Phenotypic plasticity can facilitate adaptive evolution in gene regulatory circuits

BACKGROUND: Many important evolutionary adaptations originate in the modification of gene regulatory circuits to produce new gene activity phenotypes. How do evolving populations sift through an astronomical number of circuits to find circuits with new adaptive phenotypes? The answer may often involve phenotypic plasticity. Phenotypic plasticity allows a genotype to produce different - alternative - phenotypes after non-genetic perturbations that include gene expression noise, environmental change, or epigenetic modification. RESULTS: We here analyze a well-studied model of gene regulatory circuits. A circuit's genotype encodes the regulatory interactions among circuit genes, and its phenotype corresponds to a stable gene activity pattern the circuit forms. For this model, we study how genotypes are arranged in genotype space, where the distance between two genotypes reflects the number of regulatory mutations that set those genotypes apart. Specifically, we address whether this arrangement favors adaptive evolution mediated by plasticity. We find that plasticity facilitates the origin of genotypes that produce a new phenotype in response to non-genetic perturbations. We also find that selection can then stabilize the new phenotype genetically, allowing it to become a circuit's dominant gene expression phenotype. These are generic properties of the circuits we study here. CONCLUSIONS: Taken together, our observations suggest that phenotypic plasticity frequently facilitates the evolution of novel beneficial gene activity patterns in gene regulatory circuits

Interlinked nonlinear subnetworks underlie the formation of robust cellular patterns in Arabidopsis epidermis: a dynamic spatial model

<p>Abstract</p> <p>Background</p> <p>Dynamical models are instrumental for exploring the way information required to generate robust developmental patterns arises from complex interactions among genetic and non-genetic factors. We address this fundamental issue of developmental biology studying the leaf and root epidermis of <it>Arabidopsis</it>. We propose an experimentally-grounded model of gene regulatory networks (GRNs) that are coupled by protein diffusion and comprise a meta-GRN implemented on cellularised domains.</p> <p>Results</p> <p>Steady states of the meta-GRN model correspond to gene expression profiles typical of hair and non-hair epidermal cells. The simulations also render spatial patterns that match the cellular arrangements observed in root and leaf epidermis. As in actual plants, such patterns are robust in the face of diverse perturbations. We validated the model by checking that it also reproduced the patterns of reported mutants. The meta-GRN model shows that interlinked sub-networks contribute redundantly to the formation of robust hair patterns and permits to advance novel and testable predictions regarding the effect of cell shape, signalling pathways and additional gene interactions affecting spatial cell-patterning.</p> <p>Conclusion</p> <p>The spatial meta-GRN model integrates available experimental data and contributes to further understanding of the <it>Arabidopsis </it>epidermal system. It also provides a systems biology framework to explore the interplay among sub-networks of a GRN, cell-to-cell communication, cell shape and domain traits, which could help understanding of general aspects of patterning processes. For instance, our model suggests that the information needed for cell fate determination emerges from dynamic processes that depend upon molecular components inside and outside differentiating cells, suggesting that the classical distinction of lineage <it>versus </it>positional cell differentiation may be instrumental but rather artificial. It also suggests that interlinkage of nonlinear and redundant sub-networks in larger networks is important for pattern robustness. Pursuing dynamic analyses of larger (genomic) coupled networks is still not possible. A repertoire of well-characterised regulatory modules, like the one presented here, will, however, help to uncover general principles of the patterning-associated networks, as well as the peculiarities that originate diversity.</p

Floral Morphogenesis: Stochastic Explorations of a Gene Network Epigenetic Landscape

