. This protein family typifies many that are challenging for bioinformatic analysis because of relatively modest sequence conservation and small size. RESULTS: Phylogenetic relationships of TyrA domains were evaluated in the context of combinatorial patterns of specificity for the two substrates, as well as the presence or absence of a variety of fusions. An interactive tool is provided for prediction of substrate specificity. Interactive alignments for a suite of catalytic-core TyrA domains of differing specificity are also provided to facilitate phylogenetic analysis. tyrA membership in apparent operons (or supraoperons) was examined, and patterns of conserved synteny in relationship to organismal positions on the 16S rRNA tree were ascertained for members of the domain Bacteria. A number of aromatic-pathway genes (hisH(b), aroF, aroQ) have fused with tyrA, and it must be more than coincidental that the free-standing counterparts of all of the latter fused genes exhibit a distinct trace of syntenic association. CONCLUSION: We propose that the ancestral TyrA dehydrogenase had broad specificity for both the cyclohexadienyl and pyridine nucleotide substrates. Indeed, TyrA proteins of this type persist today, but it is also common to find instances of narrowed substrate specificities, as well as of acquisition via gene fusion of additional catalytic domains or regulatory domains. In some clades a qualitative change associated with either narrowed substrate specificity or gene fusion has produced an evolutionary "jump" in the vertical genealogy of TyrA homologs. The evolutionary history of gene organizations that include tyrA can be deduced in genome assemblages of sufficiently close relatives, the most fruitful opportunities currently being in the Proteobacteria. The evolution of TyrA proteins within the broader context of how their regulation evolved and to what extent TyrA co-evolved with other genes as common members of aromatic-pathway regulons is now feasible as an emerging topic of ongoing inquiry

Inter-genomic displacement via lateral gene transfer of bacterial trp operons in an overall context of vertical genealogy

BACKGROUND: The growing conviction that lateral gene transfer plays a significant role in prokaryote genealogy opens up a need for comprehensive evaluations of gene-enzyme systems on a case-by-case basis. Genes of tryptophan biosynthesis are frequently organized as whole-pathway operons, an attribute that is expected to facilitate multi-gene transfer in a single step. We have asked whether events of lateral gene transfer are sufficient to have obscured our ability to track the vertical genealogy that underpins tryptophan biosynthesis. RESULTS: In 47 complete-genome Bacteria, the genes encoding the seven catalytic domains that participate in primary tryptophan biosynthesis were distinguished from any paralogs or xenologs engaged in other specialized functions. A reliable list of orthologs with carefully ascertained functional roles has thus been assembled and should be valuable as an annotation resource. The protein domains associated with primary tryptophan biosynthesis were then concatenated, yielding single amino-acid sequence strings that represent the entire tryptophan pathway. Lateral gene transfer of several whole-pathway trp operons was demonstrated by use of phylogenetic analysis. Lateral gene transfer of partial-pathway trp operons was also shown, with newly recruited genes functioning either in primary biosynthesis (rarely) or specialized metabolism (more frequently). CONCLUSIONS: (i) Concatenated tryptophan protein trees are congruent with 16S rRNA subtrees provided that the genomes represented are of sufficiently close phylogenetic spacing. There are currently seven tryptophan congruency groups in the Bacteria. Recognition of a succession of others can be expected in the near future, but ultimately these should coalesce to a single grouping that parallels the 16S rRNA tree (except for cases of lateral gene transfer). (ii) The vertical trace of evolution for tryptophan biosynthesis can be deduced. The daunting complexities engendered by paralogy, xenology, and idiosyncrasies of nomenclature at this point in time have necessitated an expert-assisted manual effort to achieve a correct analysis. Once recognized and sorted out, paralogy and xenology can be viewed as features that enrich evolutionary histories