Uncovering the role of taxonomically restricted genes in the basal metazoan Hydra

• Applicant: Privatdozent Dr. Alexander Klimovich, Ph.D.
• Subject Area: Evolutionary Cell and Developmental Biology (Zoology)
• Term: from 2021 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 468104244

Up to 40% of genes in the genome of every animal species are represented by non-conserved, taxonomically restricted genes (TRGs). These genes show no homology to other genes outside this species or clade and therefore are restricted to a species, genus or phylum. Despite advances in understanding the mechanisms of TRGs emergence, the functional role TRGs remains a major puzzle in developmental biology. Due to difficulties in TRG identification and annotation by homology-based approaches, no studies have attempted to systematically characterize the repertoire of TRGs in a certain species. Hence, it remains poorly understood, what cellular role do TRGs play, how do they complement the highly conserved molecular toolkit of Metazoa, and how do lineage-specific genes contribute to development, gene-environment interactions and clade-specific adaptations. To uncover the developmental role of TRGs, I propose to use an evolutionary informative, experimentally and genetically accessible model - the freshwater polyp Hydra. Our preliminary observations point to a remarkably high abundance of TRGs in Hydra genome and provide evidence for a complex cell type-specific and context-dependent expression of TRGs. Our findings suggest that the proteins encoded by TRGs in Hydra are structurally diverse and subject to selective pressure. They may be implicated in such processes as stem-cell maintenance and cell type diversification, interlineage communication and neurotransmission, gene-environment interactions and metaorganism homeostasis. I propose to perform a genome-wide examination of structural and functional diversity of proteins encoded in TRGs in H. vulagris AEP. Specifically, I will address the role of TRG-encoded proteins in conferring cell type identity, and particularly – in the individualization of neuronal types. To address this goal, I intend, firstly, to improve the assembly and annotation of H. vulgaris AEP genome. Further, I will identify and classify all proteins encoded by TRGs in Hydra genome, reveal the principles of their expression, and infer their structure and function. My study promises first insights into the role of genomic novelty in diversification of metazoan cell types, particularly – the neurons. It may stimulate revising the conventional view on evolution of cell types, where highly conserved genes are assumed to play a leading role. In a long-term perspective, my study may provide both conceptual and methodological framework for studying the role of the ubiquitous TRGs in diverse model systems. The first high-quality genome of the strategically important H. vulgaris AEP strain will become a useful resource for the community and myself. My systematic analysis of the TRGs diversity in Hydra, of their genomic context and expression patterns will provide a basis for understanding the regulation of TRGs. It will provide a ground for further hypothesis-driven functional analysis of individual TRGs and their families using transgenesis.

• DFG Programme: Research Grants