Biology subjects

Opazo, J. C.

Publications and source records attributed to Opazo, J. C..

At least 19 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↗

bioRxiv2026

RNA-DNA triplex-forming miRNAs define an evolutionarily recent chromatin regulatory mechanism

MicroRNAs (miRNAs) are best known for their role in post-transcriptional gene regulation in the cytoplasm. However, a subset of miRNAs has been detected in the nucleus, suggesting additional regulatory functions. Here, we systematically characterize chromatin-associated small non-coding RNAs in the human pancreatic cancer cell line PANC-1. Using chromatin RNA immunoprecipitation coupled with small RNA sequencing, we show that the chromatin-associated small RNA population differs markedly from the bulk nuclear RNA pool and is strongly enriched in miRNAs. Among these, miR-21 represents the most abundant chromatin-associated species. Sequence analyses revealed that a subset of these miRNAs fulfills the requirements for RNA-DNA triplex formation at genomic regulatory regions. Gel-shift assays further demonstrate that Argonaute2 (Ago2) directly interacts with triple-helical nucleic acid structures in vitro, suggesting a potential mechanistic link between triplexes and Ago2-chromatin engagement. Evolutionary analyses indicate that these triplex-forming chromatin-associated miRNAs are largely restricted to anthropoid primates, in contrast to broadly conserved non-triplex-forming miRNAs. Together, our results identify a population of chromatin-associated miRNAs and provide evidence for a potential structural mechanism linking miRNAs, Ago2, and chromatin.

molecular biology↗

bioRxiv2026

Evolutionary history and functional divergence of hydroxycarboxylic acid receptors in primates

Hydroxycarboxylic acid receptors (HCARs) are class A G-protein-coupled receptors that function as metabolic sensors. This receptor family includes three members (HCAR1, HCAR2, and HCAR3) expressed in metabolically active tissues and immune cells, where they link cellular metabolic status to physiological responses. This study aims to elucidate the evolutionary history of the most recently originated members of the HCAR gene family, namely HCAR2 and HCAR3, in primates. According to our phylogenetic analyses, the duplicative history of these genes involved multiple independent duplication events during ape evolution. Thus, most ape lineages possess independently originated duplicated copies, while non-ape primates retain the ancestral condition of a single-copy gene (HCAR2/3). Our analyses further indicate that this single-copy gene in non-ape primates is functionally equivalent to HCAR2, suggesting that the primary functional innovation in apes is associated with the physiological roles of HCAR3. Finally, gene expression analyses reveal that major divergence in tissue expression occurred after the initial duplication event that generated HCAR1 and the HCAR2/3 lineage, whereas HCAR2 and HCAR3 exhibit substantial overlap in their expression profiles. Thus, the more refined and context-dependent regulation of lipid metabolism that provides the HCAR3 receptor seems to have originated multiple times during the evolutionary history of apes.

evolutionary biology↗

bioRxiv2025

A Deep Dive into the Globin Superfamily of Sharks, Skates, and Rays: Contrasting patterns of gene loss and retention relative to bony vertebrates

The globin gene superfamily encodes oxygen-binding proteins that are present in all domains of life. Hemoglobins and myoglobins of jawed vertebrates are among the most well-studied proteins in the context of structure-function relationships and evolution after gene duplication. However, these studies have primarily focused on bony vertebrates, and research on globin gene evolution in cartilaginous fish has been limited by a lack of genomic resources. In this study, we leverage newly available cartilaginous fish genomes to investigate globin gene family evolution across skates, rays, sharks, and sawfish. We found that, when present, most globin genes are in a single copy, with androglobin, globin-Y, and myoglobin present in all cartilaginous fish, while the two globin-X genes were differentially retained between the Holocephali and sharks, skates, and rays. Neuroglobin appears to have been lost at the common ancestor of all cartilaginous fish. The - and {beta}-globin gene subfamilies underwent independent expansions in different lineages of cartilaginous fish. Most cartilaginous fish globins have conserved synteny with other jawed vertebrates except myoglobin. Additionally, NPRL3, which directly flanks the hemoglobin clusters of other jawed and jawless vertebrates and regulates hemoglobin gene expression, is on a separate chromosome from the hemoglobin clusters of cartilaginous fish. When we examined globin gene expression patterns across cartilaginous fish tissues and developmental stages, we found that most globins are expressed as expected compared to other jawed vertebrates. However, hemoglobin paralogs are more widely expressed in embryonic tissues compared to later-stage tissues in cases where many copies exist. Our results reveal similar and contrasting patterns of globin gene evolution between cartilaginous and bony vertebrates and shed light on the early stages of globin gene evolution in gnathostomes. Significance StatementThe evolution of the globin gene family in jawed vertebrates is of significant interest; however, most studies have been limited to bony vertebrates. With the influx of new publicly available cartilaginous fish genomes, we conducted the most comprehensive analysis of globin gene evolution in cartilaginous fish to date using phylogenetic, structural, and transcriptomic analyses. Our results shed light on similar and contrasting patterns of globin-gene evolution between cartilaginous and bony vertebrates and provide insight into the early evolution of globins in jawed vertebrates. Key-words: Globins, Cartilaginous Fish, Chondrichthyes, Gene Family Evolution

