Papel de la selección sexual post-cópula sobre la evolución de genes reproductivos en mamíferos

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Ciencias, Departamento de Biología Molecular. Fecha de lectura: 10-10-2014Se ha apreciado que las proteínas implicadas en reproducción evolucionan rápidamente en muchos grupos taxonómicos. En muchos casos, la rápida divergencia de estas proteínas es dirigida por la evolución adaptativa (selección positiva Darwiniana), lo que indica que los cambios fijados son beneficiosos para la reproducción. Para explicar la rápida evolución de las proteínas reproductivas, se han sugerido varias fuerzas evolutivas, incluyendo la selección post-cópula. La selección sexual post-cópula comprende procesos tales como la competición espermática, que es la competición entre los espermatozoides de dos o más machos por fecundar un óvulo. La competición espermática promueve la adaptación de diversos rasgos reproductivos con el fin de incrementar el éxito de fecundación. Se ha propuesto frecuentemente que los cambios adaptativos en rasgos reproductivos dirigidos por las fuerzas selectivas son el resultado de la rápida evolución de las proteínas reproductivas. Este trabajo se centra en el estudio de la evolución de las proteínas integrales del espermatozoide en roedores, con el objetivo de identificar proteínas que evolucionan bajo la influencia de la competición espermática. Los diferentes estudios realizados revelaron que las proteínas con un papel en la motilidad espermática y en la interacción espermatozoide-óvulo muestran una mayor incidencia de evolución adaptativa, indicando que las fuerzas selectivas que actúan sobre el espermatozoide tienen un mayor impacto sobre estos dos procesos. Una proteína implicada en la regulación de la motilidad del espermatozoide, Catsper1, contiene un dominio intracelular que presenta una elevada tasa de inserciones y deleciones. Esta variación en longitud está promovida por selección positiva y la competición espermática favorece un acortamiento de esta región, lo cual se asocia con un incremento en la velocidad de natación del espermatozoide. Por otra parte, la proteína PKDREJ, que regula el transporte y la reacción acrosómica de los espermatozoides, presenta mayor divergencia en especies más promiscuas, mostrando que esta proteína puede ser importante para el éxito reproductivo en situaciones de competición espermática. Dos proteínas esenciales en la fusión de los gametos (Izumo1 en el espermatozoide y Cd9 en el óvulo) muestran selección positiva en dominios extracelulares implicados en la interacción con proteínas. Además, estos dos dominios están sujetos a un proceso de coevolución, sugiriendo que Izumo1 y Cd9 podrían tener una interacción directa durante la fecundación. Por último, los análisis de proteómica detectaron diferencias cuantitativas de proteínas del espermatozoide entre especies con diferentes niveles de competición espermática. Las especies de alta competición espermática presentan mayor abundancia de algunas proteínas con funciones importantes para el éxito reproductivo, revelando que la selección sexual puede promover cambios en la expresión de proteínas. Estos resultados dan evidencia del papel importante que tienen las fuerzas de selección sexual, y en concreto la competición espermática, en la evolución de las proteínas reproductivasIt has been appreciated that proteins involved in reproduction are rapidly evolving in many taxonomical groups. In many cases, the rapid divergence of these proteins is driven by adaptive evolution (positive Darwinian selection), which indicates that the fixed changes are beneficial to reproduction. To explain the rapid evolution of reproductive proteins, several evolutionary forces have been identified, including post-copulatory sexual selection. Post-copulatory sexual selection comprises several processes such as sperm competition, which is the competition between the sperm of two or more males to fertilize the ova. Sperm competition promotes the adaption of diverse reproductive traits to increase the fertilization success. It has often been proposed that adaptive changes in reproductive traits driven by selective forces are the result of the rapid evolution of reproductive proteins. This work focuses on studying the evolution of integral sperm proteins in rodents with the purpose of identifying proteins evolving under sperm competition. The different studies revealed that proteins with a role in sperm motility and sperm-egg interaction show a higher prevalence of adaptive evolution, indicating that the selective forces acting on spermatozoa have a higher impact on these two processes. A protein involved in the regulation of sperm motility, Catsper1, contains an intracellular domain showing an elevated rate of insertions and deletions. Length variation of this protein is promoted by positive selection, and sperm competition favors a shortening of this region, which is associated with increases in sperm swimming velocity. On the other hand, PKDREJ protein, which regulates sperm transport and acrosome reaction, shows higher divergence in more promiscuous species, revealing that this protein could be important for reproductive success under situations of sperm competition. Two essential proteins in gamete fusion (Izumo1 in the spermatozoon and Cd9 in the egg) show positive selection in the extracellular domains involved in protein interaction. In addition, these two domains are subjected to a coevolutionary process, suggesting that Izumo1 and Cd9 could have a direct interaction during fertilization. Finally, proteomic analyses detected quantitative differences in sperm proteins among species with different levels of sperm competition. High sperm competition species show higher abundance of some proteins with important functions for reproductive success, revealing that sexual selection is able to promote changes in protein expression. Altogether, these results give evidence that sexual selective forces, and in particular sperm competition, have an important role in the evolution of reproductive proteins

