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Adaptation and Convergence in Circadian-Related Genes in Iberian Freshwater Fish

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Adaptation and Convergence in Circadian-Related Genes in Iberian Freshwater Fish bioRxiv preprint doi: https://doi.org/10.1101/706713; this version posted June 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 TITLE 2 Adaptation and convergence in circadian-related genes in Iberian freshwater fish 3 4 AUTHORS 5 João M Moreno1, Tiago F Jesus1, Vitor C Sousa1,*,+ and Maria M Coelho1,* 6 AUTHOR AFFILIATIONS 7 1cE3c – Centre for Ecology, Evolution and Environmental Changes, Faculdade de 8 Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal 9 *Shared last authorship. 10 +Corresponding author: Vitor C Sousa, [email protected] 11 1 bioRxiv preprint doi: https://doi.org/10.1101/706713; this version posted June 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 12 ABSTRACT 13 Background 14 The circadian clock is a biological timing system that improves the ability of organisms 15 to deal with environmental fluctuations. At the molecular level it consists of a network 16 of transcription-translation feedback loops, involving genes that activate (bmal and 17 clock – positive loop) and repress expression (cryptochrome (cry) and period (per) – 18 negative loop). This is regulated by daily alternations of light but can also be affected 19 by temperature. Fish, as ectothermic, depend on the environmental temperature and thus 20 are good models to study its integration within the circadian system. Here, we studied 21 the molecular evolution of circadian genes in four Squalius freshwater fish species, 22 distributed across Western Iberian rivers affected by two climatic types with different 23 environmental conditions (e.g. light and temperature). S. carolitertii and S. pyrenaicus 24 inhabit the colder northern region under Atlantic climate type, while S. torgalensis, S. 25 aradensis and some populations of S. pyrenaicus inhabit the warmer southern region 26 affected by summer droughts, under Mediterranean climate type. 27 Results 28 We identified 16 circadian-core genes in the Squalius species using a comparative 29 transcriptomics approach. We detected evidence of positive selection in nine of these 30 genes using methods based on dN/dS. Positive selection was mainly found in cry and 31 per genes of the negative loop of the cycle, with 11 putatively adaptive substitutions 32 mostly located on protein domains. Evidence for positive selection is predominant in 33 southern populations affected by the Mediterranean climate type. By predicting protein 34 features we found that changes at sites under positive selection can impact protein 35 thermostability by changing their aliphatic index and isoelectric point. Additionally, in 36 nine genes, the phylogenetic clustering of species that belong to different clades but 2 bioRxiv preprint doi: https://doi.org/10.1101/706713; this version posted June 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 37 inhabit southern basins with similar environmental conditions indicated evolutionary 38 convergence. 39 Conclusions 40 Our results support that temperature may be a strong selective pressure driving the 41 evolution of genes involved in the circadian system. By integrating sequence-based 42 functional protein prediction with dN/dS-based methods to detect selection we also 43 uncovered adaptive convergence in the southern populations, probably related to their 44 similar thermal conditions. 45 KEYWORDS 46 adaptation; circadian rhythm; evolutionary convergence; freshwater fish; selection 47 3 bioRxiv preprint doi: https://doi.org/10.1101/706713; this version posted June 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 48 BACKGROUNG 49 Organisms are exposed to daily environmental fluctuations in their natural habitats. 50 To overcome them, organisms developed biological timing systems to optimize their 51 physiological and biochemical processes in space and time [1]. These systems work as 52 internal clocks and require a proper synchronization with environmental signals. Thus, 53 understanding the molecular evolution of the genes involved in the circadian system 54 provide important clues to elucidate how species adapt to their environments. 