Evolution of the eyes of vipers with and without infrared-sensing pit organs

We examined lens and brille transmittance, photoreceptors, visual pigments, and visual opsin gene sequences of viperid snakes with and without infrared-sensing pit organs. Ocular media transmittance is high in both groups. Contrary to previous reports, small as well as large single cones occur in pit vipers. Non-pit vipers differ from pit vipers in having a twotiered retina, but few taxa have been examined for this poorly understood feature. All vipers sampled express rh1, sws1 and lws visual opsin genes. Opsin spectral tuning varies but not in accordance with the presence/absence of pit organs, and not always as predicted from gene sequences. The visual opsin genes were generally under purifying selection, with positive selection at spectral tuning amino acids in RH1 and SWS1 opsins, and at retinal pocket stabilization sites in RH1 or LWS (and without substantial differences between pit and nonpit vipers). Lack of evidence for sensory trade-off between viperid eyes (in the aspects examined) and pit organs might be explained by the high degree of neural integration of vision and infrared detection; the latter representing an elaboration of an existing sense with addition of a novel sense organ, rather than involving the evolution of a wholly novel sensory system

Evolutionary and structural aspects of Solanaceae RNases T2

Plant RNases T2 are involved in several physiological and developmental processes, including inorganic phosphate starvation, senescence, wounding, defense against pathogens, and the self-incompatibility system. Solanaceae RNases form three main clades, one composed exclusively of S-RNases and two that include S-like RNases. We identified several positively selected amino acids located in highly flexible regions of these molecules, mainly close to the B1 and B2 substrate-binding sites in S-like RNases and the hypervariable regions of S-RNases. These differences between S- and S-like RNases in the flexibility of amino acids in substrate-binding regions are essential to understand the RNA-binding process. For example, in the S-like RNase NT, two positively selected amino acid residues (Tyr156 and Asn134) are located at the most flexible sites on the molecular surface. RNase NT is induced in response to tobacco mosaic virus infection; these sites may thus be regions of interaction with pathogen proteins or viral RNA. Differential selective pressures acting on plant ribonucleases have increased amino acid variability and, consequently, structural differences within and among S-like RNases and S-RNases that seem to be essential for these proteins play different functions

Bayesian machine learning methods for predicting protein-peptide interactions and detecting mosaic structures in DNA sequences alignments

Short well-defined domains known as peptide recognition modules (PRMs) regulate many important protein-protein interactions involved in the formation of macromolecular complexes and biochemical pathways. High-throughput experiments like yeast two-hybrid and phage display are expensive and intrinsically noisy, therefore it would be desirable to target informative interactions and pursue in silico approaches. We propose a probabilistic discriminative approach for predicting PRM-mediated protein-protein interactions from sequence data. The model suffered from over-fitting, so Laplacian regularisation was found to be important in achieving a reasonable generalisation performance. A hybrid approach yielded the best performance, where the binding site motifs were initialised with the predictions of a generative model. We also propose another discriminative model which can be applied to all sequences present in the organism at a significantly lower computational cost. This is due to its additional assumption that the underlying binding sites tend to be similar.It is difficult to distinguish between the binding site motifs of the PRM due to the small number of instances of each binding site motif. However, closely related species are expected to share similar binding sites, which would be expected to be highly conserved. We investigated rate variation along DNA sequence alignments, modelling confounding effects such as recombination. Traditional approaches to phylogenetic inference assume that a single phylogenetic tree can represent the relationships and divergences between the taxa. However, taxa sequences exhibit varying levels of conservation, e.g. due to regulatory elements and active binding sites, and certain bacteria and viruses undergo interspecific recombination. We propose a phylogenetic factorial hidden Markov model to infer recombination and rate variation. We examined the performance of our model and inference scheme on various synthetic alignments, and compared it to state of the art breakpoint models. We investigated three DNA sequence alignments: one of maize actin genes, one bacterial (Neisseria), and the other of HIV-1. Inference is carried out in the Bayesian framework, using Reversible Jump Markov Chain Monte Carlo

Estructura genética de árboles forestales en regiones de alta biodiversidad a diferentes escalas espaciales

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Ciencias Biológicas, Departamento de Genética, leída el 09-05-2014. Tesis formato europeo (Compendio de artículos)Depto. de Genética, Fisiología y MicrobiologíaFac. de Ciencias BiológicasTRUEunpu

Lineage tracing of normal human development and childhood cancers

From fertilisation onwards, the cells of the human body continuously experience damage to their genome, either from intrinsic causes or from exposure to mutagens. While the vast majority of DNA damage is repaired and the genome is replicated with extremely high fidelity, cells steadily acquire single nucleotide variants throughout life. Since cells pass these genetic changes on to their descendants, mutations shared between any two cells therefore imply a shared developmental path. In essence, these somatic mutations connect all cells together into one large phylogenetic tree of human development with the zygote at the root. Reconstructing phylogenies of human development requires readouts of somatic mutations present in single cells. Recently, low-input whole-genome sequencing following laser-capture microdissection has allowed us to reliably call somatic mutations in distinct single-cell derived physiological units, such as colonic crypts and endometrial glands, while retaining spatial information on a microscopic level. In this way, I reconstructed large-scale phylogenies of cells from many different organs of three individuals. These phylogenetic trees recapitulate the early stages of embryonic development and asymmetric cell allocation in the blastocyst, as well as later clonal expansions such as benign prostatic hyperplasia and neoplastic polyp formation. In a similar way, I also used somatic mutations to investigate the emergence of paediatric cancer, which is thought to be closely linked to aberrations in development. In the context of phylogenetic analyses of tumours, mutations shared between childhood cancers and different normal tissues can shed light on the embryonic lineage of tumours and may reveal the precise juncture at which tumours began to form. Accordingly, I studied the origin of Wilms tumour, the most common childhood cancer of the kidney. I discovered that these tumours often arise from large tissue-resident precursor clones residing in the normal kidney. These embryonal precursors represent an early clonal expansion driven by H19 hypermethylation. Lastly, using somatic mutations I discovered that the human placenta is made up of large clonal patches of closely related trophoblast cells. Comparing early embryonic mutations between placental lineages and umbilical cord DNA, which is derived from the inner cell mass, revealed that in approximately half of the cases, a trophectodermal lineage shares no somatic mutations with the umbilical cord. Furthermore, in a quarter of cases, the umbilical cord is entirely derived from a progenitor later than the zygote. This indicates a natural early segregation between these lineages and a pathway to generate confined placental mosaicism. This dissertation as a whole provides a new framework to study normal and aberrant human development from whole-genome sequencing. The ability to reconstruct developmental lineages retrospectively can answer fundamental questions about human development and carcinogenesis