Defining structural and evolutionary modules in proteins: a community detection approach to explore sub-domain architecture.

BACKGROUND: Assessing protein modularity is important to understand protein evolution. Still the question of the existence of a sub-domain modular architecture remains. We propose a graph-theory approach with significance and power testing to identify modules in protein structures. In the first step, clusters are determined by optimizing the partition that maximizes the modularity score. Second, each cluster is tested for significance. Significant clusters are referred to as modules. Evolutionary modules are identified by analyzing homologous structures. Dynamic modules are inferred from sets of snapshots of molecular simulations. We present here a methodology to identify sub-domain architecture robustly, biologically meaningful, and statistically supported. RESULTS: The robustness of this new method is tested using simulated data with known modularity. Modules are correctly identified even when there is a low correlation between landmarks within a module. We also analyzed the evolutionary modularity of a data set of α-amylase catalytic domain homologs, and the dynamic modularity of the Niemann-Pick C1 (NPC1) protein N-terminal domain.The α-amylase contains an (α/ß)8 barrel (TIM barrel) with the polysaccharides cleavage site and a calcium-binding domain. In this data set we identified four robust evolutionary modules, one of which forms the minimal functional TIM barrel topology.The NPC1 protein is involved in the intracellular lipid metabolism coordinating sterol trafficking. NPC1 N-terminus is the first luminal domain which binds to cholesterol and its oxygenated derivatives. Our inferred dynamic modules in the protein NPC1 are also shown to match functional components of the protein related to the NPC1 disease. CONCLUSIONS: A domain compartmentalization can be found and described in correlation space. To our knowledge, there is no other method attempting to identify sub-domain architecture from the correlation among residues. Most attempts made focus on sequence motifs of protein-protein interactions, binding sites, or sequence conservancy. We were able to describe functional/structural sub-domain architecture related to key residues for starch cleavage, calcium, and chloride binding sites in the α-amylase, and sterol opening-defining modules and disease-related residues in the NPC1. We also described the evolutionary sub-domain architecture of the α-amylase catalytic domain, identifying the already reported minimum functional TIM barrel.

[Sporangia ontogeny and sporogenesis of the lycopodium Huperzia brevifolia (Lycopodiaceae) from the high mountains of Colombia]. / Ontogenia del esporangio y esporogénesis del licopodio Huperzia brevifolia (Lycopodiaceae) de las altas montañas de Colombia.

Huperzia brevifolia is one of the dominant species of the genus Huperzia living in paramos and superparamos from the Colombian Andes. A detailed study of the sporangium's ontogeny and sporogenesis was carried out using specimens collected at 4200m above sea level, in Parque Natural Nacional El Cocuy, Colombia. Small pieces of caulinar axis bearing sporangia were fixed, dehydrated, paraffin embedded, sectioned in a rotatory microtome, and stained using the common Safranin O-Fast Green technique; handmade cross sections were also made, stained with aqueous Toluidine Blue (TBO). The sporangia develops basipetally, a condition that allows observation of all the developmental stages taking place throughout the caulinar axis of adult plants. Each sporangium originates from a group of epidermal cells, axilar to the microphylls. These cells undergo active mitosis, and produce new external and internal cellular groups. The sporangium wall and the tapetum originate from the external group of cells, while the internal cellular group leads to the sporogenous tissue. Meiosis occur in the sporocytes and produce simultaneous types tetrads, each one giving rise four trilete spores, with foveolate ornamentation. During the sporangium ripening, the outermost layer of the wall develops anticlinally, and inner periclinal thickenings and the innermost one perform as a secretory tapetum, which persists until the spores are completely mature. All other cellular layers colapse.

The response to selection in Glycoside Hydrolase Family 13 structures: A comparative quantitative genetics approach.

