Our main research focuses on how to use molecular pathways to understand the biology of adaptation through the measures of natural selection in genes and other genomic regions. The different forms of selection (purifying, balancing and positive) are analyzed at two levels: among human populations in order to detect population-specific adaptations, and among primates in order both to recognize species-specific adaptive selection and to measure the relative strength of purifying selection. We have also ongoing work in understanding recombination and in reconstructing population history by studying human genetic diversity. We are also collaborating with Carles Lalueza-Fox in ancient DNA studies and with Elena Bosch in detecting positive selection.
The action of natural selection is at the base of different amounts of genetic dispensability or relative importance (in cases of negative or purifying selection) or of adaptation (in cases of positive selection and in the special case of balancing selection) that will be population-specific (in the case of human diversity) or species-specific (in the case of genetic divergence). The action of selection is measured and understood not in terms of single lists of genes, but integrated in molecular physiological pathways or networks and the aim is, in a given pathway, to understand the complex basis of adaptation and how networks have been shaped by natural selection. The final goal is, on one hand, to understand in specific pathways how evolution has taken place, where positive selection (and balancing selection) has taken place and where purifying selection has been shaping the genome, and on the other, to obtain possible general patterns of evolution in molecular pathways and networks.
Data is retrieved mostly from pre-existing databases but, in cases of doubt, low quality or low density, we produce our own (sequences and SNPs). Inter-specific data include the sequences of several primates and intra-specific databases include: HapMap, in versions 2 and 3; SNP analysis of the HGDP panel with the 650k array of Illumina; and Re-sequencing projects (like Seattle-SNP) 1000 genomes. The pathways that we are analyzing are: N-glycans; integration of all glycosylation pathways; innate immunity; skin pigmentation; visual perception and obesity through adiposity signals.
Taking also a pathway approach we are studying the genetic susceptibility to placental malaria in a case-control setting in a population in Manhiça, Mozambique. This project is in collaboration with Pedro Alonso and other members of the Barcelona Center for International Health Research (CRESIB). High throughput genotyping data has been generated and the analysis has been centered mostly in innate immunity and glycosylation.
Recombination is a main force shaping genome diversity. In collaboration with Laxmi Parida (Computational Biology Center, IBM T J Watson Research, Yorktown, USA), we have developed an algorithm, implemented in the IRiS program, to detect past recombination events in extant sequences, with specificity of parental and recombinant sequences. The algorithm detects recombination events from tree incompatibilities found along the sequence. We have validated and calibrated the algorithm for the human genome given human demographic history and the human recombination model by means of coalescent simulations implementing a standard model of human demography. In this project is also involved Francesc Calafell; We are also interested in the evolution of recombination and differences in rates among human populations and have demonstrated that there is stratification in the recombination rates among human populations strongly related to genetic distances. In collaboration with Elena Bosch we have shown that most isolated populations do not show a special pattern of linkage disequilibrium.
In collaboration with David Comas we are participating in the Genographic Project promoted by National Geographic and IBM as responsible for Central and Western Europe and participating in a variety of population specific studies (including Basques, North African, South Saharian and others).
Parnell LD, Lindenbaum P, Shameer K, Dall'Olio GM, Swan DC, et al. 2011 BioStar: An Online Question & Answer Resource for the Bioinformatics Community. PLoS Comput Biol 7(10): e1002216. doi:10.1371/journal.pcbi.1002216
Casals F, Sikora M, Laayouni H, Montanucci L, Muntasell A, Lazarus R, Calafell F, Awadalla P, Netea MG, Bertranpetit J. Genetic adaptation of the antibacterial human innate immunity network. BMC Evol Biol. 2011 Jul 11;11(1):202. Ahead of print.
AS PART OF THE GENOGRAPHIC CONSORTIUM:
Bosch, E., Laayouni, H., Morcillo-Suárez, C., Casals, F., Moreno-Estrada, A., Ferrer-Admetlla, A., Gardner, M., Rosa, A., Navarro, A., Comas, D., Graffelman, J., Calafell, F., Bertranpetit, J. 2009. Decay of linkage disequilibrium within genes across HGDP-CEPH human samples: most population isolates do not show increased LD. BMC Genomics 10:338.
Casals, F., Ferrer-Admetlla, A., Sikora, M., Ramírez-Soriano, A., Marquès-Bonet, T., Despiau, S., Roubinet, F., Calafell, F., Bertranpetit, J., Blancher, A. 2009. Human pseudogenes of the ABO family show a complex evolutionary dynamics and loss of function. Glycobiology Jun. 19: 6:583-91. Epub Feb. 13. PMID: 19218399.
Ferrer-Admetlla, A., Sikora, M., Laayouni, H., Esteve, A., Roubinet, F., Blancher, A., Calafell, F., Bertranpetit, J., Casals, F. 2009. A natural history of FUT2 polymorphism in humans. Molecular Biology and Evolution 26:1993-2003.
Garagnani, P., Laayouni, H., González-Neira, A., Sikora, M., Luiselli, D., Bertranpetit, J., Calafell, F. 2009. Isolated populations as treasure troves in genetic epidemiology: the case of the Basques. European Journal of Human Genetics (EJHG) 17: 1490-1494.
Helgason, A., Lalueza-Fox, C., Ghosh, S., Sigurethardóttir, S., Sampietro, M.L., Gigli, E., Baker, A., et al. 2009. Sequences from first settlers reveal rapid evolution in Icelandic mtDNA pool. PLoS Genetics 5 (1), 1 e1000343.
Moreno-Estrada, A., Tang, K., Sikora, M., Marquès-Bonet, T., Casals, F., Navarro, A., Calafell, F., Bertranpetit, J., Stoneking, M., Bosch, E. 2009. Interrogating 11 fast-evolving genes for signatures of recent positive selection in worldwide human populations. Molecular Biology and Evolution 26: 2285-2297.
Laayouni, H., Bertranpetit, J. 2009. From the detection of population structure to the reconstruction of population history: the historical reading of the human genome. Heredity 103: 362-363.
Lu, T.T., Lao, O., Nothnagel, M., Junge, O., Freitag-Wolf, S., Caliebe, A., Balascakova, M. et al. 2009. An evaluation of the genetic-matched pair study design using genome-wide SNP data from the European population. European Journal of Human Genetics (EJHG) 17: 967-975.
Parida, L., Javed, A., Melé, M., Calafell, F., Bertranpetit, J. 2009. Minimizing recombi-nations in consensus networks for phylogeographic studies. BMC Bioinformatics 10 Suppl 1: S72.
Ramírez, O., Gigli, E., Bover, P., Alcover, J.A., Bertranpetit, J., Castresana, J., Lalueza-Fox, C. 2009. Paleogenomics in a temperate environment: Shotgun sequencing from an extinct Mediterranean caprine. PLoS ONE 4, e5670.
Sikora, M., Ferrer-Admetlla, A., Laayouni, H., Menéndez, C., Mayor, A., Bardaji, A., Sigauque, B., et al. 2009. A variant in the gene FUT9 is associated with susceptibility to placental malaria infection. Human Molecular Genetics 18: 3136-3144.
Project Title: Factores de riesgo genético en la Malaria
Financed by: Ministerio de Educación y Ciencia (MEC-SAF2007-63171)
PI: Jaume Bertranpetit
Project Title: Grup de Recerca Consolidat-SGR
Financed by: Generalitat de Catalunya (2009 SGR-1101)
PI: Jaume Bertranpetit
Project Title: The Genographic project: Western/Central Europe region
Financed by: National Geographic and IBM
PIs: Jaume Bertranpetit and David Comas