evolutionary biology↗

bioRxiv2025

Coordinated adaptive changes in insulin, insulin receptor, and inceptor genes in hystricognath rodents

Insulin is a central regulator of glycemia and is highly conserved across mammals. However, hystricognath rodents represent a notable exception, exhibiting insulin proteins that diverge significantly in both sequence and physiological function. Previous studies have shown that this divergence is partially driven by positive selection acting on residues involved in the second binding site of the hormone and in hexamer formation, which is critical for insulin storage in mammals. Inceptor (encoded by the gene ELAPOR1) is a recently discovered regulator of the insulin pathway that interacts with proinsulin, insulin, the Insulin receptor (Insr), and the Insulin-like growth factor 1 receptor (Igf1r). Inceptor functions within pancreatic {beta}-cells, where it promotes clathrin-mediated endocytosis of Insr and directs cytoplasmic insulin and proinsulin to lysosomal degradation. Using a comprehensive dataset of mammalian sequences, we tested for positive selection in the genes Ins, Insr, Igf1r, and ELAPOR1 using maximum likelihood models. Significant signals of positive selection were detected in hystricognath rodents for Ins, Insr, and ELAPOR1, but not for Igf1r. In Ins, positively selected sites were concentrated in the second binding site and in regions involved in hexamer formation, along with an additional site in the C-peptide. In Insr, selected sites were primarily located in the ectodomain, particularly in regions that interact with the second binding site of the insulin molecule. In ELAPOR1, selected sites were concentrated in the signal peptide and at the boundary between the second cysteine-rich domain and the mannose 6-phosphate receptor region. Together, these findings provide strong evidence that natural selection has shaped multiple components of the insulin signaling pathway, contributing to the functional divergence observed in hystricognath rodents.

evolutionary biology↗

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

Evolutionary and Functional Analysis of Monoamine Oxidase C (MAO C): A Novel Member of the MAO Gene Family

The monoamine oxidase (MAO) gene family encodes for enzymes that perform the oxidative deamination of monoamines, a process required to degrade norepinephrine, serotonin, dopamine, and other amines. While mammalian MAO enzymes, MAO A and MAO B, have been extensively studied, the molecular properties of the other family members are only partly uncovered. This study aims to explore the evolution of monoamine oxidases, emphasizing understanding the MAO gene repertoire among vertebrates. Our analyses show that the duplication that gave rise to MAO A and MAO B occurred in the ancestor of tetrapods, between 408 and 352 million years ago. Non-tetrapod jawed vertebrates possess the ancestral preduplicative condition of MAO A/B. Our results also identified a new family member, MAO C, in non-tetrapod jawed vertebrates. Thus, most jawed vertebrates possess a repertoire of two MAO genes, MAO A and MAO B in tetrapods and MAO A/B and MAO C in non-tetrapod jawed vertebrates, representing different MAO gene lineages. Jawless vertebrates possess the ancestral condition of a single copy gene, MAO A/B/C. Enzymatic assays conducted on the MAO recombinant enzymes of the Indo-Pacific tarpon show that both proteins, MAO A/B and MAO C, have enzymatic and molecular properties more similar to human MAO A, with the former featuring a strikingly higher activity rate when compared to all other MAO enzymes. Our analyses underscore the importance of scanning the tree of life for new gene lineages to understand phenotypic diversity and gain detailed insights into their function.

