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The European sprat is a small plankton-feeding clupeid present in the northeastern Atlantic Ocean, in the Mediterranean Sea, and in the brackish Baltic Sea and Black Sea. This species is the target of a major fishery and, therefore, an accurate characterization of its genetic population structure is crucial to delineate proper stock assessments that aid ensuring the fishery's sustainability. Here, we present (i) a draft genome assembly, (ii) pooled whole genome sequencing of 19 population samples covering most of the species' distribution range, and (iii) the design and test of a single nucleotide polymorphism (SNP)-chip resource and use this to validate the population structure inferred from pooled sequencing. These approaches revealed, using the populations sampled here, three major groups of European sprat: Oceanic, Coastal, and Brackish with limited differentiation within groups even over wide geographical stretches. Genetic structure is largely driven by six large putative inversions that differentiate Oceanic and Brackish sprats, while Coastal populations display intermediate frequencies of haplotypes at each locus. Interestingly, populations from the Baltic and the Black Seas share similar frequencies of haplotypes at these putative inversions despite their distant geographic location. The closely related clupeids European sprat and Atlantic herring both show genetic adaptation to the brackish Baltic Sea, providing an opportunity to explore the extent of genetic parallelism. This analysis revealed limited parallelism because out of 125 independent loci detected in the Atlantic herring, three showed sharp signals of selection that overlapped between the two species and contained single genes such as PRLRA, which encodes the receptor for prolactin, a freshwater-adapting hormone in euryhaline species, and THRB, a receptor for thyroid hormones, important both for metabolic regulation and the development of red cone photoreceptors.
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Peixes , Polimorfismo de Nucleotídeo Único , Animais , Peixes/genética , Oceano Atlântico , Adaptação Fisiológica/genética , Águas SalinasRESUMO
BACKGROUND: Genome-wide comparisons of populations are widely used to explore the patterns of nucleotide diversity and sequence divergence to provide knowledge on how natural selection and genetic drift affect the genome. In this study we have compared whole-genome sequencing data from Atlantic and Pacific herring, two sister species that diverged about 2 million years ago, to explore the pattern of genetic differentiation between the two species. RESULTS: The genome comparison of the two species revealed high genome-wide differentiation but with islands of remarkably low genetic differentiation, as measured by an FST analysis. However, the low FST observed in these islands is not caused by low interspecies sequence divergence (dxy) but rather by exceptionally high estimated intraspecies nucleotide diversity (π). These regions of low differentiation and elevated nucleotide diversity, termed high-diversity regions in this study, are not enriched for repeats but are highly enriched for immune-related genes. This enrichment includes genes from both the adaptive immune system, such as immunoglobulin, T-cell receptor and major histocompatibility complex genes, as well as a substantial number of genes with a role in the innate immune system, e.g. novel immune-type receptor, tripartite motif and tumor necrosis factor receptor genes. Analysis of long-read based assemblies from two Atlantic herring individuals revealed extensive copy number variation in these genomic regions, indicating that the elevated intraspecies nucleotide diversities were partially due to the cross-mapping of short reads. CONCLUSIONS: This study demonstrates that copy number variation is a characteristic feature of immune trait loci in herring. Another important implication is that these loci are blind spots in classical genome-wide screens for genetic differentiation using short-read data, not only in herring, likely also in other species harboring qualitatively similar variation at immune trait loci. These loci stood out in this study because of the relatively high genome-wide baseline for FST values between Atlantic and Pacific herring.
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Variações do Número de Cópias de DNA , Peixes , Animais , Peixes/genética , Peixes/imunologia , Variação Genética , Oceano Atlântico , Locos de Características Quantitativas , Sequenciamento Completo do GenomaRESUMO
Koalas (Phascolarctos cinereus) have experienced a history of retroviral epidemics leaving their trace as heritable endogenous retroviruses (ERVs) in their genomes. A recently identified ERV lineage, named phaCin-ß, shows a pattern of recent, possibly current, activity with high insertional polymorphism in the population. Here, we investigate geographic patterns of three focal ERV lineages of increasing estimated ages, from the koala retrovirus (KoRV) to phaCin-ß and to phaCin-ß-like, using the whole-genome sequencing of 430 koalas from the Koala Genome Survey. Thousands of ERV loci were found across the population, with contrasting patterns of polymorphism. Northern individuals had thousands of KoRV integrations and hundreds of phaCin-ß ERVs. In contrast, southern individuals had higher phaCin-ß frequencies, possibly reflecting more recent activity and a founder effect. Overall, our findings suggest high ERV burden in koalas, reflecting historic retrovirus-host interactions. Importantly, the ERV catalogue supplies improved markers for conservation genetics in this endangered species.