In contrast to the classical view of development as a preprogrammed and deterministic process, recent studies have demonstrated that stochastic perturbations of highly non-linear systems may underlie the emergence and stability of biological patterns. Herein, we address the question of whether noise contributes to the generation of the stereotypical temporal pattern in gene expression during flower development. We modeled the regulatory network of organ identity genes in the Arabidopsis thaliana flower as a stochastic system. This network has previously been shown to converge to ten fixed-point attractors, each with gene expression arrays that characterize inflorescence cells and primordial cells of sepals, petals, stamens, and carpels. The network used is binary, and the logical rules that govern its dynamics are grounded in experimental evidence. We introduced different levels of uncertainty in the updating rules of the network. Interestingly, for a level of noise of around 0.5–10%, the system exhibited a sequence of transitions among attractors that mimics the sequence of gene activation configurations observed in real flowers. We also implemented the gene regulatory network as a continuous system using the Glass model of differential equations, that can be considered as a first approximation of kinetic-reaction equations, but which are not necessarily equivalent to the Boolean model. Interestingly, the Glass dynamics recover a temporal sequence of attractors, that is qualitatively similar, although not identical, to that obtained using the Boolean model. Thus, time ordering in the emergence of cell-fate patterns is not an artifact of synchronous updating in the Boolean model. Therefore, our model provides a novel explanation for the emergence and robustness of the ubiquitous temporal pattern of floral organ specification. It also constitutes a new approach to understanding morphogenesis, providing predictions on the population dynamics of cells with different genetic configurations during development

On the basic computational structure of gene regulatory networks

Gene regulatory networks constitute the first layer of the cellular computation for cell adaptation and surveillance. In these webs, a set of causal relations is built up from thousands of interactions between transcription factors and their target genes. The large size of these webs and their entangled nature make difficult to achieve a global view of their internal organisation. Here, this problem has been addressed through a comparative study for {\em Escherichia coli}, {\em Bacillus subtilis} and {\em Saccharomyces cerevisiae} gene regulatory networks. We extract the minimal core of causal relations, uncovering the hierarchical and modular organisation from a novel dynamical/causal perspective. Our results reveal a marked top-down hierarchy containing several small dynamical modules for \textit{E. coli} and \textit{B. subtilis}. Conversely, the yeast network displays a single but large dynamical module in the middle of a bow-tie structure. We found that these dynamical modules capture the relevant wiring among both common and organism-specific biological functions such as transcription initiation, metabolic control, signal transduction, response to stress, sporulation and cell cycle. Functional and topological results suggest that two fundamentally different forms of logic organisation may have evolved in bacteria and yeast.Comment: This article is published at Molecular Biosystems, Please cite as: Carlos Rodriguez-Caso, Bernat Corominas-Murtra and Ricard V. Sole. Mol. BioSyst., 2009, 5 pp 1617--171

Epidemiología molecular y análisis filogenético de la infección por el virus del papiloma humano en mujeres con lesiones cervicales y cáncer en la región litoral del Ecuador

