Evolution of the synapse transcriptome

Izquierdo Barraza, Abril (2019) Evolution of the synapse transcriptome. PhD thesis, University of Nottingham.

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Abstract

The vast cognitive repertoire seen within the animal kingdom from rudimentary forms of habituation and information-processing to highly complex cognitive processes that confers the ability to adapt to challenging environments is a topic of great interest. The presynaptic and postsynaptic terminals of the synapse form an immensely structured protein network, the origin of which has been proposed to precede the origin of multicellularity in elementary cell signalling pathways. Such molecules were central for the arrangement of macromolecular complexes through genome duplications and posterior diversification in the vertebrate evolution. Yet, mutations in the postsynaptic density (PSD) are associated to more than 130 neurological alterations. It is therefore fundamental to better understand brain gene expression and evolution of these genes. Proteomic analysis of the synapse have characterised more than 1,500 proteins, however strikingly, there is a lack of research using recent transcriptomics approaches.

This PhD thesis contributes to understanding of comparative synaptic biology by exploiting NGS technologies to generate a comprehensive analysis of gene expression of brain tissues. A de novo transcriptome assembly pipeline was developed and employed to that end. We sequenced and generated a de novo transcriptome from brain tissues of zebrafish, bat and lion to explore the presence of genes known to be essential in learning and memory (Emes and Grant, 2012). To adequately provide a richer understanding of neurological diseases in humans, it is essential to investigate the magnitude of which metazoan genes shared orthologs. Transcripts enriched and specific to each tissue were determined, along with the analysis of which mouse orthologous genes were present in the brain, synaptosome (SYN) and PSD of zebrafish, bat and lion.

This research revealed a strong conservation of PSD and SYN components, where the genes with the highest expression in the three species, i.e., cell-adhesion and signalling enzymes represent the core adaptive machinery of the ancestral synapse. In addition, this work demonstrates a substantial connection of highly expressed genes with critical neurodegenerative diseases, highlighting the urgency to improve the understanding of synaptic dysfunction. Lastly, this study provides the first exploration of bat and lion transcripts encoded in the brain, SYN and PSD, in which species-specific adaptations were found, along with evidence of convergent evolution in the echolocating bat.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Emes, Richard
Chakrabarti, Lisa
Keywords: Comparative synaptic biology; Gene expression; Brain tissues; Metazoan genes; Orthologous genes
Subjects: Q Science > QP Physiology > QP351 Neurophysiology and neuropsychology
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Veterinary Medicine and Science
Item ID: 56826
Depositing User: Izquierdo Barraza, Abril
Date Deposited: 11 Sep 2019 08:09
Last Modified: 06 May 2020 15:16
URI: http://eprints.nottingham.ac.uk/id/eprint/56826

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