Research Group: Genomics, Bioinformatics and Evolutionary Biology (SGR Generalitat Catalunya)


     Coordinator: Dr. Alfredo Ruiz           


Our research 

Evolutionary Biology is the common denominator of our research, a complex historical process that accounts for the current Biodiversity on earth. We seek to understand the mechanisms that generate diversity patterns at several levels: geographical, phenotypical, chromosomal and nucleotide levels. The genetic basis of phenotypic diversity and evolution, framed within the study of genome variation, is the nucleus of our reseach. Our experimental work makes use of two different species as model systems, Drosophila and humans. We combine methods of genomics, genetics, bioinformatics and evolutionary biology to study this central problem from different points of view. This is done through a series of interrelated objectives dealing with fundamental questions in biology that have implications in many diverse fields, from basic research to biomedicine. Our multidisciplinary team includes researchers with diverse expertise that use different but complementary approaches: from experimental and field work to bioinformatics and modelization. We are engaged in projects of comparative genomics in Drosophila, adaptation of Drosophila populations to global climate change, genome-wide analyses of nucleotide and structural variability in a large set of Drosophila lines, modelization of the genotype-phenotype map, and functional and evolutionary impact of inversions in the human genome. 


1. Comparative genomics of host adaptation in cactophilic Drosophila. Drosophila is an excellent model for studies of comparative genomics as shown by the previous evolutionary analysis of 12 genomes by a consortium that included several members of our group. The cactophilic species of the repleta group, including D. buzzatii and D. mojavensis, have a well defined ecology which is an additional advantage for the investigation of the genetic basis of ecological adaptation. The central objective of this project is the comparison of the genomes and transcriptomes of D. buzzatii and D. mojavensis, two species inhabiting different geographical areas and host plants. This comparison will provide information on genetic changes experienced by these two species to adapt to their respective ecological niches, including the cactus host. In addition, the genomes of these two cactophilic species will be compared with those of two other non-cactophilic species of the same subgenus (D. virilis and D. grimshawi) to provide information on the genetic changes necessary for adaptation to the cactophilic niche. In collaboration with the Centre de Recerca en Agrigenomica (CRAG), the Centre Nacional d'Anàlisi Genòmica (CNAG) and the Plataforma Bioinformatica UAB-Hospitals (UAB PB -H) we have already sequenced the entire genome of D. buzzatii using the Roche 454 and Illumina sequencing platforms. The assembly comprises 826 scaffolds >3 kb long and a total of 161.5 Mb. We have also annotated all protein-coding genes (PCG) and transposable elements (TE). We seek to complete this project and carry out the following evolutionary analyses in collaboration with our international partners. (i) We will compare ortholog PCG between the four Drosophila subgenus species (D. buzzatii, D. mojavensis, D.virilis and D. grimshawi) to analyze molecular evolution in a phylogenetic framework and identify candidate genes under positive selection and orphan (lineage-specific) PCG. (ii) All copies of TE present in the genome of D. buzzatii will be annotated and classified to compare the abundance and chromosomal distribution of the different classes with D.mojavensis and other species of Drosophila. The evolutionary dynamics of selected TE families will be analyzed by phylogenetic methods. (iii) We will characterize the developmental transcriptomes of D. buzzatii and D. mojavensisgenerating RNA sequences from five life-cycle stages (eggs, embryos, larvae, pupae, males and females). This will allow comparisons D. buzzatii strains (to test the effect of chromosomal inversions) and also between species. PhD People of the GBBE involved: A. Ruiz, A. Delprat, M. Puig, A. Barbadilla.


2. Spatiotemporal distribution patterns of D. subobscura inversion polymorphism in relation to ongoing climate warming. The study of chromosomal inversion polymorphisms in the genus Drosophila has a long and venerable tradition in population genetics. In the case of D. subobscura, its rich inversion polymorphism was initially supposed to be invariant, or to vary erratically with respect to the annual climatic cycle. This conclusion was based on results from few studies in a limited number of populations and was subsequently challenged by a long-term seasonal study using time series methods. However, the generality of the seasonal cycles observed was questioned because the data were limited to one population and one chromosome. After resuming and expanding the seasonal study we were able to show that the marked seasonal cycling of D. subobscura inversion polymorphism is not restricted to one chromosome but happens genome-wide at various localities, and the pattern of this cycling neatly matches the seasonal variation in ambient temperature. Though chromosomal inversions are increasingly being recognized as important in adaptive shifts, few studies have examined spatiotemporal patterns in the genetic differentiation of various gene arrangements across and within populations. Why inversion frequencies change (e.g.) seasonally? Why the genetic anomaly for some inversions matched the temperature anomaly during a heat wave? More than half a century after Dobzhansky’s seminal work on inversion polymorphisms inDrosophila we do not yet know the answer to this sort of questions. We believe that the strong seasonal transitions in the chromosomal inversion polymorphism of D. subobscura offer an excellent scenario to tackle these issues. PhD People of the GBBE involved: F. Rodríguez-Trelles, R. Tarrío and M. Santos.


