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Insights Into the Skin of Caecilian Amphibians from Gene Expression Profiles María Torres-Sánchez1,2* , Mark Wilkinson3, David J

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Insights Into the Skin of Caecilian Amphibians from Gene Expression Profiles María Torres-Sánchez1,2* , Mark Wilkinson3, David J Torres-Sánchez et al. BMC Genomics (2020) 21:515 https://doi.org/10.1186/s12864-020-06881-8 RESEARCH ARTICLE Open Access Insights into the skin of caecilian amphibians from gene expression profiles María Torres-Sánchez1,2* , Mark Wilkinson3, David J. Gower3, Christopher J. Creevey4 and Diego San Mauro1 Abstract Background: Gene expression profiles can provide insights into the molecular machinery behind tissue functions and, in turn, can further our understanding of environmental responses, and developmental and evolutionary processes. During vertebrate evolution, the skin has played a crucial role, displaying a wide diversity of essential functions. To unravel the molecular basis of skin specialisations and adaptations, we compared gene expression in the skin with eight other tissues in a phylogenetically and ecologically diverse species sample of one of the most neglected vertebrate groups, the caecilian amphibians (order Gymnophiona). Results: The skin of the five studied caecilian species showed a distinct gene expression profile reflecting its developmental origin and showing similarities to other epithelial tissues. We identified 59 sequences with conserved enhanced expression in the skin that might be associated with caecilian dermal specialisations. Some of the up- regulated genes shared expression patterns with human skin and potentially are involved in skin functions across vertebrates. Variation trends in gene expression were detected between mid and posterior body skin suggesting different functions between body regions. Several candidate biologically active peptides were also annotated. Conclusions: Our study provides the first atlas of differentially expressed sequences in caecilian tissues and a baseline to explore the molecular basis of the skin functions in caecilian amphibians, and more broadly in vertebrates. Keywords: Bioactive peptides, Claudins, Cornified proteins, Gymnophiona, Keratins, Transcriptomics Background should provide insight into the evolutionary history of di- Most nucleated cells of a multicellular organism contain versification and adaptation [3, 4]. Data on tissue-specific the same genetic information, with the functional diversity gene expression have been massively boosted by the appli- of different organs and tissues mainly caused by differ- cation of high throughput sequencing (HTS) technologies ences in gene expression and regulation. Gene expression in, mainly, epigenomics, transcriptomics, and proteomics. profiles of a tissue of an organism may vary with ontogeny The outer tissue of vertebrate animals, the skin, is and in response to environmental conditions, with differ- formed by multiple cell layers that are in the frontline of ences between tissues reflecting their specialised functions direct interactions with both abiotic and biotic compo- [1, 2]. Tissue-specific gene expression profiles are also ex- nents of the environment. The skin is one of the largest pected to differ among species, underpinning interspecific organs in vertebrates, and is involved in multiple vital phenotypic variation. Comparisons of these profiles functions including protection, defence, communication, and reproduction. This functional diversity is coupled with various specialised structures in different taxa, in- * Correspondence: [email protected] 1Department of Biodiversity, Ecology and Evolution, Complutense University cluding glands, pigment cells, scales, claws, horns, of Madrid, 28040 Madrid, Spain feathers and fur [5, 6]. In amphibians, the skin is often a 2 Present address: Department of Biology, University of Florida, Gainesville, moist, relatively thin, permeable tissue with keratinisa- Florida 32611, USA Full list of author information is available at the end of the article tion mainly in the outermost cell layer (stratum © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Torres-Sánchez et al. BMC Genomics (2020) 21:515 Page 2 of 9 corneum) of the epidermis and with diverse exocrine expression levels were identified: (i) R. bivittatum (mid- glands distributed in the dermis [7, 8]. Mucous glands body Skin9 and