Biology subjects

Riadi, G.

Publications and source records attributed to Riadi, G..

7 recordsLinked to original sources

bioRxiv2026

Evolution of ion channels in the water-to-land transition of vertebrates

The transition of vertebrates from aquatic to terrestrial environments represents one of the most profound evolutionary events in their history, involving extensive physiological and morphological innovations. Key adaptations included the transformation of fins into limbs with digits to enable efficient terrestrial locomotion, the ability to perceive novel environmental stimuli, and the emergence of reproductive strategies suited to life on land, processes in which ion channels played fundamental roles. Accordingly, understanding the genetic basis of vertebrate terrestrialization requires investigating the evolution of this group of membrane proteins. Our analyses reveal that the proportion of ion channel genes is highly conserved, representing approximately 1.4% to 1.6% of total protein-coding genes in most lineages, with a notable increase to [~]1.9% in teleost fishes. Our natural selection analyses revealed an overrepresentation of specific ion channel gene families, including TRP, RyR, HTR3, and HCN. We identified 29 ion channel genes showing signatures of positive selection, many of which are associated with key physiological functions such as nociception and thermosensation. We also detected an elevated rate of gene turnover in the common ancestor of terrestrial vertebrates, indicative of substantial genomic remodeling through gene gain and loss. Together, these findings suggest that, despite overall conservation in the proportions of ion channel genes, specific gene families underwent changes that were likely critical to meeting the physiological demands of terrestrial life. These results provide a foundation for future comparative and functional studies aimed at elucidating the molecular mechanisms underlying major environmental transitions. SignificanceThe transition from water to land was one of the most important events in vertebrate evolution, requiring animals to detect new environmental cues, sense temperature, coordinate movement, and cope with unfamiliar pathogens and physical stresses. Because ion channels control many of these physiological processes, they provide an ideal system for investigating the molecular basis of vertebrate terrestrialization. By tracing their evolutionary history across vertebrates, we show that many ion channels underlying these functions underwent adaptive evolution during the transition from water to land. Our findings suggest that adaptive changes in ion channels helped vertebrates acquire the physiological capabilities needed to survive and diversify on land, providing new insight into the molecular basis of one of the greatest phenotypic transformations in vertebrate evolution.

evolutionary biology↗

bioRxiv2026

Mechanosensitive channels dominate the minimal ion channelrepertoire in prokaryotes

The eukaryotic genomes encode hundreds of proteins that function as ion channels and transporters. Essential for sustaining life, these proteins mediate the movement of inorganic ions (e.g., K+, Na+, Cl-, and Ca2+) across the plasma membrane according to their electrochemical gradients. In multicellular organisms, a diverse array of ion channels contributes to the maintenance of the resting membrane potential, the regulation of pH, osmolarity, and cell volume, and the control of secretion, electrical excitability, and synaptic activity, among many other fundamental physiological processes. Although independent evolutionary origins have been proposed for several ion channel families, their relative hierarchical importance for cellular viability remains poorly understood. To advance our knowledge of ion channel evolutionary history, we focused on determining the minimal combination of permeabilities that allows cellular viability. To this end, we conducted a survey of representative prokaryotes with small genomes across bacterial and archaeal phyla. By focusing on the smallest genomes, our approach enabled the identification of five ion channel architectures shared among prokaryotes. Among these, non-selective mechanosensitive channels (MscS and MscL) are the most abundant, followed by CLC-type channels, RCK-containing 2TM potassium channels, and proton channels of the MotA/TolQ/ExbB family. The conservation of the mechanosensitive protein architecture across archaeal and bacterial membranes suggests that the capacity to monitor physical membrane integrity predates the requirements for electrical communication.

biophysics↗

bioRxiv2025

An Evolutionary Novelty in TRPV1 Functional Regulation: Characterization of a Dominant-Negative Isoform Exclusive to Catarrhine Primates