The Glycoside Hydrolase Family 13 (GH13) is both evolutionarily diverse and relevant to many industrial applications. Its members hydrolyze starch into smaller carbohydrates and members of the family have been bioengineered to improve catalytic function under industrial environments. We introduce a framework to analyze the response to selection of GH13 protein structures given some phylogenetic and simulated dynamic information. We find that the TIM-barrel (a conserved protein fold consisting of eight α-helices and eight parallel ß-strands that alternate along the peptide backbone, common to all amylases) is not selectable since it is under purifying selection. We also show a method to rank important residues with higher inferred response to selection. These residues can be altered to effect change in properties. In this work, we define fitness as inferred thermodynamic stability. We show that under the developed framework, residues 112Y, 122K, 124D, 125W, and 126P are good candidates to increase the stability of the truncated α-amylase protein from Geobacillus thermoleovorans (PDB code: 4E2O; α-1,4-glucan-4-glucanohydrolase; EC 3.2.1.1). Overall, this paper demonstrates the feasibility of a framework for the analysis of protein structures for any other fitness landscape.

The Semantics of the Modular Architecture of Protein Structures.

Protein structures can be conceptualized as context-aware self-organizing systems. One of its emerging properties is a modular architecture. Such modular architecture has been identified as domains and defined as its units of evolution and function. However, this modular architecture is not exclusively defined by domains. Also, the definition of a domain is an ongoing debate. Here we propose differentiating structural, evolutionary and functional domains as distinct concepts. Defining domains or modules is confounded by diverse definitions of the concept, and also by other elements inherent to protein structures. An apparent hierarchy in protein structure architecture is one of these elements, where lower level interactions may create noise for the definition of higher levels. Diverse modularity-molding factors such as folding, function, and selection, can have a misleading effect when trying to define a given type of module. It is thus important to keep in mind this complexity when defining modularity in protein structures and interpreting the outcome modularity inference approaches.

Inferring meaningful communities from topology-constrained correlation networks.

Community structure detection is an important tool in graph analysis. This can be done, among other ways, by solving for the partition set which optimizes the modularity scores [Formula: see text]. Here it is shown that topological constraints in correlation graphs induce over-fragmentation of community structures. A refinement step to this optimization based on Linear Discriminant Analysis (LDA) and a statistical test for significance is proposed. In structured simulation constrained by topology, this novel approach performs better than the optimization of modularity alone. This method was also tested with two empirical datasets: the Roll-Call voting in the 110th US Senate constrained by geographic adjacency, and a biological dataset of 135 protein structures constrained by inter-residue contacts. The former dataset showed sub-structures in the communities that revealed a regional bias in the votes which transcend party affiliations. This is an interesting pattern given that the 110th Legislature was assumed to be a highly polarized government. The [Formula: see text]-amylase catalytic domain dataset (biological dataset) was analyzed with and without topological constraints (inter-residue contacts). The results without topological constraints showed differences with the topology constrained one, but the LDA filtering did not change the outcome of the latter. This suggests that the LDA filtering is a robust way to solve the possible over-fragmentation when present, and that this method will not affect the results where there is no evidence of over-fragmentation.

Zoogeography of Elasmobranchs in the Colombian Pacific Ocean and Caribbean Sea

Para conocer los patrones zoogeográficos de los elasmobranquios marinos de Colombia, la riqueza de especies de Pacífico y Caribe y sus subáreas (Pacífico costero, Pacífico oceánico, Caribe costero y Caribe oceánico) fue analizada. Las áreas compartieron 10 familias, 10 géneros y 16 especies de tiburones y ocho familias, tres géneros y cuatro especies de batoideos. Carcharhinidae tuvo la mayor contribución a la riqueza de tiburones mientras que Rajidae y Urotrygonidae tuvieron la mayor contribución a la riqueza de batoideos en el Caribe y el Pacífico, respectivamente. La mayoría de los elasmobranquios estuvieron asociados con hábitats bénticos y costeros. El análisis de similitud permitió la identificación de cinco grupos de familias que caracterizan la riqueza de elasmobranquios en ambas áreas. La diversidad beta indicó que el mayor recambio de especies se produjo entre el Pacífico costero y las dos subáreas del Caribe. La diferencia en la riqueza y composición de especies entre las áreas puede ser debida a eventos vicariantes tales como el surgimiento del Istmo de Panamá. Es poco probable que la diversidad de elasmobranquios en Colombia se originara de un único evento de colonización. Eventos locales de diversificación/especiación, dispersión desde las regiones templadas de América, del Pacífico y del Atlántico son orígenes posibles que no se excluyen entre sí.