Evolution of protamine genes and changes in sperm head phenotype in rodents

Little is known about the genetic basis of evolutionary changes in sperm phenotype. Postcopulatory sexual selection is associated with differences in protamine gene sequences and promoters and is a powerful force acting on sperm form and function, although links between protamine evolution and sperm phenotype are scarce. Protamines are involved in sperm chromatin condensation, and protamine deficiency negatively affects sperm morphology and male fertility, thus suggesting that they are important for sperm design and function. We examined changes in protamine genes and sperm phenotype in rodents to understand the role of sexual selection on protamine evolution and sperm design. We performed a genotype-phenotype association study using root-to-tip dN/dS (nonsynonymous/ synonymous substitutions rate ratio) to account for evolutionary rates and phylogenetic generalized least squares analyses to compare genetic and morphometric data. Evolutionary rates of protamine 1 and the protamine 2 domain cleaved off during chromatin condensation correlated with head size and elongation. Protamine 1 exhibited restricted positive selection on some functional sites, which seemed sufficient to preserve its role in head design. The cleaved-protamine 2, whose relaxation is halted by sexual selection, seems to ensure small, elongated heads that would make sperm more competitive. No association existed between mature-protamine 2 and head phenotype, suggesting little involvement during chromatin condensation and a likely role maintaining the condensed state. Our results suggest that evolutionary changes in protamines could be related to complex developmental modifications in the sperm head. This represents an important step toward understanding the role of changes in gene coding sequences in the divergence of germ cell phenotype. © 2014 by the Society for the Study of Reproduction, Inc.Peer Reviewe

Análisis y reflexión de un proyecto interdisciplinar para la promoción del desplazamiento activo al centro escolar.

Hoy en día es cada vez más frecuente que la población infantil y adolescente dedique menos tiempo a la realización de actividad física, por ello, desde los centros escolares se está promoviendo, a través de proyectos interdisciplinares, el desplazamiento activo como herramienta para aumentar los niveles de actividad física entre estas edades. En este trabajo se analiza el proyecto “Ir al cole y volver a casa activamente” que se desarrolló en el centro escolar San Bernardo-Salesianos de Huesca en el curso escolar 2017-2018, se trata de un proyecto interdisciplinar de promoción de desplazamiento activo al centro escolar cuyo eje principal es la asignatura de educación física. Una vez finalizado el proyecto, se reflexiona acerca de una serie de categorías determinadas previamente y se constatan las cuestiones que han funcionado durante la puesta en marcha o las que no han funcionado y habría que mejorar de cara a otros años

Coevolution of positively selected IZUMO1 and CD9 in rodents: Evidence of interaction between gamete fusion proteins?