evolutionary biology↗

bioRxiv2023

Extreme high-elevation mammal surveys reveal unexpectedly high upper range limits of Andean mice

In the worlds highest mountain ranges, uncertainty about the upper elevational range limits of alpine animals represents a critical knowledge gap regarding the environmental limits of life and presents a problem for detecting range shifts in response to climate change. Here we report results of mountaineering mammal surveys in the Central Andes, which led to the discovery of multiple species of mice living at extreme elevations that far surpass previously assumed range limits for mammals. We live-trapped small mammals from ecologically diverse sites spanning >6700 m of vertical relief, from the desert coast of northern Chile to the summits of the highest volcanoes in the Andes. We used molecular sequence data and whole-genome sequence data to confirm the identities of species that represent new elevational records and to test hypotheses regarding species limits. These discoveries contribute to a new appreciation of the environmental limits of vertebrate life.

evolutionary biology↗

bioRxiv2023

Genomic and Radiocarbon Insights into the Mystery of Mouse Mummies on the Summits of >6000 m Andean Volcanoes

Our understanding of the limits of animal life is continually revised by scientific exploration of extreme environments. Here we report the discovery of numerous mummified cadavers of leaf-eared mice, Phyllotis vaccarum, from the summits of three different Andean volcanoes at elevations 6029-6233 m (19,780-20,449 ft) above sea level in the Puna de Atacama (Chile-Argentina). Such extreme elevations were previously assumed to be completely uninhabitable by mammals. In combination with a live-captured specimen of the same species from the nearby summit of Volcan Llullaillaco (6739 m [=22,110 ft]), the 13 summit mummies represent the highest physical records of mammals in the world. We report a chromosome-level genome assembly for P. vaccarum in combination with a whole-genome re-sequencing analysis and radiocarbon dating analysis that provide insights into the provenance and antiquity of the summit mice. We test alternative hypotheses to explain the existence of mouse graveyards on the summits of Atacama volcanoes. Radiocarbon data indicate that the most ancient of the mummies were at most a few centuries old. Genomic polymorphism data revealed a high degree of continuity between the summit mice and conspecifics from lower elevations in the surrounding Altiplano. Genomic data also revealed equal numbers of males and females among the summit mice and evidence of close kinship between some individuals from the same summit groups. These findings bolster evidence for self-sustaining populations of Phyllotis at elevations >6000 m and challenge assumptions about the environmental limits of vertebrate life and the physiological tolerances of small mammals.

evolutionary biology↗

bioRxiv2021

Sequence conservation and structural features that are common within TRP channels

TRP proteins are a large family of cation selective channels, surpassed in variety only by voltage-gated potassium channels. Detailed molecular mechanisms governing how membrane voltage, ligand binding, or temperature can induce conformational changes promoting the open state of the channel are still missing for TRP channels. Aiming to unveil distinctive structural features common to the transmembrane domains within the TRP family, we performed bioinformatic analyses over a large set of TRP channel genes. Here we report a discrete and exceptionally conserved set of residues. This fingerprint is composed of eleven residues localized at equivalent three-dimensional positions in TRP channels from the different subtypes. Moreover, these amino acids are arranged in three groups, connected by a set of aromatics located at the core of the transmembrane structure. We hypothesize that differences in the connectivity between these different groups of residues harbors the apparent differences in coupling strategies used by TRP subgroups.

evolutionary biology↗

bioRxiv2021

Whole genome duplications and the diversification of the Globin-X genes of vertebrates

