| Comparative Genomics and Molecular Evolution |
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GrantsMolecular evolution of a neo-Y chromosomeBiotechnology and Biological Sciences Research Council (BBRSC), Reino Unido. Participants: Carolina Bartolomé Husson e Brian Charlesworth(IP) (Edinburgh University, UK). Description: The lack of recombination on the Y chromosome is responsible of its nearly complete degeneration. To know which evolutionary forces are involved in the accumulation of repetitive sequences and the inactivity of most of its genes, we use Drosophila miranda as a model; this species shows a recently formed Y chromosome (neo-Y) whose study allows to know how chromosomal degeneration is produced at intermediate stages of the process. The main objective of this project is to describe the molecular evolution of the neo-sex chromosomes by the comparative analysis of sequences of genes linked to these chromosomes, and to the X chromosome and autosomes, in several species of Drosophila (D. miranda, D. pseudoobscura y D. affinis). Genomic study of the evolutionary dynamics of mobile elements of Drosophila Ministerio de Educación y Ciencia. Participants: Xulio Maside (IP), Carolina Bartolomé Husson e Brian Charlesworth (Edinburgh University, UK). To comprehend the structure, organization and function of the genomes, we need to understand the underlying evolutionary processes that shape them. Transposable elements (TEs) are an essential component of the genomes of most organisms, and their presence is associated with many important functional and structural properties of the genomes. We plan to combine population genetics analysis tools with bioinformatics data mining, to address two questions that are central to our understanding of the natural history of TEs and their interactions with the host genomes: to obtain an estimate of the frequency of horizontal transfer, and to estimate the genomic transposition rate of Drosophila TEs. The first objective would provide an explanation for their presence in the genomes of most organisms, and their long-term persistence. The second focuses on their interactions with the host genomes, and their role as mutagenic agents. To do this, we shall: (i) use bioinformatics tools to search for all TEs on the genomic sequences of five Drosophila species, carefully chosen according to their almost optimal phylogenetic relationships for this purpose, and (ii) compare the patterns of diversity, distribution and divergence of TEs with those of nuclear genes from all species. (iii) We will identify all retrotransposons with two recognisable LTRs, and (iv) compare the number of insertions of other TEs between the LTRs with the number of mutations accumulated on the LTR sequences. Comparative and functional análisis of the proteins 5 beta-progesterone and 5 alfa-progesterone Grant funded by: Generalitat valenciana. Participants: Isabel Gavidia (IP;Universidad de Valencia), Pedro Pérez-Bermúdez (Universidad de Valencia), Francisco Rodríguez-Trelles y Rosa Tarrío. Grant period: 2005-2007. Summary: Cardenolides are natural products obtained from different species of the genus Digitalis (Escrophulariaceae). Currently, they are the only safe inotropic drug for the oral treatment of congestive cardiac insufficiency and, like other products of medicinal interest, they can only be obtained from plants. The study of the enzymes and the isolation of the genes involved in the biosinthesys of secondary metabolites are the basis for the development of alternative strategies for the production of cardenolides. Cholesterol or different phytosterols have been proposed as the starting point of their biosynthetic route. The steps leading to the formation of progesterone are similar to those transforming cholesterol into steroid hormones in animals. However, the reduction of progesterone represents a divergent intersection point of different metabolic routes in animal and plants. In this reaction, progesterone is metabolized by double-bond stereospecific reductases producing the 5α or 5β derivates. The 5α reductase is structutally and functionally conserved in plants and animals. Yet, the purification and sequencing of 5β-progesterone yields a sequence which has hypothetical homologs in other plants, but not in animals. There are at least two hypothesis to explain this pattern: a) random quick divergence in absence of strong functional constraints, and b) evolutionary convergence. Distinguishing between these and other possible scenarios could help to understand the functional significance of this key enzyme in the synthesis of cardenolides. To this end, we are engaged in ascertaining the evolutionary history and rates of the gene(s) encoding this enzyme. Estudio de genes de baja penetrancia asociados al riesgo de desarrollar cáncer colorectal en humanos, identificados a partir de loci asociados con el desarrollo de la enfermedad en ratón Grant funded by: Mutua Madrileña. Participantes: Clara Ruiz Ponte (IP), Francisco Barros, Ángel Carracedo, Begoña Graña, Antonio Salas, Francisco Rodríguez-Trelles, Rosa Tarrío y Ana Vega. Grant period: 2005-2007. La hipótesis variante común\enfermedad común en trastornos psiquiátricos: identificación de polimorfismos funcionales en genes candidatos mediante detección de alelos sometidos a selección natural en la reciente historia evolutiva de la especie humana Grant funded by: FIS. Participants: Javier Costas (IP) y Rosa Tarrío. Grant period: 2005-2008. Identificación de SNPs de termoregulación para el desarrollo de marcadores genéticos de susceptibilidad al estrés térmico en humanos Grant funded by: FIS. Participants: Francisco Rodríguez-Trelles (IP) y Rosa Tarrío. Grant period: 2005-2008. Summary: Global climate warming associated rise in the frequency of increasingly long and severe heatwaves is seriously distressing Human Health. In the face of this hazard, Spanish public health care administrations are defining risk groups considering only physiological criteria, such as age and pathological state of the individuals. Development of genetic markers of thermal susceptibility to better evaluate health risks associated with increasing temperatures is urgently needed in order to articulate more efficient preventive strategies. The aim of this Proposal is to identify genetic variants of thermosusceptibility, and their prevalence in the Spanish population using SNPs –single nucleotide polymorphisms– in four steps: 1) construction of a database of candidate genes of thermoregulation; 2) identification of those candidate genes in the database that, according to the polymorphism data of allelic variants, exhibit a pattern of geographic differentiation suggestive of thermal adaptation; 3) genotyping of thermal adaptation tag SNPs in the Human Genome Diversity Panel CEPH; and 4) genotyping of tag SNPs exhibiting the clearest patterns of thermal adaptation in the CEPH Panel in samples from North, Central and Southern Spain, obtained from the Banco Nacional de ADN de Salamanca. |
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