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Retrovirus Endógenos , Gammaretrovirus , Phascolarctidae , Infecções por Retroviridae , Humanos , Animais , Retrovirus Endógenos/genética , Phascolarctidae/genética , Infecções por Retroviridae/genética , Gammaretrovirus/genética , Sequenciamento Completo do GenomaRESUMO
The transcription factor and cell cycle regulator p53 is marked for degradation by the ubiquitin ligase MDM2. The interaction between these 2 proteins is mediated by a conserved binding motif in the disordered p53 transactivation domain (p53TAD) and the folded SWIB domain in MDM2. The conserved motif in p53TAD from zebrafish displays a 20-fold weaker interaction with MDM2, compared to the interaction in human and chicken. To investigate this apparent difference, we tracked the molecular evolution of the p53TAD/MDM2 interaction among ray-finned fishes (Actinopterygii), the largest vertebrate clade. Intriguingly, phylogenetic analyses, ancestral sequence reconstructions, and binding experiments showed that different loss-of-affinity changes in the canonical binding motif within p53TAD have occurred repeatedly and convergently in different fish lineages, resulting in relatively low extant affinities (KD = 0.5 to 5â µM). However, for 11 different fish p53TAD/MDM2 interactions, nonconserved regions flanking the canonical motif increased the affinity 4- to 73-fold to be on par with the human interaction. Our findings suggest that compensating changes at conserved and nonconserved positions within the motif, as well as in flanking regions of low conservation, underlie a stabilizing selection of "functional affinity" in the p53TAD/MDM2 interaction. Such interplay complicates bioinformatic prediction of binding and calls for experimental validation. Motif-mediated protein-protein interactions involving short binding motifs and folded interaction domains are very common across multicellular life. It is likely that the evolution of affinity in motif-mediated interactions often involves an interplay between specific interactions made by conserved motif residues and nonspecific interactions by nonconserved disordered regions.
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Proteína Supressora de Tumor p53 , Peixe-Zebra , Animais , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Filogenia , Estrutura Terciária de Proteína , Ligação Proteica , Proteínas Proto-Oncogênicas c-mdm2/genética , Proteínas Proto-Oncogênicas c-mdm2/química , Proteínas Proto-Oncogênicas c-mdm2/metabolismoRESUMO
Maintenance of genetic diversity in marine fishes targeted by commercial fishing is a grand challenge for the future. Most of these species are abundant and therefore important for marine ecosystems and food security. Here, we present a road map of how population genomics can promote sustainable fisheries. In these species, the development of reference genomes and whole genome sequencing is key, because genetic differentiation at neutral loci is usually low due to large population sizes and gene flow. First, baseline allele frequencies representing genetically differentiated populations within species must be established. These can then be used to accurately determine the composition of mixed samples, forming the basis for population demographic analysis to inform sustainably set fish quotas. SNP-chip analysis is a cost-effective method for determining baseline allele frequencies and for population identification in mixed samples. Finally, we describe how genetic marker analysis can transform stock identification and management.
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Ecossistema , Pesqueiros , Animais , Metagenômica , Sequenciamento Completo do Genoma/veterináriaRESUMO
Sharks occupy diverse ecological niches and play critical roles in marine ecosystems, often acting as apex predators. They are considered a slow-evolving lineage and have been suggested to exhibit exceptionally low cancer rates. These two features could be explained by a low nuclear mutation rate. Here, we provide a direct estimate of the nuclear mutation rate in the epaulette shark (Hemiscyllium ocellatum). We generate a high-quality reference genome, and resequence the whole genomes of parents and nine offspring to detect de novo mutations. Using stringent criteria, we estimate a mutation rate of 7×10-10 per base pair, per generation. This represents one of the lowest directly estimated mutation rates for any vertebrate clade, indicating that this basal vertebrate group is indeed a slowly evolving lineage whose ability to restore genetic diversity following a sustained population bottleneck may be hampered by a low mutation rate.