The globin superfamily of vertebrate genes is a textbook example of how the interplay between local gene duplications, whole-genome duplications, and regulatory changes can facilitate the evolution of novel protein functions. Almost every vertebrate examined possesses copies of hemoglobin and myoglobin in their genomes, and both cytoglobin and neuroglobin are present in the vast majority of vertebrate genomes surveyed as well. The phylogenetic distribution of globin-E, globin-Y and globin-X (GbX), however, is more spotty, suggesting multiple independent gene losses. Globin-X is an enigmatic globin with a wide phyletic distribution that spans protostomes and deuterostomes. Unlike canonical globins such as hemoglobins and myoglobins, functional data suggest that GbX does not have a primary respiratory function. Instead, available evidence suggests that GbX may play a role in protecting cells from oxidative damage and in reducing nitrite and it is predicted to be bound to the cell membrane. Recently released genomes from key vertebrate taxa provide an excellent opportunity to address questions about the early stages of evolution of these genes in vertebrates. In the current study, we integrate bioinformatic, synteny and phylogenetic analyses to characterize the diversity of GbX genes in non-teleost ray-finned fishes, resolve relationships between the GbX genes of cartilaginous fish and the GbX genes of bony vertebrates, and demonstrate that the GbX genes of cyclostomes and gnathostomes have independent duplicative histories. Our study highlights the role that whole genome duplications (WGDs) have played in expanding the repertoire of genes in vertebrate genomes. Our results indicate that GbX paralogs have a remarkably high rate of retention following WGDs in comparison to other globin genes, and also provide an evolutionary framework for interpreting results of experiments that examine functional properties of GbX and patterns of tissue-specific expression. By identifying GbX genes products of different WGDs in the vertebrate tree of life, our results can guide the design of experimental work to explore whether gene duplicates that originate via WGDs have evolved novel functional properties or expression profiles relative to singleton or tandemly duplicated copies of GbX.

evolutionary biology↗

bioRxiv2021

Independent origins of the Golgi phosphoprotein 3 oncoprotein gene

Golgi phosphoprotein 3 (GOLPH3) was the first reported oncoprotein of the Golgi apparatus. It was identified as an evolutionarily conserved protein upon its discovery about 20 years ago, but its function remains puzzling in normal and cancer cells. The GOLPH3 gene is part of a group of genes that also includes the GOLPH3L gene. Because cancer has deep roots in multicellular evolution, studying the evolution of the GOLPH3 gene family in non-model species represents an opportunity to identify new model systems that could help better understand the biology behind this group of genes. The main goal of this study is to explore the evolution of the GOLPH3 gene family in birds as a starting point to understand the evolutionary history of this oncoprotein. We identified a repertoire of three GOLPH3 genes in birds. We found duplicated copies of the GOLPH3 gene in all main groups of birds other than paleognaths, and a single copy of the GOLPH3L gene. We suggest there were at least three independent origins for GOLPH3 duplicates. Amino acid divergence estimates show that most of the variation is located in the N-terminal region of the protein. Our transcript abundance estimations show that one paralog is highly and ubiquitously expressed, and the others were variable. Our results are an example of the significance of understanding the evolution of the GOLPH3 gene family, especially for unraveling its structural and functional attributes.

evolutionary biology↗

bioRxiv2020

Phylogenetic diversification of sirtuin genes with a description of a new family member

Studying the evolutionary history of gene families is a challenging and exciting task with a wide range of implications. In addition to exploring fundamental questions about the origin and evolution of genes, disentangling their evolution is also critical to those who do functional/structural studies to allow a deeper and more precise interpretation of their results in an evolutionary context. The sirtuin gene family is a group of genes that are involved in a variety of biological functions mostly related to aging. Their duplicative history is an open question, as well as the definition of the repertoire of sirtuin genes among vertebrates. Our results show a well-resolved phylogeny that represents an improvement in our understanding of the duplicative history of the sirtuin gene family. We identified a new sirtuin gene family member (SIRT3.2) that was apparently lost in the last common ancestor of amniotes but retained in all other groups of jawed vertebrates. According to our experimental analyses, elephant shark SIRT3.2 protein is located in mitochondria, the overexpression of which leads to an increase in cellular levels of ATP. Moreover, in vitro analysis demonstrated it has deacetylase activity being modulated in a similar way to mammalian SIRT3. Our results indicate that there are at least eight sirtuin paralogs among vertebrates and that all of them can be traced back to the last common ancestor of the group that existed between 676 and 615 millions of years ago.

evolutionary biology↗

bioRxiv2020

Phylogenetic analyses suggest independent origins for trichromatic color vision in apes and Old World monkeys