3. Population genomics of Drosophila. The main aim of this research is to describe and explain genome variation (nucleotide and structural) in the model species D. melanogaster. This project takes advantage of the valuable information generated by the Drosophila Genome Reference Panel (DGRP), an initiative for sequencing more than 200 genomes from a natural population of D. melanogaster, in which our group is a participating member. The project tries to answer several interrelated questions, spanning nucleotide and structural variation, epigenetic, expression and developmental data. In addition, we will provide new methods for the detection of selection in the genome. This project represents a significant contribution to the understanding of the very nature of genome variation. We address the following objectives: (i) Search of genomic determinants of protein and nucleotide diversity. Functional annotation coming from modENCODE project will be integrated with population genome data from the DGRP and the Drosophila Population Genomics Project (DPGP); (ii) Development of new estimation methods of detection and measure of natural selection in genome regions undergoing genetic draft; and (iii) Adaptive substitution and conservation in embryonic development genes of Drosophila. Population genomics information will be integrated with our present knowledge on developmental genetics to get a global view of the evolution of embryonic development at the microevolutionary level. PhD People of the GBBE involved: A. Barbadilla, I. Salazar-Ciudad, S. Casillas, R. Egea.


4. Functional and evolutionary study of inversions in the human genome. One of the biggest scientific breakthroughs of the last years is the discovery of a large amount of structural genomic variation in all organisms, including humans. However, despite the long tradition of inversion studies in Drosophila, in humans inversions have been relatively overlooked due to the difficulty of their study. As part of large-scale project funded through an ERC Starting Grant, we have performed a global analysis to determine how many human inversions there really are and have developed high-throughput methods to genotype them in human populations. This information has been stored in the most comprehensive database of human polymorphic inversions, InvFEST (, comprising a few hundred non-redundant inversions. As the next step, we plan to take advantage of all the information generated in the INVFEST project and during many years of study of inversions in Drosophila, to assess the functional and evolutionary impact of inversions in the human genome. We address the following objectives; (i) Determine the functional consequences of inversions in the human genome and their association with phenotypic traits by combining both the experimental genotyping of multiple human polymorphic inversions in hundreds of phenotypically-characterized individuals and the bioinformatic analysis of genome-wide information on gene expression levels, epigenetic modifications and functional annotations; and (ii) The development of new methods for the detection of natural selection in human inversions. Despite decades of study and multiple evidences of the adaptive value of inversions it has been very difficult to determine the targets of selection. PhD People of the GBBE involved: M. Cáceres, A. Barbadilla, M. Puig, S. Casillas, L. Pantano. M. Gayà-Vidal.


5. Mechanisms and evolutionary significance of the difference in basal levels of Hsp70 between warm- and cold-climate O chromosome gene arrangements of D. subobscura. Under intense selection to rapid climate change, trait changes are more likely to be due to genes with large effects. The heat-induced heat-shock proteins Hsp70s have for a long time been considered essential for heat stress survival. The molecular mechanisms of the observed differences in basal levels of Hsp70 between warm- and cold-climate inversions in D. subobscura could range from regulatory changes in coding or non-coding regions, to changes in the size of the gene family between arrangements. We will characterize the Hsp70 gene family at the levels of sequence and genomic organization in both warm-climate and cold-climate gene arrangements on chromosome O, where Hsp70 is located. We will map the members of the gene family on the different arrangements to investigate the connections between chromosomal structural and gene family evolution. We will clone and sequence the region(s) including the members of the Hsp70 family on each arrangement. The information generated will allow us to conduct a comparative analysis between arrangements. In addition, we will obtain data on Hsp70 variation within arrangements that show strong seasonal fluctuations using isogenic lines derived from our samples. PhD People of the GBBE involved: F. Rodríguez-Trelles, Mª P. García Guerreiro, R. Tarrío and M. Santos.


6. Transposable elements (TEs) activity and regulation in original and colonising populations of D. subobscura.TEs are DNA sequences able to be mobilised in host genomes under certain conditions. Original and colonising populations of D. subobscura experience different environmental and demographic regimes, thus constituting a valuable material to study transposition rates and TE regulation. We showed a different TE distribution pattern in original and colonising populations, and also uncovered different germinal and somatic expression rates of TEs gypsy and bilbo among populations and sexes. We do not know whether these differences are correlated to variation in transposition rates, or why TE expression increases in some populations. Recent advances in gene silencing suggest that TEs have silencing mechanisms associated to small interference RNAs whose production depends on genes of the piwi family: Piwi, Aubergine and Argonaute. Our aim is to know the implication of various alleles of the piwi family in the differential patterns of expression observed for bilbo and gypsy, and also to evaluate whether or not our results could be extended to other genome elements. PhD People of the GBBE involved: Mª P. García Guerreiro.