midbody Skin79), M. unicolor (midbody play an important role in transitions between aquatic Skin8 and midbody Skin82), and M. dermatophaga and terrestrial environments by helping to prevent dehy- (midbody Skin80 and posterior region PosteriorSkin80) dration [9]. Mucus also facilitates cutaneous respiration samples; and (ii) M. unicolor (posterior region Posterior- [10], locomotion and escape from predators [7, 11]. Skin82), C. tentaculata (midbody Skin81 and posterior Granular glands can produce cocktails of diverse bio- region PosteriorSkin81), and T. compressicauda (mid- logically active compounds, some of which are essential body Skin83 and posterior region PosteriorSkin83) sam- for defence and communication [12, 13], such as anti- ples. Both of these skin groups were however clustered microbial peptides (AMPs) and pheromones. with samples from other tissue types. The first skin Caecilians (order Gymnophiona) are relatively poorly group was found in two related clusters, in which the M. known, snake-like, mainly tropical amphibians. Adults of dermatophaga midbody sample (Skin80) was more simi- most caecilian species live in soils and features associ- lar to muscle tissues (cardiac: Heart83, and skeletal: ated with their fossorial lifestyle include elongate limb- Muscle81, Muscle79 and Muscle82). The second skin less bodies, reduced eyes and a pair of sensory tentacles group was clustered with the lung sample from T. com- on the snout [14, 15]. Caecilian skin is annulated, with pressicauda (Lung83) that was highly correlated with dermal folds that, in many species, hide dermal scales, a both of the skin samples of the same species (Skin83 unique specialisation among extant tetrapods the func- and PosteriorSkin83). Samples were classified also by the tion of which is not well-understood [16–18]. In some decomposition of their variance with the first six princi- caecilian species, the maternal skin periodically stores pal components (PCs) of the PCA together explained lipid reserves to provide nutrition to dermatophagous 45.15% (= 16.32 + 6.67 + 6.33 + 5.66 + 5.16 + 5.01) of the hatchlings [19–21]. total variance of the gene expression, and with each sub- Molecular characterisation of caecilian skin features sequent component explaining less than 5% of the ex- and functions is scarce. Preliminary studies of multi- pression variance. The first three components grouped tissue transcriptomes from five species of caecilians the samples per species (Fig. S1). Skin samples were identified candidate novel gene families with skin- clustered toward positive values of PC4 (Fig. 1b). Lung specific expression [22], and a skin collagen gene and foregut samples were the most similar tissue sam- (col17a1) that has been under positive selection in the ples to skin along PC4, and liver samples the most dis- branch subtending the studied species [23]. Given the similar, distributed toward high negative values along distinctiveness of caecilian skin, a thorough characterisa- PC4. tion of tissue-specific gene expression profiles could re- We identified 246 sequences with differential expres- veal the molecular machinery behind skin functions that sion in caecilian skin in the analysis comprising the 40 potentially played a crucial role in the adaptation of the tissues (see Fig. 2 and Additional file 2). Among these group. To identify genes with conserved expression pat- sequences, 59 were identified as up-regulated or skin terns in the skin across the five studied caecilian species enriched sequences (see Fig. 2 and Table S3) with 12 of (Rhinatrema bivittatum [Guérrin-Méneville, 1838], Cae- these having a positive fold change greater than four cilia tentaculata Linnaeus, 1758, Typhlonectes compres- units (atp13a4, bpifc, cldn4, dlx3, fat2, krt75, krt80, sicauda [Duméril & Bibron, 1841], Microcaecilia pou3f1, plca, tfap2c, tfap2e, and znf750). These se- unicolor [Duméril, 1861] and Microcaecilia dermato- quences were found also up-regulated with high fold phaga Wilkinson, Sherratt, Starace & Gower, 2013), we change in the analysis using only tissues from the same conducted a differential expression analysis comparing sequencing company, while down-regulated sequences caecilian skin samples to other tissue samples, and anno- varied depending on the tissues included in the differen- tated skin bioactive peptides using the same multi-tissue tial expression analysis (see Additional
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