TRPV1, a member of the transient receptor potential (TRP) family, is a non-selective cation channel primarily known for its role in pain perception, inflammation, and thermosensation. In mammals, it responds to noxious heat (>43{degrees}C) and chemical stimuli such as capsaicin and protons. It is widely expressed in sensory neurons, notably in the dorsal root and trigeminal ganglia. However, it is also found in some non-neuronal tissues, like the skin and bladder. The human canonical variant of TRPV1 renders a protein with 839 residues. Different splice variants have been described, and some display a dominant negative effect, partially or totally inhibiting the activity of the canonical counterpart. Here, we characterize a splice variant that encodes for a channel of 850 amino acids (TRPV1850). This variant is an evolutionary novelty of catarrhine (Old World monkeys and apes) primates, incorporating an exon of 33 bp long. Both imaging of membrane expression and electrophysiological recordings suggest that TRPV1850 alone does not reach the plasma membrane. However, in cells co-expressing the canonical and TRPV1850 variants, the latter would act as a dominant negative, preventing the canonical variant from reaching the plasma membrane and rendering smaller macroscopic currents in response to capsaicin. Thus, this new isoform of the TRPV1 ion channel represents a novel form of functional regulation only present in apes and Old World monkeys. SignificanceWe identified a novel isoform of the TRPV1 ion channel, a protein essential for detecting pain and heat stimuli unique to apes and Old World monkeys. This isoform contains an additional exonic sequence encoding eleven amino acids, which originated in the common ancestor of apes and Old World monkeys. This additional exonic sequence disrupts a specific domain in the N-terminal region of the protein, resulting in functional differences. Unlike the canonical TRPV1 isoform, this variant cannot reach the plasma membrane independently. Instead, it exerts a dominant-negative effect by interfering with the canonical TRPV1 protein, reducing its ability to localize to the cell surface and diminishing its responsiveness to capsaicin, a well-known TRPV1 activator.

evolutionary biology↗

bioRxiv2024

Interspecies relationships of wild amoebae and bacteria with C. elegans create environments propitious for multigenerational diapause.

The molecular and physical communication within the microworld supports the entire web of life as we know it. How organisms such as bacteria, amoeba and nematodes -all superabundant-interact to sustain their niche, however, is not known, especially how their associations generate and affect behavior of animals in fluctuating environments. To have a frame to study interactions between microbe and animal, we collected soil from a temperate semi-arid climate and isolated the culturable genus of bacteria Comamonas, Stenotrophomonas, Chryseobacterium and Rhodococcus and the amoeba Tetramitus. This ensemble was then fed in long-term experiments to the nematode C. elegans to study developmental rate, diapause entry, fertility, feeding behavior and neuronal integrity. We observed that the ensemble is long lasting and induces animals to diapause after a few generations under conditions that are not canonically pathogenic. We called this phenomenon Dauer Formation in Natural Ensembles (DaFNE). DaFNE requires the communication between live bacteria and the nematode intestine, suggesting the existence of a bidirectional interaction in the holobiont. While all bacteria from the ensemble colonize the intestine of the nematodes, Comamonas is the most represented and Rhodococcus the scarcest. The amoeba Tetramitus can be ingested by C. elegans, but it is not part of its microbiota. DaFNE depends on pheromone and nematode quorum, but high temperature in the homeostatic range, triggers diapause with fewer numbers. DaFNE increases as generations pass and is also remembered transgenerationally. The RNA interference (RNAi) pathway is needed for initiation of DaFNE, indicating the communication via RNA is crucial to execute bacterially induced behaviors in natural environments. SignificanceMicrobes have an overwhelming influence over the animals they live with, modulating development and decision making. Microscopic nematodes are the most abundant multicellular animals in the biosphere, suggesting they possess well-rehearsed successful relationships with their associated microbiota. Little is known about the modulation of nematode behavior in complex ecosystems with multiple organisms interacting. We use bacteria and amoeba from a natural ecosystem and introduce the pioneer nematode C. elegans to study behavioral parameters in long lasting experiments. The most striking response of nematodes to this natural environment is the commitment to diapause of a significant portion of the population. We call this form of hibernation Dauer Formation in Natural Ensembles or DaFNE. We propose that animals in nature may hibernate frequently, as a result of the communication with their natural biota. We find that DaFNE requires pheromone production in nematodes and also the RNA interference pathway, suggesting the RNA repertoire of both entities may be at play. Higher temperatures in the optimal range for nematode growth, require much less nematode quorum for DaFNE, indicating that a non-noxious increase in temperature favors diapause in natural environments. Nematodes respond to each bacterium in different ways when grown in monocultures and in the ensemble. This suggests that the abundance of specific species in nature may shift behavioral preferences and outputs in microscopic animals. We also show that the amoeba Tetramitus can be ingested by worms, demonstrating that C. elegans is a broader microbivore. Like worms, amoebae display specific responses to bacteria and add variability to behaviors elicited by nematodes. Finally, bacteria in the ensemble unlike in monocultures, are not exhausted during the length of the experiments even in the presence of bacterivore nematodes and amoebae.

