Peripheral and central employment of acid-sensing ion channels during early bilaterian evolution
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This work examines the evolutionary origins of acid-sensing ion channels (ASICs), a class of pH-sensing receptors expressed throughout the brain and body. By combining analysis of sequences, functional measurements, and measures of tissue distribution, the authors provide solid evidence that ASICs existed far earlier than previously believed. The present data indicate that ASICs emerged after the split between bilaterians (organisms with two-fold symmetry) and Cnidaria (jellyfish, anemones, corals, etc.), approximately 680 million years ago. This evolutionary and functional analysis of ASIC channels across bilaterian lineages provides relevant information about the evolution of nervous and sensory systems.
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Abstract
Nervous systems are endowed with rapid chemosensation and intercellular signaling by ligand-gated ion channels (LGICs). While a complex, bilaterally symmetrical nervous system is a major innovation of bilaterian animals, the employment of specific LGICs during early bilaterian evolution is poorly understood. We therefore questioned bilaterian animals’ employment of acid-sensing ion channels (ASICs), LGICs that mediate fast excitatory responses to decreases in extracellular pH in vertebrate neurons. Our phylogenetic analysis identified an earlier emergence of ASICs from the overarching DEG/ENaC (degenerin/epithelial sodium channel) superfamily than previously thought and suggests that ASICs were a bilaterian innovation. Our broad examination of ASIC gene expression and biophysical function in each major bilaterian lineage of Xenacoelomorpha, Protostomia, and Deuterostomia suggests that the earliest bilaterian ASICs were probably expressed in the periphery, before being incorporated into the brain as it emerged independently in certain deuterostomes and xenacoelomorphs. The loss of certain peripheral cells from Ecdysozoa after they separated from other protostomes likely explains their loss of ASICs, and thus the absence of ASICs from model organisms Drosophila and Caenorhabditis elegans . Thus, our use of diverse bilaterians in the investigation of LGIC expression and function offers a unique hypothesis on the employment of LGICs in early bilaterian evolution.
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eLife assessment
This work examines the evolutionary origins of acid-sensing ion channels (ASICs), a class of pH-sensing receptors expressed throughout the brain and body. By combining analysis of sequences, functional measurements, and measures of tissue distribution, the authors provide solid evidence that ASICs existed far earlier than previously believed. The present data indicate that ASICs emerged after the split between bilaterians (organisms with two-fold symmetry) and Cnidaria (jellyfish, anemones, corals, etc.), approximately 680 million years ago. This evolutionary and functional analysis of ASIC channels across bilaterian lineages provides relevant information about the evolution of nervous and sensory systems.
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Reviewer #1 (Public Review):
The authors set out to study the evolutionary origins of acid-sensing ion channels (ASICs) using phylogenetic analysis of hundreds of ASIC related genes from dozens of diverse organisms. Using subsequent gene expression and biophysical characterization, they provide evidence that ASICs evolved far earlier than previously thought. Based on observation that Cndiaria lack ASICs yet all major forms of Bilaterians possess ASICs, they conclude that ASICs emerged after these two branches diverged, approximately 680 million years ago.
Furthermore, Bilaterians are divided into three groups: Deuterostomes (which include chordates), Xenacoelomorpha and Protostomes. All three of these groups contain functional ASIC sequences. However, the Protostomes are more complicated. These are further subdivided into Spiralla and …
Reviewer #1 (Public Review):
The authors set out to study the evolutionary origins of acid-sensing ion channels (ASICs) using phylogenetic analysis of hundreds of ASIC related genes from dozens of diverse organisms. Using subsequent gene expression and biophysical characterization, they provide evidence that ASICs evolved far earlier than previously thought. Based on observation that Cndiaria lack ASICs yet all major forms of Bilaterians possess ASICs, they conclude that ASICs emerged after these two branches diverged, approximately 680 million years ago.
Furthermore, Bilaterians are divided into three groups: Deuterostomes (which include chordates), Xenacoelomorpha and Protostomes. All three of these groups contain functional ASIC sequences. However, the Protostomes are more complicated. These are further subdivided into Spiralla and Ecdysozoa (which include arthropods). The Spiralla possess functional ASIC sequences while the Ecdysozoa seem to have lost them. The authors suggest this maybe because ASICs were initially expressed in ectodermal ciliated cells where they helped drive locomotion in response to environmental cues and other behaviors. However, when ecdysozoa lost the ectodermal ciliated cells, they also were able to dispense with ASICs, hence modern ecdysoza such as drosophila do not have ASIC sequences.
This work combines several disparate techniques to supply insight into the history of ASIC evolution. The core findings are well supported by the data and will be of general interest to the ASIC community as well as the ligand-gated channel field more broadly. However, the main weakness of the paper is the author's limited discussion of what part(s) of the receptor, if any, are preserved or altered between groups. This work could be much more impactful if the sequences were more thoroughly explored and tied to functional and structural differences.
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Reviewer #2 (Public Review):
In this manuscript, Marti-Solans et al., investigate how ASICs have been employed during early bilaterian evolution. Using thorough phylogenetic investigation of transcriptomes of metazoan DEG/ENaC genes, they identify ASICs through the Bilateria. ASIC genes are present in 3 major bilaterian groups, and absent from all other lineages. With the help of in situ hybridization and electrophysiology they demonstrate anatomical expression and functional properties of diverse ASICs from each major bilaterian lineage. They find that ASIC expression is broader than expected and is present centrally and peripherally, suggesting integrative and sensory roles. By heterologous expression of the ASIC channels of interest in oocytes, they characterize electrophysiological currents to expose that proton activation …
Reviewer #2 (Public Review):
In this manuscript, Marti-Solans et al., investigate how ASICs have been employed during early bilaterian evolution. Using thorough phylogenetic investigation of transcriptomes of metazoan DEG/ENaC genes, they identify ASICs through the Bilateria. ASIC genes are present in 3 major bilaterian groups, and absent from all other lineages. With the help of in situ hybridization and electrophysiology they demonstrate anatomical expression and functional properties of diverse ASICs from each major bilaterian lineage. They find that ASIC expression is broader than expected and is present centrally and peripherally, suggesting integrative and sensory roles. By heterologous expression of the ASIC channels of interest in oocytes, they characterize electrophysiological currents to expose that proton activation properties, Na/K permeability, and inactivation kinetics are diverse across the different lineages. The manuscript is well written, and the results support their conclusions. The results from this study aid the authors in hypothesizing that ASICS were a bilaterian innovation, and, perhaps they were first expressed in the periphery before being incorporated into the brain.
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