7. TEs in interspecific hybrids of D. buzzatii and D. koepferae: expression and regulation. Hybridisation-induced genomic stress is a causative agent of genomic instability and increase in transposition rates. Working with the sibling species D. buzzatii and D. koepferae we showed a higher transposition rate of the LTR retrotransposon Osvaldo in their hybrids, and also that this increase in transposition rates extends to other TEs as Helena and Galileo. The mechanisms implicated in these results are unknown. Our first aim is to evaluate hybridisation-induced expression rates on the non-LTR TE Helena and compare them with those found for Osvaldo. Second, we will unravel the mechanisms implicated in TEs deregulation in hybrids. Provided that the genomic context could affect epigenetic regulation, we aim to compare the small RNA content of hybrids and parental species. If deregulation in hybrids is due to the lack of specific small RNAS, we would find smaller TE specific RNAs in parental species than in hybrids. PhD People of the GBBE involved: Mª P. García Guerreiro, A. Fontdevila.


8. Study of the genetic networks in embryonic development and their influence in the genotype-phenotype map and in evolution. The study of the relationship between morphological and genetic variation, the genotype-phenotype map, is a major challenge in current evolutionary and developmental biology with implications at all levels of biology and medicine. Our research consists in studying this relationship based on the mathematical modeling of networks of genetic interactions during development. The complex phenotypes of metazoans are formed by the interaction between a large number of genes and the regulation of a limited set of cell behavior (signaling, proliferation, apoptosis, adhesion, etc.). To understand this process we need to study not only the nature of these genes and cell behaviors but also the spatio-temporal dynamics of the networks by which those molecular interactions get coordinated to give rise to macroscopic phenomena/phenotypes. Mathematical modelling offers an unprecedented opportunity to integrate large amounts of experimental evidence on these networks to try to understand their dynamics and their effects on phenotypic variation. Specifically, we study the mechanisms of pattern formation and morphogenesis: how groups of undifferentiated cells give rise to groups of cells with a specific and complex spatial distribution of cell types. The study of these mechanisms is important from an evolutionary standpoint because they determine (together with natural selection) which phenotypic variation is possible and consequently the possible directions of phenotypic change. PhD People of the GBBE involved:  I. Salazar-Ciudad, M. Brun-Usan, M. Marín-Riera.




The Genòmica, Bioinformàtica i Biologia Evolutiva (GBBE) group comprises 15 Ph.D. researchers and 11 predoctoral students and technicians belonging to the UAB Departament de Genètica i de Microbiologia. The common focus of our research is Evolutionary Biology, which provides answers to the complex historical process that accounts for the current Biodiversity on earth. Evolutionary change is the outcome of several population mechanisms (mutation, recombination, natural selection, genetic drift, migration and historical events like colonization of new geographical regions) and can be studied at many different levels. We approach the study of Evolution from a genetic and genomic perspective, althouth we are aware that natural selection operates primarily on the phenotype and thus the relationship genotype-phenotype (development) is crucial to understand adaptation. Genetic variability (nucleotide and chromosomal polymorphisms, gene duplications and new genes, variation in gene expression levels and patterns, etc.) is the raw material of evolution. Therefore, an important issue in evolutionary studies is the characterization and explanation of genetic variation.

Our group seeks to transcend a mere description of diversity patterns and achieve a deep understanding of the mechanisms that generate them. This objective requires several complementary approaches: from experimental and field work, to bioinformatics and modelization. Besides, our experimental work makes use of two different model systems: Drosophila and humans. Our multidisciplinary team includes researches with different but complementary expertise. Good examples of this complementarity are the sequencing project of the Drosophila buzzatii genome led by Alfredo Ruiz that would not have been possible without the bioinformatic assistance of Antonio Barbadilla, or the grant proposal presented recently to the Ministerio de Economia y Competividad by Antonio Barbadilla, Mario Cáceres and Isaac Salazar-Ciudad that includes questions about the interplay between the nucleotide, chromosomal and developmental levels in evolution.

All members of the GBBE pertain currently to the UAB Departament de Genètica i de Microbiologia in Bellaterra (Barcelona). Most of them come from the same origin and have shared many years of common history. Hence, Alfredo Ruiz and Mauro Santos obtained their Ph.Ds. under the mentorship of Antonio Fontdevila, Antonio Barbadilla obtained his Ph.D. under the mentoring of Alfredo Ruiz and Mauro Santos, and Mario Cáceres obtained his Ph.D. under the mentoring of Alfredo Ruiz and Antonio Barbadilla. Shared interests and projects yielded along the years many co-authored papers. As an example we can cite just two: Ruiz, Santos, Barbadilla, Quezada-Díaz, Hasson, Fontdevila (1991 Genetics 128:739-50) and Cáceres, Ranz, Barbadilla, Long, Ruiz (1999, Science 285:415-8). Three researchers later joined this founding group, Isaac Salazar-Ciudad, Francisco Rodriguez-Trelles and Rosa Tarrío. During the last five years (2009-2013), members of GBBE led two research groups recognized and funded by the Direcció General de Recerca de la Generalitat de Catalunya. Our purpose is to join forces to take advantage of the synergies generated by the diversity and complementarity of our approaches. We consider this merging as the culmination of a long shared history of interest in evolutionary biology.