@article {125200, title = {The layered costs and benefits of translational redundancy.}, journal = {Elife}, volume = {12}, year = {2023}, month = {2023 Mar 02}, abstract = {

The rate and accuracy of translation hinges upon multiple components - including transfer RNA (tRNA) pools, tRNA modifying enzymes, and rRNA molecules - many of which are redundant in terms of gene copy number or function. It has been hypothesized that the redundancy evolves under selection, driven by its impacts on growth rate. However, we lack empirical measurements of the fitness costs and benefits of redundancy, and we have poor a understanding of how this redundancy is organized across components. We manipulated redundancy in multiple translation components of by deleting 28 tRNA genes, 3 tRNA modifying systems, and 4 rRNA operons in various combinations. We find that redundancy in tRNA pools is beneficial when nutrients are plentiful and costly under nutrient limitation. This nutrient-dependent cost of redundant tRNA genes stems from upper limits to translation capacity and growth rate, and therefore varies as a function of the maximum growth rate attainable in a given nutrient niche. The loss of redundancy in rRNA genes and tRNA modifying enzymes had similar nutrient-dependent fitness consequences. Importantly, these effects are also contingent upon interactions across translation components, indicating a layered hierarchy from copy number of tRNA and rRNA genes to their expression and downstream processing. Overall, our results indicate both positive and negative selection on redundancy in translation components, depending on a species{\textquoteright} evolutionary history with feasts and famines.

}, keywords = {Biological Evolution, Cost-Benefit Analysis, Escherichia coli, Exercise, Gene Dosage}, issn = {2050-084X}, doi = {10.7554/eLife.81005}, author = {Raval, Parth K and Ngan, Wing Yui and Gallie, Jenna and Agashe, Deepa} } @article {880, title = {Gene dosage in the dysbindin schizophrenia susceptibility network differentially affect synaptic function and plasticity.}, journal = {J Neurosci}, volume = {35}, year = {2015}, month = {2015 Jan 7}, pages = {325-38}, abstract = {

Neurodevelopmental disorders arise from single or multiple gene defects. However, the way multiple loci interact to modify phenotypic outcomes remains poorly understood. Here, we studied phenotypes associated with mutations in the schizophrenia susceptibility gene dysbindin (dysb), in isolation or in combination with null alleles in the dysb network component Blos1. In humans, the Blos1 ortholog Bloc1s1 encodes a polypeptide that assembles, with dysbindin, into the octameric BLOC-1 complex. We biochemically confirmed BLOC-1 presence in Drosophila neurons, and measured synaptic output and complex adaptive behavior in response to BLOC-1 perturbation. Homozygous loss-of-function alleles of dysb, Blos1, or compound heterozygotes of these alleles impaired neurotransmitter release, synapse morphology, and homeostatic plasticity at the larval neuromuscular junction, and impaired olfactory habituation. This multiparameter assessment indicated that phenotypes were differentially sensitive to genetic dosages of loss-of-function BLOC-1 alleles. Our findings suggest that modification of a second genetic locus in a defined neurodevelopmental regulatory network does not follow a strict additive genetic inheritance, but rather, precise stoichiometry within the network determines phenotypic outcomes.

}, keywords = {Animals, Animals, Genetically Modified, Carrier Proteins, Drosophila, Drosophila Proteins, Dystrophin-Associated Proteins, Female, Gene Dosage, Nerve Net, Neuronal Plasticity, Schizophrenia, Synapses, Synaptic Transmission}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.3542-14.2015}, author = {Mullin, Ariana P and Sadanandappa, Madhumala K and Ma, Wenpei and Dickman, Dion K and VijayRaghavan, Krishnaswamy and Ramaswami, Mani and Sanyal, Subhabrata and Faundez, Victor} } @article {127108, title = {Diversity, expression and mRNA targeting abilities of Argonaute-targeting miRNAs among selected vascular plants.}, journal = {BMC Genomics}, volume = {15}, year = {2014}, month = {2014 Dec 02}, pages = {1049}, abstract = {

BACKGROUND: Micro (mi)RNAs are important regulators of plant development. Across plant lineages, Dicer-like 1 (DCL1) proteins process long ds-like structures to produce micro (mi) RNA duplexes in a stepwise manner. These miRNAs are incorporated into Argonaute (AGO) proteins and influence expression of RNAs that have sequence complementarity with miRNAs. Expression levels of AGOs are greatly regulated by plants in order to minimize unwarranted perturbations using miRNAs to target mRNAs coding for AGOs. AGOs may also have high promoter specificity-sometimes expression of AGO can be limited to just a few cells in a plant. Viral pathogens utilize various means to counter antiviral roles of AGOs including hijacking the host encoded miRNAs to target AGOs. Two host encoded miRNAs namely miR168 and miR403 that target AGOs have been described in the model plant Arabidopsis and such a mechanism is thought to be well conserved across plants because AGO sequences are well conserved.

RESULTS: We show that the interaction between AGO mRNAs and miRNAs is species-specific due to the diversity in sequences of two miRNAs that target AGOs, sequence diversity among corresponding target regions in AGO mRNAs and variable expression levels of these miRNAs among vascular plants. We used miRNA sequences from 68 plant species representing 31 plant families for this analysis. Sequences of miR168 and miR403 are not conserved among plant lineages, but surprisingly they differ drastically in their sequence diversity and expression levels even among closely related plants. Variation in miR168 expression among plants correlates well with secondary structures/length of loop sequences of their precursors.

CONCLUSIONS: Our data indicates a complex AGO targeting interaction among plant lineages due to miRNA sequence diversity and sequences of miRNA targeting regions among AGO mRNAs, thus leading to the assumption that the perturbations by viruses that use host miRNAs to target antiviral AGOs can only be species-specific. We also show that rapid evolution and likely loss of expression of miR168 isoforms in tobacco is related to the insertion of MITE-like transposons between miRNA and miRNA* sequences, a possible mechanism showing how miRNAs are lost in few plant lineages even though other close relatives have abundantly expressing miRNAs.

}, keywords = {Argonaute Proteins, Base Sequence, Binding Sites, Disease Resistance, Gene Dosage, Gene Expression Regulation, Plant, Genetic Variation, Genotype, Host-Pathogen Interactions, MicroRNAs, Molecular Sequence Data, Nucleic Acid Conformation, Plants, RNA Precursors, RNA, Messenger, RNA, Plant, Sequence Alignment, Species Specificity}, issn = {1471-2164}, doi = {10.1186/1471-2164-15-1049}, author = {Jagtap, Soham and Shivaprasad, Padubidri V} }