Proteins involved in sexual reproduction are known to evolve rapidly, often as the result of positive Darwinian selection, although the selective forces driving such adaptive changes are poorly understood. A process of coevolution between proteins in male and female gametes may promote rapid divergence of fertilization proteins. In the mouse, only two proteins have been shown so far to be essential for sperm-egg fusion, IZUMO1 in the sperm cell and CD9 in the egg. The role of these proteins has not been fully elucidated, and it has been suggested that they may act as fusogens, interacting in trans with proteins on the other cell, or regulators of fusogens through cis interactions. Here we analyze the evolution of IZUMO1 and CD9 in a group of rodent species. To assess possible protein interactions between IZUMO1 and CD9, we examined potential coevolution based on analyses of correlated evolutionary rates. We found evidence that both proteins evolve adaptively, with a more intense signal of positive selection in IZUMO1. In addition, our findings suggest that these proteins may have some form of interaction, although they have not been regarded as fusogens interacting directly with each other. The adaptive divergence of IZUMO1 and CD9 could influence reproductive compatibility, and, thus, these proteins may participate in the establishment of specific sperm-egg recognition systems. Further studies are required to uncover the role of IZUMO1 and CD9 during gamete fusion in order to understand the molecular basis of their coevolution, as other selective forces could also lead to general signatures of coevolution. © 2014 by the Society for the Study of Reproduction, Inc.Peer Reviewe

La economía del bien común.

The Common Good economy is a new economic model, proposed by Christian Felber in the year 2012. It is a new way of understanding the economy; taking into consideration social and human values. The following project aims to show a global vision of this theory, comparing it with ancient economic theories and, subsequently, to make known the impact it has had on the world and on our environment. With the balance and the matrix of the common good will check how the behaviour of enterprises is measured in this new model. This paper seeks to make known the novelty of the model, as well as the great impact it would have on the environment and in social inequalities.La economía del Bien Común es un nuevo modelo económico, propuesto por Christian Felber en el año 2010. Se trata de una nueva forma de entender la economía, tomando en consideración valores sociales y humanos. El siguiente trabajo pretende mostrar una visión global de esta teoría, comparándola con teorías económicas antiguas para, posteriormente, dar a conocer el impacto que ha tenido en el mundo y en nuestro entorno. Con el balance y la matriz del bien común se comprobará la forma en que se mide el comportamiento de las empresas en esta nueva propuesta. Con este trabajo se intenta dar a conocer lo novedoso del modelo, así como el gran impacto que tendría en el medioambiente y en las desigualdades sociales

Cultura tecnologica, teorie e prassi del progetto di architettura

La scuola madrileña pone da sempre grande attenzione al rapporto tra teoria e prassi del progetto. Le interviste ad alcuni suoi esponenti hanno lo scopo di comporre un dialogo a più voci che ponga l’attenzione sul tema del progetto di architettura come azione al tempo stesso intellettuale e tecnica, fin dalla sua concezione legato alla sua costruibilità e fondato su una profonda sapienza costruttiva e tecnologica. Jesús Aparicio, Jesús Donaire, Alberto Campo Baeza, Ignacio Vicens, architetti e docenti formati e operanti alla ETSAM, rappresentano le voci di tale dialogo; o meglio la voce, con i toni delle diverse generazioni, di un unico canto corale.The Madrid school has always paid close attention to the relationship between theory and practice of design. These interviews, with some of the exponents of the school, aim at composing a plurivocal dialogue, focusing on the theme of architectural design as -simultaneously- intellectual and technical action, bound up, from its conception, to its buildability, and founded on a deep knowledge of construction and technology. Jesús Aparicio, Jesús Donaire, Alberto Campo Baeza and Ignacio Vicens, architects and professors trained and operating at the Escuela Técnica Superior de Arquitectura de Madrid (ETSAM), are the voices of this dialogue; or better the voice of a single choral work, compose

Effects of environmental and physiological covariates on sex differences in unconditioned and conditioned anxiety and fear in a large sample of genetically heterogeneous (N/Nih-HS) rats