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Taxa de Mutação , Tubarões , Animais , Tubarões/genética , EcossistemaRESUMO
Current knowledge of cancer genomics remains biased against noncoding mutations. To systematically search for regulatory noncoding mutations, we assessed mutations in conserved positions in the genome under the assumption that these are more likely to be functional than mutations in positions with low conservation. To this end, we use whole-genome sequencing data from the International Cancer Genome Consortium and combined it with evolutionary constraint inferred from 240 mammals, to identify genes enriched in noncoding constraint mutations (NCCMs), mutations likely to be regulatory in nature. We compare medulloblastoma (MB), which is malignant, to pilocytic astrocytoma (PA), a primarily benign tumor, and find highly different NCCM frequencies between the two, in agreement with the fact that malignant cancers tend to have more mutations. In PA, a high NCCM frequency only affects the BRAF locus, which is the most commonly mutated gene in PA. In contrast, in MB, >500 genes have high levels of NCCMs. Intriguingly, several loci with NCCMs in MB are associated with different ages of onset, such as the HOXB cluster in young MB patients. In adult patients, NCCMs occurred in, e.g., the WASF-2/AHDC1/FGR locus. One of these NCCMs led to increased expression of the SRC kinase FGR and augmented responsiveness of MB cells to dasatinib, a SRC kinase inhibitor. Our analysis thus points to different molecular pathways in different patient groups. These newly identified putative candidate driver mutations may aid in patient stratification in MB and could be valuable for future selection of personalized treatment options.
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Neoplasias Cerebelares , Meduloblastoma , Adulto , Animais , Humanos , Meduloblastoma/patologia , Mutação , Genoma , Neoplasias Cerebelares/genética , Quinases da Família src/genética , Mamíferos/genética , Proteínas de Ligação a DNA/genéticaRESUMO
Understanding how populations adapt to their environment is increasingly important to prevent biodiversity loss due to overexploitation and climate change. Here we studied the population structure and genetic basis of local adaptation of Atlantic horse mackerel, a commercially and ecologically important marine fish that has one of the widest distributions in the eastern Atlantic. We analyzed whole-genome sequencing and environmental data of samples collected from the North Sea to North Africa and the western Mediterranean Sea. Our genomic approach indicated low population structure with a major split between the Mediterranean Sea and the Atlantic Ocean and between locations north and south of mid-Portugal. Populations from the North Sea are the most genetically distinct in the Atlantic. We discovered that most population structure patterns are driven by a few highly differentiated putatively adaptive loci. Seven loci discriminate the North Sea, two the Mediterranean Sea, and a large putative inversion (9.9 Mb) on chromosome 21 underlines the north-south divide and distinguishes North Africa. A genome-environment association analysis indicates that mean seawater temperature and temperature range, or factors correlated to them, are likely the main environmental drivers of local adaptation. Our genomic data broadly support the current stock divisions, but highlight areas of potential mixing, which require further investigation. Moreover, we demonstrate that as few as 17 highly informative SNPs can genetically discriminate the North Sea and North African samples from neighboring populations. Our study highlights the importance of both, life history and climate-related selective pressures in shaping population structure patterns in marine fish. It also supports that chromosomal rearrangements play a key role in local adaptation with gene flow. This study provides the basis for more accurate delineation of the horse mackerel stocks and paves the way for improving stock assessments.
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Atlantic herring (Clupea harengus) and Pacific herring (C. pallasii) are sister species that split from a common ancestor about 2 million years ago. Balsfjord, a subarctic fjord in Northern Norway, harbors an outpost population of Pacific herring within the range of the Atlantic herring. We used whole genome sequencing to show that gene flow from Atlantic herring into the Balsfjord population has generated a stable hybrid population that has persisted for thousands of generations. The Atlantic herring ancestry in Balsfjord was estimated in the range 25-26%. The old age and large proportion of introgressed regions suggest there are no obvious genetic incompatibilities between species. Introgressed regions were widespread in the genome and large, with some in excess of 1 Mb, and they were overrepresented in low-recombination regions. We show that the distribution of introgressed material is non-random; introgressed sequence blocks in different individuals are shared more often than expected by chance. Furthermore, introgressed regions tend to show elevated divergence (FST) between Atlantic and Pacific herring. Together, our results suggest that introgression of genetic material has facilitated adaptation in the Balsfjord population. The Balsfjord population provides a rare example of a stable interspecies hybrid population that has persisted over thousands of years.
