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Propensity for proto-gene emergence in bacteria

ABSTRACT: The birth of new genes from non-coding sequences has been postulated to be preceded by a proto-gene phase, in which a sequence is translated into protein but does not exhibit hallmarks of a clear function. Despite the abundance of such proto-genes in bacterial genomes, the frequency of their emergence and whether they actually act as precursors of new genes in natural populations are still open questions. To address these issues, we applied a combination of transcriptomic, proteomic and comparative genomic approaches to identify and analyze hundreds of novel bacterial protein-coding genes that have previously escaped annotation. These novel proteins, including many that are widely conserved across genera, display sequence properties indistinguishable from the non-coding regions of the genome, suggesting that the vast majority are evolving neutrally. We provide evidence of de novo emergence of three proto-genes within the history of the E. coli species; however, most such elements are formed via the mutational modification of existing open reading frames. Contrary to expectations, we discover that proto-genes emerge at a uniform rate across distant bacterial taxa despite significant differences in their genomic characteristics, suggesting the presence of taxon-specific mechanisms that regulate their origination and persistence.

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ORGANISM(S): Escherichia Coli Bacteria

SUBMITTER: Md Hassan uz-Zaman

LAB HEAD: Howardh Ochman

PROVIDER: PXD062120 | Pride | 2025-09-19

REPOSITORIES: Pride

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Project description:Spider venoms are a unique source of bioactive peptides displaying remarkable structural stability and potent neuroactivity. Phoneutria nigriventer, often referred to as Brazilian wandering spider, banana spider or “armed” spider, is endemic from South America and amongst the most dangerous venomous spiders in the world. Envenomation accidents with P. nigriventer often occur in Brazil with approximately 4,000 cases per year and which symptoms include priapism, hypertension, blurred vision, sweating, and vomiting, amongst others. Besides its clinical relevance, P. nigriventer venom comprises promising peptide drug leads providing therapeutic effects in a range of disease models. In this study, we further explored the neuroactivity and molecular diversity of the venom from P. nigriventer using fractionation-guided high-throughput cellular assays coupled to proteomics analysis and multi-pharmacology activity to broaden the knowledge and therapeutic potential of this venom, as well as a proof-of-concept for an investigative pipeline to study spider-venom derived neuroactive peptides. We applied ion channel assays in a neuroblastoma cell line to investigate modulation of voltage-gated sodium and calcium channels, and nicotinic acetylcholine α7 receptor. We then investigated the venom components using mass spectrometry to identify peptide masses and sequences associated to the observed neuromodulations. Our findings showed this venom is highly complex compared to other neurotoxin-rich venoms and comprises potent modulators of voltage-gated sodium and calcium channels which were classified into 4 families of neuroactive peptides based on their activities and structures. In addition to the reported P. nigriventer neuroactive peptides, we identified at least 27 novel cysteine-rich venom peptides in which neuroactivities are still to be elucidated in voltage-gated ion channels and other potential targets. Our findings provide a new basis for studying non-explored bioactivities of known and novel neuroactive components in P. nigriventer venom, and further supports the successful application of our discovery pipeline for identifying ion channel-targeting venom peptides with potential to become drug leads with diverse exploratory and therapeutic applications.

			Action	DRS
	8925_HUZ_01.mgf	Mgf
	8925_HUZ_01.mzid	Mzid
	8925_HUZ_01.raw	Raw
	8925_HUZ_02.mgf	Mgf
	8925_HUZ_02.mzid	Mzid

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Propensity for proto-gene emergence in bacteria

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