Physiological and environmental variables, or covariates, can account for an important portion of the variability observed in behavioural/physiological results from different laboratories even when using the same type of animals and phenotyping procedures. We present the results of a behavioural study with a sample of 1456 genetically heterogeneous N/Nih-HS rats, including males and females, which are part of a larger genome-wide fine-mapping QTL (Quantitative Trait Loci) study. N/Nih-HS rats have been derived from 8 inbred strains and provide very small distance between genetic recombinations, which makes them a unique tool for fine-mapping QTL studies. The behavioural test battery comprised the elevated zero-maze test for anxiety, novel-cage (open-field like) activity, two-way active avoidance acquisition (related to conditioned anxiety) and context-conditioned freezing (i.e. classically conditioned fear). Using factorial analyses of variance (ANOVAs) we aimed to analyse sex differences in anxiety and fear in this N/Nih-HS rat sample, as well as to assess the effects of (and interactions with) other independent factors, such as batch, season, coat colour and experimenter. Body weight was taken as a quantitative covariate and analysed by covariance analysis (ANCOVA). Obliquely-rotated factor analyses were also performed separately for each sex, in order to evaluate associations among the most relevant variables from each behavioural test and the common dimensions (i.e. factors) underlying the different behavioural responses. ANOVA analyses showed a consistent pattern of sex effects, with females showing less signs of anxiety and fear than males across all tests. There were also significant main effects of batch, season, colour and experimenter on almost all behavioural variables, as well as "sex × batch", "sex × season" and "sex × experimenter" interactions. Body weight showed significant effects in the ANCOVAs of most behavioural measures, but sex effects were still present in spite of (and after controlling for) these "body weight" effects. Factor analyses of relevant variables from each test showed a two-fold factor structure in both sexes, with the first factor mainly representing anxiety and conditioned fear in males, while in females the first factor was dominated by loadings of activity measures. Thus, besides showing consistent sex differences in anxiety-, fear- and activity-related responses in N/Nih-HS rats, the present study shows that females' behaviour is predominantly influenced by activity while males are more influenced by anxiety. Moreover, the results point out that, besides "sex" effects, physiological variables such as colour and body weight, and environmental factors as batch/season or "experimenter", have to be taken into account in both behavioural and quantitative genetic studies because of their demonstrated influences on phenotypic outcomes

Safety and vaccine-induced HIV-1 immune responses in healthy volunteers following a late MVA-B boost 4 years after the last immunization

Background: We have previously shown that an HIV vaccine regimen including three doses of HIV-modified vaccinia virus Ankara vector expressing HIV-1 antigens from clade B (MVA-B) was safe and elicited moderate and durable (1 year) T-cell and antibody responses in 75% and 95% of HIV-negative volunteers (n = 24), respectively (RISVAC02 study). Here, we describe the long-term durability of vaccine-induced responses and the safety and immunogenicity of an additional MVA-B boost. Methods: 13 volunteers from the RISVAC02 trial were recruited to receive a fourth dose of MVA-B 4 years after the last immunization. End-points were safety, cellular and humoral immune responses to HIV-1 and vector antigens assessed by ELISPOT, intracellular cytokine staining (ICS) and ELISA performed before and 2, 4 and 12 weeks after receiving the boost. Results: Volunteers reported 64 adverse events (AEs), although none was a vaccine-related serious AE. After 4 years from the 1st dose of the vaccine, only 2 volunteers maintained low HIV-specific T-cell responses. After the late MVA-B boost, a modest increase in IFN-γ T-cell responses, mainly directed against Env, was detected by ELISPOT in 5/13 (38%) volunteers. ICS confirmed similar results with 45% of volunteers showing that CD4+ T-cell responses were mainly directed against Env, whereas CD8+ T cell-responses were similarly distributed against Env, Gag and GPN. In terms of antibody responses, 23.1% of the vaccinees had detectable Env-specific binding antibodies 4 years after the last MVA-B immunization with a mean titer of 96.5. The late MVA-B boost significantly improved both the response rate (92.3%) and the magnitude of the systemic binding antibodies to gp120 (mean titer of 11460). HIV-1 neutralizing antibodies were also enhanced and detected in 77% of volunteers. Moreover, MVA vector-specific T cell and antibody responses were boosted in 80% and 100% of volunteers respectively. Conclusions: One boost of MVA-B four years after receiving 3 doses of the same vaccine was safe, induced moderate increases in HIV-specific T cell responses in 38% of volunteers but significantly boosted the binding and neutralizing antibody responses to HIV-1 and to the MVA vector