Functional genomics, microsynteny and the origin of vertebrates

Functional genomics, microsynteny and the origin of vertebrates

Lab members: Demián Burguera, Laura Lopez-Blanch, Chris Wyatt, Maria Touceda-Suárez, Yamile Marquez.
Funding: CRG.

One of our main interests is to understand how vertebrates originate. This is a simple question that nonetheless has a remarkably complex set of answers that must cover from changes in genome function and organization to the evolution of the unique vertebrate brain. We currently take several complementary approaches including:

(i) Comparative functional genomics: as part of a large collaborative effort with many labs integrating the European Amphioxus Genome Consortium, we co-led the sequencing, assembly and functional annotation of the European amphioxus, Branchiostoma lanceolatum. In this consortium, we generated multiple functional genomics data for this non-vertebrate chordate (including transcriptomic, ATAC-seq, 5mC-seq, CAGE-seq and ChIP-seq), to discover conserved and novel functional features of vertebrate genomes. Our lab keeps generating new data and resources for this key species to try to understand how vertebrates have originated.

(ii) Evolution of microsynteny after whole genome duplication: The order of genes along metazoan chromosomes has generally been thought to be largely random, with few implications for organismal function. However, though a multi-species genome comparison, we found hundreds of pairs of genes that have remained linked in diverse metazoan species over hundreds of millions of years of evolution, suggesting widespread cis-regulatory constains for gene order. Among them, the most interesting from an Evo-Devo perspective are Genomic Regulatory Blocks (GRBs): blocks of conserved microsynteny involving a developmental gene whose cis-regulatory elements spread across neighboring bystander genes. In this research line, we are interested in understanding how ancient GRBs have evolved after the whole genome duplications of vertebrates. Differential gene conservation and loss after these duplications have contributed to shape our genomes, providing explanations for striking features such as ancient vast gene deserts.

Modified from Irimia et al, Trend Genet 2013

(iii) Evolutionary origin of the vertebrate brain: According to textbooks, vertebrate brains develop from a neural tube that rapidly becomes regionalized into the forebrain (which includes the secondary prosencephalon and diencephalon), midbrain, and hindbrain. These regions are then further subdivided; in particular, the diencephalon gives rise to the prethalamus, thalamus, and pretectum. However, classic embryological manipulations of brain signaling centers showed that the prethalamus behaves very differently than the thalamus and pretectum, which largely share their developmental potential with the midbrain. Therefore, this textbook partition scheme might not be fully consistent from a developmental perspective. To shed new light on this question and to better understand the origin and evolution of the vertebrate brain, we built a comprehensive molecular model of the regionalization of the incipient neural tube of amphioxus, a non-vertebrate chordate that shares multiple features with its vertebrate relatives. This model shows that the amphioxus nervous system shares its basic blueprint with that of vertebrates. However, a single undivided region in amphioxus, which we termed Di-Mesencephalic primordium (DiMes), unambiguously corresponds to the region encompassing the thalamus, pretectum, and midbrain in vertebrates, indicating that these regions are also more closely related evolutionarily. Therefore, the diencephalon as a neuroanatomical compartment as well as the classic separation between forebrain and midbrain in vertebrates appear inconsistent from both an evolutionary and developmental perspective. We are now using single-cell RNA-seq techniques and comparative transcriptomics to gain further insight into the origin of the vertebrate brain.

Related publications:

  • Touceda-Suárez, M., Kita, E.M., Acemel, R.D., Firbas, P.N., Magri, M.S., Naranjo, S., Tena, J.J., Gómez-Skarmeta, J.L.†, Maeso, I.†, Irimia, M.† (2019). Ancient genomic regulatory blocks are a major source for gene deserts in vertebrates after whole genome duplications. bioRxiv, https://doi.org/10.1101/776369.
  • 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.
  • Albuixech-Crespo, B., Lopez-Blanch, L., Burguera, D., Maeso, I., Sánchez Arrones, L., Moreno-Bravo, J.A., Somorjai, I., Pascual-Anaya, J., Puelles, E., Bovolenta, P., Garcia-Fernàndez, J.†, Puelles, L.†, Irimia, M.†, Ferran, J.L.† (2017). Molecular regionalization of the developing amphioxus neural tube challenges major partitions of the vertebrate brain. PLoS Biol, 15:e2001573.
  • Irimia, M., Maeso, I., Tena, J.J., Roy, S.W., Fraser, H.B. (2013). Ancient cis-regulatory constraints and the evolution of genome architecture. Trends Genet, 29(9):521-8.
  • Irimia, M., Tena, J.J., Alexis, M.S., Fernandez-Miñan, A., Maeso, I., Bogdanović, O., de la Calle-Mustienes, E., Roy, S.W., Gomez-Skarmeta, J.L., Fraser, H.B. (2012). Extensive Conservation of Ancient Microsynteny across Metazoans due to cis-regulatory Constraints. Genome Res, 22(12): 22(12):2356-67.