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Estuários , Peixes , Humanos , Animais , Peixes/genética , Dinâmica Populacional , Noruega , GenomaRESUMO
Endogenous retroviruses (ERVs) are inherited remnants of retroviruses that colonized host germline over millions of years, providing a sampling of retroviral diversity across time. Here, we utilize the strength of Darwin's finches, a system synonymous with evolutionary studies, for investigating ERV history, revealing recent retrovirus-host interactions in natural populations. By mapping ERV variation across all species of Darwin's finches and comparing with outgroup species, we highlight geographical and historical patterns of retrovirus-host occurrence, utilizing the system for evaluating the extent and timing of retroviral activity in hosts undergoing adaptive radiation and colonization of new environments. We find shared ERVs among all samples indicating retrovirus-host associations pre-dating host speciation, as well as considerable ERV variation across populations of the entire Darwin's finches' radiation. Unexpected ERV variation in finch species on different islands suggests historical changes in gene flow and selection. Non-random distribution of ERVs along and between chromosomes, and across finch species, suggests association between ERV accumulation and the rapid speciation of Darwin's finches.
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Retrovirus Endógenos , Tentilhões , Passeriformes , Animais , Evolução Biológica , Equador , Retrovirus Endógenos/genética , Tentilhões/genética , Fluxo Gênico , Passeriformes/genética , FilogeniaRESUMO
Atlantic herring in International Council for Exploration of the Sea (ICES) Divisions 6.a, 7.b-c comprises at least three populations, distinguished by temporal and spatial differences in spawning, which have until recently been managed as two stocks defined by geographical delineators. Outside of spawning the populations form mixed aggregations, which are the subject of acoustic surveys. The inability to distinguish the populations has prevented the development of separate survey indices and separate stock assessments. A panel of 45 single-nucleotide polymorphisms, derived from whole-genome sequencing, were used to genotype 3480 baseline spawning samples (2014-2021). A temporally stable baseline comprising 2316 herring from populations known to inhabit Division 6.a was used to develop a genetic assignment method, with a self-assignment accuracy greater than 90%. The long-term temporal stability of the assignment model was validated by assigning archive (2003-2004) baseline samples (270 individuals) with a high level of accuracy. Assignment of non-baseline samples (1514 individuals) from Divisions 6.a, 7.b-c indicated previously unrecognized levels of mixing of populations outside of the spawning season. The genetic markers and assignment models presented constitute a 'toolbox' that can be used for the assignment of herring caught in mixed survey and commercial catches in Division 6.a into their population of origin with a high level of accuracy.
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Time-domain backprojection algorithms are widely used in state-of-the-art synthetic aperture radar (SAR) imaging systems that are designed for applications where motion error compensation is required. These algorithms include an interpolation procedure, under which an unknown SAR range-compressed data parameter is estimated based on complex-valued SAR data samples and backprojected into a defined image plane. However, the phase of complex-valued SAR parameters estimated based on existing interpolators does not contain correct information about the range distance between the SAR imaging system and the given point of space in a defined image plane, which affects the quality of reconstructed SAR scenes. Thus, a phase-control procedure is required. This paper introduces extensions of existing linear, cubic, and sinc interpolation algorithms to interpolate complex-valued SAR data, where the phase of the interpolated SAR data value is controlled through the assigned a priori known range time that is needed for a signal to reach the given point of the defined image plane and return back. The efficiency of the extended algorithms is tested at the Nyquist rate on simulated and real data at THz frequencies and compared with existing algorithms. In comparison to the widely used nearest-neighbor interpolation algorithm, the proposed extended algorithms are beneficial from the lower computational complexity perspective, which is directly related to the offering of smaller memory requirements for SAR image reconstruction at THz frequencies.
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Recent adaptive radiations are models for investigating mechanisms contributing to the evolution of biodiversity. An unresolved question is the relative importance of new mutations, ancestral variants, and introgressive hybridization for phenotypic evolution and speciation. Here, we address this issue using Darwin's finches and investigate the genomic architecture underlying their phenotypic diversity. Admixture mapping for beak and body size in the small, medium, and large ground finches revealed 28 loci showing strong genetic differentiation. These loci represent ancestral haplotype blocks with origins predating speciation events during the Darwin's finch radiation. Genes expressed in the developing beak are overrepresented in these genomic regions. Ancestral haplotypes constitute genetic modules for selection and act as key determinants of the unusual phenotypic diversity of Darwin's finches. Such ancestral haplotype blocks can be critical for how species adapt to environmental variability and change.
