Dataset Information

Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA.

ABSTRACT: MoeA, or gephyrin in higher eukaryotes, is crucial for molybdenum cofactor biosynthesis required in redox reactions. Gephyrin is a moonlighting protein also involved in postsynaptic receptor clustering, a feature thought to be a recent evolutionary trait. We showed previously that a repurposed copy of MoeA (Glp) is involved in bacterial cell division. To investigate how MoeA acquired multifunctionality, we used phylogenetic inference and protein structure analyses to understand the diversity and evolutionary history of MoeA. Glp-expressing Bacteria have at least two copies of the gene, and our analysis suggests that Glp has lost its enzymatic role. In Archaea we identified an ancestral duplication where one of the paralogs might bind tungsten instead of molybdenum. In eukaryotes, the acquisition of the moonlighting activity of gephyrin comprised three major events: first, MoeA was obtained from Bacteria by early eukaryotes, second, MogA was fused to the N-terminus of MoeA in the ancestor of opisthokonts, and finally, it acquired the function of anchoring GlyR receptors in neurons. Our results support the functional versatility and adaptive nature of the MoeA scaffold, which has been repurposed independently both in eukaryotes and bacteria to carry out analogous functions in network organization at the cell membrane.

SUBMITTER: Megrian D

PROVIDER: S-EPMC11291035 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA.

Megrian Daniela D Martinez Mariano M Alzari Pedro M PM Wehenkel Anne Marie AM

bioRxiv : the preprint server for biology 20240723

MoeA, or gephyrin in higher eukaryotes, is crucial for molybdenum cofactor biosynthesis required in redox reactions. Gephyrin is a moonlighting protein also involved in postsynaptic receptor clustering, a feature thought to be a recent evolutionary trait. We showed previously that a repurposed copy of MoeA (Glp) is involved in bacterial cell division. To investigate how MoeA acquired multifunctionality, we used phylogenetic inference and protein structure analyses to understand the diversity and ...[more]

PMID: 39091723

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Project description:One common research goal in systems neurosciences is to understand how the functional relationship between a pair of regions of interest (ROIs) evolves over time. Examining neural connectivity in this way is well-suited for the study of developmental processes, learning, and even in recovery or treatment designs in response to injury. For most fMRI based studies, the strength of the functional relationship between two ROIs is defined as the correlation between the average signal representing each region. The drawback to this approach is that much information is lost due to averaging heterogeneous voxels, and therefore, the functional relationship between a ROI-pair that evolve at a spatial scale much finer than the ROIs remain undetected. To address this shortcoming, we introduce a novel evolutionary computation (EC) based voxel-level procedure to examine functional plasticity between an investigator defined ROI-pair by simultaneously using subject-specific BOLD-fMRI data collected from two sessions seperated by finite duration of time. This data-driven procedure detects a sub-region composed of spatially connected voxels from each ROI (a so-called sub-regional-pair) such that the pair shows a significant gain/loss of functional relationship strength across the two time points. The procedure is recursive and iteratively finds all statistically significant sub-regional-pairs within the ROIs. Using this approach, we examine functional plasticity between the default mode network (DMN) and the executive control network (ECN) during recovery from traumatic brain injury (TBI); the study includes 14 TBI and 12 healthy control subjects. We demonstrate that the EC based procedure is able to detect functional plasticity where a traditional averaging based approach fails. The subject-specific plasticity estimates obtained using the EC-procedure are highly consistent across multiple runs. Group-level analyses using these plasticity estimates showed an increase in the strength of functional relationship between DMN and ECN for TBI subjects, which is consistent with prior findings in the TBI-literature. The EC-approach also allowed us to separate sub-regional-pairs contributing to positive and negative plasticity; the detected sub-regional-pairs significantly overlap across runs thus highlighting the reliability of the EC-approach. These sub-regional-pairs may be useful in performing nuanced analyses of brain-behavior relationships during recovery from TBI.

Dataset Information

Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA.

Publications

Evolutionary plasticity and functional repurposing of the essential metabolic enzyme MoeA.

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