55 The circadian system is a universal biological timing system found virtually in all 56 organisms [2]. Circadian system is synchronised by light–dark cycle of a day’s period 57 and present oscillations with a period of ~24h called circadian rhythms. Oscillations are 58 generated and regulated at molecular level, but the outcomes have been shown to 59 influence several aspects of physiology, behaviour and ecology of organisms [2, 3]. In 60 fact, circadian rhythms have been shown to improve the inherent ability of several 61 organisms to survive under changing environments, by aiding them to efficiently 62 anticipate periodic events, specifically light changes and climate seasons [2, 3]. 63 The molecular circadian system consists of a network of signalling transduction 64 pathways regulated mainly by interconnected transcription-translation feedback loops 65 (Fig. S1) [4, 5]. The regulatory loops are sustained by the so-called core circadian genes 66 and proteins, requiring about 24h to complete a cycle [1, 5]. In vertebrates, several 67 genes have been reported to be responsible for the maintenance and regulation of the 68 circadian system [1]. The core circadian-genes belong to four main gene families: 69 Cryptochromes (CRY), Period (PER), CLOCK, and BMAL [5]. These gene families 70 encompass several characterized genes (cry, per, bmal and clock) in vertebrates. In fish, 71 several families possess a larger number of circadian paralogs as compared to other 72 vertebrates [6]. For instance, in zebrafish (Danio rerio), several genes have been 4 bioRxiv preprint doi: https://doi.org/10.1101/706713; this version posted June 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 73 identified: six cry (cry1aa, cry1ab, cry1ba, cry1bb, cry2, cry3), four per (per1a, per1b, 74 per2, per3), three bmal (bmal1a, bmal1b, bmal2), and three clock (clocka, clockb, 75 clock2/npas2) [7–10]. Cryptochrome genes encode for a class of flavoproteins that are 76 sensitive to blue light [10], whereas period genes encode for proteins that also display a 77 strong but differential light responsiveness [11, 12]. Both cry and per were found to be 78 key agents in the entrainment of the circadian system, as they constitute the negative 79 elements of the system (i.e. repressors of transcription) [13]. BMAL (Brain and muscle 80 ARNT like) and CLOCK (Circadian locomotor output cycle kaput) families encode for 81 canonical circadian proteins, a highly conserved bHLH (basic-Helix-Loop-Helix)-PAS 82 (Period-Aryl hydrocarbon receptor nuclear translocator- Single minded) transcriptional 83 factors and are the positive elements of the circadian system (i.e. activators of 84 transcription) [1, 5]. 85 Studies in fish allowed to elucidate the different levels of organization of the 86 circadian system. This is because fish are a very diverse group of animals adapted to 87 nearly all aquatic environments and possess a larger number of circadian paralogs as 88 compared to the other vertebrates [6]. Advances in genome sequencing allowed to 89 identify circadian-related genes in several model organisms, including zebrafish. 90 Homology-based methods allowed the identification of circadian genes in other 91 non-model fish species [7–9, 14]. Some studies cover the evolutionary relationships of 92 the core-clock gene families and the mechanisms driving their molecular evolution [7– 93 10, 15], but several key questions remain open, namely the higher number of paralogs 94 in fish when compared to other vertebrates, and its importance for adaptation of species 95 to different environments [6]. 96 5 bioRxiv preprint doi: https://doi.org/10.1101/706713; this version posted June 2, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 97 By sequencing the transcriptome of zebrafish exposed to light, two recent studies 98 identified several genes whose expression depends on light, revealing a multi-level 99 regulation of circadian rhythms by light-cycles [16, 17]. Photoreception is particularly 100 interesting in fish as, contrary to most vertebrates that only perceive light through the 101 eyes, fish also possess a photosensitive pineal gland, dermal melanophores, and brain 102 photoreceptors [1]. In addition, fish possess independent peripheral photoreceptors and 103 self-sustaining circadian oscillators in every tissue [1, 18]. 104 Circadian rhythms can also be entrained by temperature [19–22]. In mammals it 105 was demonstrated that peripheral cells in vitro could sense the change of room 106 temperature as a cue for entrainment of circadian system [19]. In zebrafish, temperature 107 has also an important role in circadian clock [20, 22], and it was proposed that 108 temperature could entrain the phase of the system by driving expression levels of per3, 109 and other circadian genes (namely cry2 and cry1ba) via an alternative hypothetical 110 enhancer [20].
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