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Tentilhões , Passeriformes , Animais , Bico , Tentilhões/genética , Genômica , HaplótiposRESUMO
Retroviruses have left their legacy in host genomes over millions of years as endogenous retroviruses (ERVs), and their structure, diversity, and prevalence provide insights into the historical dynamics of retrovirus-host interactions. In bioinformatic analyses of koala (Phascolarctos cinereus) whole-genome sequences, we identify a recently expanded ERV lineage (phaCin-ß) that is related to the New World squirrel monkey retrovirus. This ERV expansion shares many parallels with the ongoing koala retrovirus (KoRV) invasion of the koala genome, including highly similar and mostly intact sequences, and polymorphic ERV loci in the sampled koala population. The recent phaCin-ß ERV colonization of the koala genome appears to predate the current KoRV invasion, but polymorphic ERVs and divergence comparisons between these two lineages predict a currently uncharacterized, possibly still extant, phaCin-ß retrovirus. The genomics approach to ERV-guided discovery of novel retroviruses in host species provides a strong incentive to search for phaCin-ß retroviruses in the Australasian fauna.
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Betaretrovirus , Retrovirus Endógenos , Interações entre Hospedeiro e Microrganismos , Phascolarctidae , Infecções por Retroviridae , Animais , Betaretrovirus/genética , Retrovirus Endógenos/genética , Evolução Molecular , Genoma , Genômica , Phascolarctidae/genética , Phascolarctidae/virologia , Infecções por Retroviridae/veterinária , Infecções por Retroviridae/virologiaRESUMO
This article proposes an Automatic Target Recognition (ATR) algorithm to classify non-cooperative targets in Synthetic Aperture Radar (SAR) images. The scarcity or nonexistence of measured SAR data demands that classification algorithms rely only on synthetic data for training purposes. Based on a model represented by the set of scattering centers extracted from purely synthetic data, the proposed algorithm generates hypotheses for the set of scattering centers extracted from the target under test belonging to each class. A Goodness of Fit test is considered to verify each hypothesis, where the Likelihood Ratio Test is modified by a scattering center-weighting function common to both the model and target. Some algorithm variations are assessed for scattering center extraction and hypothesis generation and verification. The proposed solution is the first model-based classification algorithm to address the recently released Synthetic and Measured Paired Labeled Experiment (SAMPLE) dataset on a 100% synthetic training data basis. As a result, an accuracy of 91.30% in a 10-target test within a class experiment under Standard Operating Conditions (SOCs) was obtained. The algorithm was also pioneered in testing the SAMPLE dataset in Extend Operating Conditions (EOCs), assuming noise contamination and different target configurations. The proposed algorithm was shown to be robust for SNRs greater than -5 dB.
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Reconhecimento Automatizado de Padrão , Radar , Algoritmos , Reconhecimento PsicológicoRESUMO
[This corrects the article DOI: 10.1371/journal.pgen.1009726.].
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Selective breeding for desirable traits in strictly controlled populations has generated an extraordinary diversity in canine morphology and behaviour, but has also led to loss of genetic variation and random entrapment of disease alleles. As a consequence, specific diseases are now prevalent in certain breeds, but whether the recent breeding practice led to an overall increase in genetic load remains unclear. Here we generate whole genome sequencing (WGS) data from 20 dogs per breed from eight breeds and document a ~10% rise in the number of derived alleles per genome at evolutionarily conserved sites in the heavily bottlenecked cavalier King Charles spaniel breed (cKCs) relative to in most breeds studied here. Our finding represents the first clear indication of a relative increase in levels of deleterious genetic variation in a specific breed, arguing that recent breeding practices probably were associated with an accumulation of genetic load in dogs. We then use the WGS data to identify candidate risk alleles for the most common cause for veterinary care in cKCs-the heart disease myxomatous mitral valve disease (MMVD). We verify a potential link to MMVD for candidate variants near the heart specific NEBL gene in a dachshund population and show that two of the NEBL candidate variants have regulatory potential in heart-derived cell lines and are associated with reduced NEBL isoform nebulette expression in papillary muscle (but not in mitral valve, nor in left ventricular wall). Alleles linked to reduced nebulette expression may hence predispose cKCs and other breeds to MMVD via loss of papillary muscle integrity.