The aim of the present study was to gather information regarding the molecular epidemiology of Human papillomavirus (HPV) and related risk factors in a group of women with low- and high-grade cervical lesions and cancer from the coastal region of Ecuador. In addition, we studied the evolution of HPV variants from the most prevalent types and provided a temporal framework for their emergence, which may help to trace the source of dissemination within the region. We analyzed 166 samples, including 57 CIN1, 95 CIN2/3 and 14 cancer cases. HPV detection and typing was done by PCR-sequencing (MY09/MY11). HPV variants and estimation of the time to most recent common ancestor (tMRCA) was assessed through phylogeny and coalescence analysis. HPV DNA was found in 54.4% of CIN1, 74.7% of CIN2/3 and 78.6% of cancer samples. HPV16 (38.9%) and HPV58 (19.5%) were the most prevalent types. Risk factors for the development of cervical lesions/cancer were the following: three or more pregnancies (OR = 4.3), HPV infection (OR = 3.7 for high-risk types; OR = 3.5 for HPV16), among others. With regard to HPV evolution, HPV16 isolates belonged to lineages A (69%) and D (31%) whereas HPV58 isolates belonged only to lineage A. The period of emergence of HPV16 was in association with human populations (tMRCA = 91. 052 years for HPV16A and 27. 000 years for HPV16D), whereas HPV58A preceded Homo sapiens evolution (322. 257 years). This study provides novel data on HPV epidemiology and evolution in Ecuador, which will be fundamental in the vaccine era.Fil: Bedoya Pilozo, Cesar H.. Escuela Superior Politécnica del Litoral; Ecuador. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: Medina Magües, Lex G.. Escuela Superior Politécnica del Litoral; EcuadorFil: Espinosa García, Maylen. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: Sánchez, Martha. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: Parrales Valdiviezo, Johanna V.. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: Molina, Denisse. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: Ibarra, María A.. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: Quimis Ponce, María. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: España, Karool. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: Párraga Macias, Karla E.. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: Cajas Flores, Nancy V.. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: Solon, Orlando A.. Instituto Nacional de Investigaciones en Salud Pública; Ecuador. Universidad Agraria del Ecuador; EcuadorFil: Robalino Penaherrera, Jorge A.. Instituto Nacional de Investigaciones en Salud Pública; EcuadorFil: Chedraui, Peter. Hospital Gineco-Obstétrico Enrique C. Sotomayor; EcuadorFil: Escobar, Saul. Universidad Católica de Guayaquil; EcuadorFil: Loja Chango, Rita D.. Universidad Católica de Guayaquil; EcuadorFil: Ramirez Morán, Cecibel. Universidad Católica de Guayaquil; EcuadorFil: Espinoza Caicedo, Jasson. Universidad Católica de Guayaquil; EcuadorFil: Sánchez Giler, Sunny. Universidad Especialidades Espíritu Santo. Facultad de Ciencias Médicas; EcuadorFil: Limia, Celia M.. Instituto de Medicina Tropical Pedro Kouri; CubaFil: Alemán, Yoan. Instituto de Medicina Tropical Pedro Kouri; CubaFil: Soto, Yudira. Instituto de Medicina Tropical Pedro Kouri; CubaFil: Kouri, Vivian. Instituto de Medicina Tropical Pedro Kouri; CubaFil: Culasso, Andrés Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología. Cátedra de Virología; ArgentinaFil: Badano, Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Secretaría de Educación Superior, Ciencia, Tecnología e Innovación; Ecuador. Universidad Nacional de Misiones. Facultad de Ciencias Exactas, Químicas y Naturales. Laboratorio de Biología Molecular Aplicada; Argentin

Specialization Can Drive the Evolution of Modularity

Organismal development and many cell biological processes are organized in a modular fashion, where regulatory molecules form groups with many interactions within a group and few interactions between groups. Thus, the activity of elements within a module depends little on elements outside of it. Modularity facilitates the production of heritable variation and of evolutionary innovations. There is no consensus on how modularity might evolve, especially for modules in development. We show that modularity can increase in gene regulatory networks as a byproduct of specialization in gene activity. Such specialization occurs after gene regulatory networks are selected to produce new gene activity patterns that appear in a specific body structure or under a specific environmental condition. Modules that arise after specialization in gene activity comprise genes that show concerted changes in gene activities. This and other observations suggest that modularity evolves because it decreases interference between different groups of genes. Our work can explain the appearance and maintenance of modularity through a mechanism that is not contingent on environmental change. We also show how modularity can facilitate co-option, the utilization of existing gene activity to build new gene activity patterns, a frequent feature of evolutionary innovations

La plaza pública

1 archivo PDF (269 páginas) : incluye ilustraciones"El interés central de la publicación radica en discutir sobre la crisis de la “ciudad” o de la “urbanidad” que se manifiesta con más fuerza en el espacio público, ya que actualmente existen formas que obstaculizan el contacto; esto es, la relación entre personas y entre actividades dentro del espacio urbano. Algunos autores han insinuado que el espacio público está condenado a la irrelevancia, de manera que incluso plantean la existencia de los llamados “no lugares” que no están vinculados a algún sitio específico. ...