Assembly and evolution of tissue-specific exon networks

Assembly and evolution of tissue-specific exon networks

Lab members: Demián Burguera, Yamile Márquez, Antonio Torres-Méndez
Funding: MINECO, 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? Using alternative exons and their master regulators as case examples, in this research line we are trying to answer these questions by reconstructing the stepwise assembly of various tissue-specific splicing networks.

 

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.

 

 

Key questions to investigate evolutionary conservation of a splicing regulatory network. We need to evaluate conservation at multiple levels: a) conservation of the orthologs that would harbor the exons; b) genomic conservation of the exons; c) whether the exons are alternatively spliced in other species; and d) whether those exons are also regulated by the same master alternative splicing factor.

 

Related publications:

  • 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.