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Doenças do Cão/genética , Cães/genética , Variação Genética , Doenças das Valvas Cardíacas/veterinária , Valva Mitral/patologia , Mutação , Alelos , Animais , Ensaio de Desvio de Mobilidade Eletroforética , Expressão Gênica , Doenças das Valvas Cardíacas/genéticaRESUMO
OBJECTIVES: To further elucidate the role of the MHC in ankylosing spondylitis by typing 17 genes, searching for HLA-B∗27 independent associations and assessing the impact of sex on this male biased disease. METHODS: High-confidence two-field resolution genotyping was performed on 310 cases and 2196 controls using an n-1 concordance method. Protein-coding variants were called from next-generation sequencing reads using up to four software programs and the consensus result recorded. Logistic regression tests were applied to the dataset as a whole, and also in stratified sets based on sex or HLA-B∗27 status. The amino acids driving association were also examined. RESULTS: Twenty-five HLA protein-coding variants were significantly associated to disease in the population. Three novel protective associations were found in a HLA-B∗27 positive population, HLA-A∗24:02 (OR = 0.4, CI = 0.2-0.7), and HLA-A amino acids Leu95 and Gln156. We identified a key set of seven loci that were common to both sexes, and robust to change in sample size. Stratifying by sex uncovered three novel risk variants restricted to the female population (HLA-DQA1∗04.01, -DQB1∗04:02, -DRB1∗08:01; OR = 2.4-3.1). We also uncovered a set of neutral variants in the female population, which in turn conferred strong effects in the male set, highlighting how population composition can lead to the masking of true associations. CONCLUSION: Population stratification allowed for a nuanced investigation into the tightly linked MHC region, revealing novel HLA-B∗27 signals as well as replicating previous HLA-B∗27 dependent results. This dissection of signals may help to elucidate sex biased disease predisposition and clinical progression.
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The underlying molecular mechanisms that determine long day versus short day breeders remain unknown in any organism. Atlantic herring provides a unique opportunity to examine the molecular mechanisms involved in reproduction timing, because both spring and autumn spawners exist within the same species. Although our previous whole genome comparisons revealed a strong association of TSHR alleles with spawning seasons, the functional consequences of these variants remain unknown. Here we examined the functional significance of six candidate TSHR mutations strongly associated with herring reproductive seasonality. We show that the L471M missense mutation in the spring-allele causes enhanced cAMP signaling. The best candidate non-coding mutation is a 5.2 kb retrotransposon insertion upstream of the TSHR transcription start site, near an open chromatin region, which is likely to affect TSHR expression. The insertion occurred prior to the split between Pacific and Atlantic herring and was lost in the autumn-allele. Our study shows that strongly associated coding and non-coding variants at the TSHR locus may both contribute to the regulation of seasonal reproduction in herring.
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Peixes/fisiologia , Receptores da Tireotropina/genética , Alelos , Animais , Oceano Atlântico , Sequência Conservada , Haplótipos , Mutação , Receptores da Tireotropina/fisiologia , Reprodução/fisiologia , Estações do Ano , Transdução de Sinais , Tireotropina Subunidade beta/genéticaRESUMO
Retroviruses have infiltrated vertebrate germlines for millions of years as inherited endogenous retroviruses (ERVs). Mammalian genomes host large numbers of ERVs and transposable elements (TEs), including retrotransposons and DNA transposons, that contribute to genomic innovation and evolution as coopted genes and regulators of diverse functions. To explore features distinguishing coopted ERVs and TEs from other integrations, we focus on the potential role of ZBED6 and repeated ERV domestication as repurposed Syncytin genes. The placental mammal-specific ZBED6 is a DNA transposon-derived transcription regulator and we demonstrate that its binding motifs are associated with distinct Syncytins and that ZBED6 binding motifs are 2- to 3-fold more frequent in ERVs than in flanking DNA. Our observations suggest that ZBED6 could contribute an extended regulatory role of genomic expression, utilizing ERVs as platforms for genomic innovation and evolution.