microbiology↗

bioRxiv2023

Evolution of ion channels in cetaceans a natural experiment in the tree of life

Cetaceans could be seen as a natural experiment within the tree of life in which a mammalian lineage changed from terrestrial to aquatic habitats. This shift involved extensive phenotypic modifications, which represent an opportunity to explore the genetic bases of phenotypic diversity. Furthermore, the availability of whole genome sequences in representative species of all main cetacean groups means that we are in a golden age for such studies. Among the different molecular systems that maintain cellular homeostasis, ion channels are crucial for the proper physiological functioning of all living species. This study aims to explore the evolution of ion channels during the evolutionary history of cetaceans. To do so, we created a bioinformatic pipeline to annotate the repertoire of ion channels in the genome of the species included in our sampling. Our main results show that cetaceans have on average, fewer protein-coding genes and a higher percentage of annotated ion channels than non-cetacean mammals. Signals of positive selection were detected in ion channels related to the heart, locomotion, visual and neurological phenotypes. Interestingly, we predict that the NaV1.5 ion channel of most toothed whales (odontocetes) is sensitive to tetrodotoxin (TTX), similar to NaV1.7, given the presence of tyrosine instead of cysteine, in a specific position of the ion channel. Finally, the gene turnover rate of the cetacean crown group is more than three times faster than non-cetacean mammals.

evolutionary biology↗

bioRxiv2020

Mutations on a novel brain-specific isoform of PGC1α leads to extensive upregulation of neurotransmitter-related genes and sexually dimorphic motor deficits in mice

The peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC1) is known as a transcriptional co-activator in peripheral tissues but its function in the brain remains poorly understood. Various brain-specific Pgc1 isoforms have been reported in mice and humans, including transcripts derived from a novel promoter about [~]580 Kb upstream from the reference gene. These isoforms incorporate repetitive sequences from the simple sequence repeat (SSR) and short interspersed nuclear element (SINE) classes and are predicted to give rise to proteins with distinct amino-termini. In this study, we show that a SINE-containing isoform is the predominant form of Pgc1 expressed in neurons. We then generated a mouse carrying a mutation within the SINE to study its functional role in the brain. By combining genomics, biochemical and behavioural approaches, we show that this mutation leads to impaired motor coordination in females, but not male mice, associated with the upregulation of hundreds of cerebellar genes. Moreover, our analysis suggests that known nuclear receptors interact with this isoform of PGC1 in the brain to carry out the female transcriptional program. These data expand our knowledge on the role of Pgc1 in the brain and help explain its conflicting roles in neurological disease and behavioural outcomes.

neuroscience↗

bioRxiv2018

Mitochondrial acetyl-CoA reversibly regulates locus-specific histone acetylation and gene expression

The impact of mitochondria in epigenetics is emerging but our understanding of this relationship and its impact on gene expression remain incomplete. We previously showed that acute mitochondrial DNA (mtDNA) loss leads to histone hypoacetylation. It remains to be defined if these changes are maintained when mitochondrial dysfunction is chronic and, importantly, if they are sufficient to alter gene expression. To fill these gaps, we here studied both a progressive and a chronic model of mtDNA depletion using biochemical, pharmacological, genomics and genetic assays. We show that histones are hypoacetylated in both models. We link these effects to decreased histone acetyltransferase (HAT) activity independent of changes in ATP citrate lyase function, which can be reversibly modulated by altering specifically the mitochondrial pool of acetyl-CoA. Also, we determined that these changes regulate locus-specific gene expression and physiological outcomes, including the production of prostaglandins. These results may be relevant to the pathophysiology of mtDNA depletion syndromes and to understanding the effects of environmental agents, such as AZT or antibiotics, that lead to physical or functional mtDNA loss.

genomics↗