In catarrhine primates, trichromatic color vision is associated with the presence of three opsin genes that absorb light at three different wavelengths. The OPN1LW and OPN1MW genes are found on the X chromosome. Their proximity and similarity suggest that they originated from a duplication event in the catarrhine ancestor. In this study we use the primate genomes available in public databases to study the duplicative history of the OPN1LW and OPN1MW genes and characterize their spectral sensitivity. Our results reveal a phylogenetic tree that shows a clade containing all X-linked opsin paralogs found in Old World monkeys to be related to a clade containing all X-linked opsin paralogs identified in apes, suggesting that routine trichromacy originated independently in apes and Old World monkeys. Also, we found spectral variability in the X-linked opsin gene of primates. Our study presents a new perspective for the origin of trichromatic color vision in apes and Old World monkeys, not reported so far.

genomics↗

bioRxiv2020

Discovery of the world's highest-dwelling mammal

Environmental limits of animal life are invariably revised upwards when the animals themselves are investigated in their natural habitats. Here we report results of a scientific mountaineering expedition to survey the high-altitude rodent fauna of Volcan Llullaillaco in the Puna de Atacama of northern Chile, an effort motivated by video documentation of mice (genus Phyllotis) at a record altitude of 6205 m. Among numerous trapping records at altitudes >5000 m, we captured a specimen of the yellow-rumped leaf-eared mouse (Phyllotis xanthopygus rupestris) on the very summit of Llullaillaco at 6739 m. This summit specimen represents an altitudinal world record for mammals, far surpassing all specimen-based records from the Himalayas and elsewhere in the Andes. This discovery suggests that we may have generally underestimated the altitudinal range limits and physiological tolerances of small mammals simply because the worlds highest summits remain relatively unexplored by biologists.

evolutionary biology↗

bioRxiv2020

Positive selection and fast turnover rate in tumor suppressor genes reveal how cetaceans resist cancer

Cetaceans are the longest-living species of mammals and the largest in the history of the planet. They have developed mechanisms against diseases such cancer, although the underlying molecular bases of these remain unknown. The goal of this study was to investigate the role of natural selection in the evolution of 1077 tumour suppressor genes (TSGs) in cetaceans. We used a comparative genomic approach to analyse two sources of molecular variation in the form of dN/dS rates and gene copy number variation. We found a signal of positive selection in the ancestor of cetaceans within the CXCR2 gene, an important regulator of DNA-damage, tumour dissemination, and immune system. Further, in the ancestor of baleen whales, we found six genes exhibiting positive selection relating to such diseases as breast carcinoma, lung neoplasm (ADAMTS8) and leukaemia (ANXA1). The TSG turnover rate (gene gain and loss) was almost 2.4-fold higher in cetaceans as compared to other mammals, and noticeably even faster in baleen whales. The molecular variants in TSGs found in baleen whales, combined with the faster gene turnover rate, could have favoured the evolution of their particular traits of anti-cancer resistance, gigantism and longevity. Additionally, we report 71 genes with duplications, of which 11 genes are linked to longevity (e.g. NOTCH3 and SIK1) and are important regulators of senescence, cell proliferation and metabolism. Overall, these results provide evolutionary evidence that natural selection in tumour suppressor genes could act on species with large body sizes and extended life span, providing novel insights into the genetic basis of disease resistance.

evolutionary biology↗

bioRxiv2019

Evolution of the DAN gene family in vertebrates

The DAN gene family (DAN, Differential screening-selected gene Aberrant in Neuroblastoma) is a group of genes that is expressed during development and plays fundamental roles in limb bud formation and digitation, kidney formation and morphogenesis and left-right axis specification. During adulthood the expression of these genes are associated with diseases, including cancer. Although most of the attention to this group of genes has been dedicated to understanding its role in physiology and development, its evolutionary history remains poorly understood. Thus, the goal of this study is to investigate the evolutionary history of the DAN gene family in vertebrates, with the objective of complementing the already abundant physiological information with an evolutionary context. Our results recovered the monophyly of all DAN gene family members and divide them into five main groups. In addition to the well-known DAN genes, our phylogenetic results revealed the presence of two new DAN gene lineages; one is only retained in cephalochordates, whereas the other one (GREM3) was only identified in cartilaginous fish, holostean fish, and coelacanth. According to the phyletic distribution of the genes, the ancestor of gnathostomes possessed a repertoire of eight DAN genes, and during the radiation of the group GREM1, GREM2, SOST, SOSTDC1, and NBL1 were retained in all major groups, whereas, GREM3, CER1, and DAND5 were differentially lost.

evolutionary biology↗