In order to investigate zoogeographical patterns of the marine elasmobranch species of Colombia, species richness of the Pacific and Caribbean and their subareas (Coastal Pacific, Oceanic Pacific, Coastal Caribbean, Oceanic Caribbean) was analyzed. The areas shared 10 families, 10 genera and 16 species of sharks, and eight families, three genera and four species of batoids. Carcharhinidae had the highest contribution to shark richness, whereas Rajidae and Urotrygonidae had the greatest contribution to batoid richness in the Caribbean and Pacific, respectively. Most elasmobranchs were associated with benthic and coastal habitats. The similarity analysis allowed the identification of five groups of families, which characterize the elasmobranch richness in both areas. Beta diversity indicated that most species turnover occurred between the Coastal Pacific and the two Caribbean subareas. The difference in species richness and composition between areas may be due to vicariant events such as the emergence of the Isthmus of Panama. It is unlikely that the Colombian elasmobranch diversity originated from a single colonization event. Local diversification/speciation, dispersal from the non-tropical regions of the Americas, a Pacific dispersion and an Atlantic dispersion are origin possibilities without any of them excluding the others.

Ontogenia del esporangio y esporogénesis del licopodio Huperzia brevifolia (Lycopodiaceae) de las altas montañas de Colombia

Sporangia ontogeny and sporogenesis of the lycopodium Huperzia brevifolia (Lycopodiaceae) from the high mountains of Colombia. Huperzia brevifolia is one of the dominant species of the genus Huperzia living in paramos and superparamos from the Colombian Andes. A detailed study of the sporangium’s ontogeny and sporogenesis was carried out using specimens collected at 4200m above sea level, in Parque Natural Nacional El Cocuy, Colombia. Small pieces of caulinar axis bearing sporangia were fixed, dehydrated, paraffin embedded, sectioned in a rotatory microtome, and stained using the common Safranin O-Fast Green technique; handmade cross sections were also made, stained with aqueous Toluidine Blue (TBO). The sporangia develops basipetally, a condition that allows observation of all the developmental stages taking place throughout the caulinar axis of adult plants. Each sporangium originates from a group of epidermal cells, axilar to the microphylls. These cells undergo active mitosis, and produce new external and internal cellular groups. The sporangium wall and the tapetum originate from the external group of cells, while the internal cellular group leads to the sporogenous tissue. Meiosis occur in the sporocytes and produce simultaneous types tetrads, each one giving rise four trilete spores, with foveolate ornamentation. During the sporangium ripening, the outermost layer of the wall develops anticlinally, and inner periclinal thickenings and the innermost one perform as a secretory tapetum, which persists until the spores are completely mature. All other cellular layers colapse. Rev. Biol. Trop. 57 (4): 1141-1152. Epub 2009 December 01.

Se describe la ontogenia y la esporogénesis en H. brevifolia, en material recolectado en el Parque Nacional Natural El Cocuy (Boyacá-Colombia) a 4200m de altitud. Los esporangios se desarrollan de forma basípeta sobre el eje caulinar: los iniciales y juveniles se localizan en el ápice y los adultos a maduros, en la base. El desarrollo se inicia a partir de un grupo de células epidérmicas localizadas en las axilas que forman los microfilos con el eje caulinar. Estas células se dividen activamente por mitosis formando una masa celular externa y otra interna. La primera da origen a la pared del esporangio, de varios estratos celulares; de éstos, el estrato externo desarrolla engrosamientos en las paredes anticlinales y en la periclinal interna. El estrato celular interno se diferencia para formar el tapete secretor. Los demás estratos celulares de la pared se degradan durante la maduración del esporangio. La masa celular interna da origen al tejido esporógeno que forma los esporocitos, que experimentan la meiosis I hasta la etapa de díada. La meiosis II concluye con la formación de tétradas, constituidas por esporas en disposición tetraédrica. Las esporas son foveoladas con abertura trilete y son liberadas del esporangio a través de la dehiscencia.