Assembly and evolution of tissue-specific transcriptomic networks
Lab members: Yamile Márquez, Antonio Torres-Méndez, Fede Mantica, Reza Sodaei.
Funding: ERC Starting Grant, Plan Estatal, EMBO, CRG
Novel organismal structures in metazoans are often undergirded by complex cell type- or tissue-specific gene regulatory networks. As such, understanding the emergence of new structures through evolution requires reconstructing the series of evolutionary steps leading to these underlying networks. However, the basic elements that form these networks are often so functionally interdependent that understanding their step-by-step emergence during evolution imposes multiple dilemmas: Did the gene network pre-exist the organismal structure? Did the targets pre-exist the tissue-specific regulators? Did the regulators ancestrally have tissue-specific expression or did they acquire it in certain lineages? Are the downstream targets conserved in the case of regulators with well-conserved expression across species?
In this research line, we try to reconstruct the stepwise assembly of various tissue-specific gene and splicing networks. For this purpose, we perform comparative genomic and transcriptomic analyses of multiple homologous tissues across many bilaterian animals. We also focus on specific exon networks regulated by key splicing factors (e.g. Srrm3/4, Nova, Esrp, etc).
Schematic representation of a cell type-specific gene regulatory module for Cell Type B. Upon activation of a master regulator of Cell Type B, several target genes are activated (genes 1 and 2) or silenced (gene 5), which will generate the transcriptome identity of Cell Type B. Comprehending how such modules originate in evolution requires understanding how the master regulator, its cell type-specific expression and its targets and regulatory motifs all co-evolved together.
- Torres-Méndez, A., Bonnal, S., Marquez, Y., Roth, J., Iglesias, M., Permanyer, J., Almudí, I., O’Hanlon, D., Guitart, T., Soller, M., Gingras, A.-C., Gebauer, F., Rentzsch, F., Blencowe, B.J.B., Valcárcel, J., Irimia, M.† (2019). A novel protein domain in an ancestral splicing factor drove the evolution of neural microexons. Nature Ecol Evol, 3:691-701
- Irimia, M.†, Maeso, I. (2019). Boosting macroevolution: genomic changes triggering qualitative expansions of regulatory potential. On: Old questions and young approaches to animal evolution. Springer-Nature.
- Marletaz, F., Firbas, P., Maeso, I., Tena, J.J., Bogdanovic, O., Perry, M., Wyatt, C.D.R., [+50 authors including Marquez, Y., Burguera, D. and Permanyer, J.], Holland, P.W.H., Escriva, H.†, Gomez-Skarmeta, J.L.†, Irimia, M.† (2018). Amphioxus functional genomics and the origins of vertebrate gene regulation. Nature, 564:64-70
- Grau-Bove, X., Ruiz-Trillo, I.†, Irimia, M.† (2018). Origin of exon skipping-rich transcriptomes in animals driven by evolution of gene architecture. Genome Biol, 19:135.
- Burguera, D., Marquez, Y., Racioppi, C., Permanyer, J., Torres-Mendez, T., Esposito, R., Albuixech, B., Fanlo, L., D'Agostino, Y., Gohr, A., Navas-Perez, E., Riesgo, A., Cuomo, C., Benvenuto, G., Christiaen, L.A., Martí, E., D'Aniello, S., Spagnuolo, A., Ristoratore, F., Arnone, M.I.†, Garcia-Fernàndez, J.†, Irimia, M.† (2017). Evolutionary recruitment of flexible Esrp-dependent splicing programs into diverse embryonic morphogenetic processes. Nat Commun, 8:1799.
- Solana, J.*†, Irimia, M.*†, Ayoub, S., Orejuela, M.R., Zywitza, V., Jens, M., Tapial, J., Ray, D., Morris, Q.D., Hughes, T.R., Blencowe, B.J., Rajewsky, N.† (2016). Conserved functional antagonism between CELF and MBNL proteins regulates stem cell-specific alternative splicing and regeneration in planarians. Elife, 5:e16797.
- Irimia, M., Denuc, A., Burguera, D., Somorjai, I., Martin-Duran, J.M., Genikhovich, G., Jimenez-Delgado, S., Technau, U., Roy, S.W., Marfany, G., Garcia-Fernandez, J. (2011). Stepwise Assembly of the Nova-regulated Alternative Splicing Network in the Vertebrate Brain. Proc Natl Acad Sci USA, 108(13):5319-24.