Marina Pfalz, Seïf-Eddine Naadja, Jacqui Anne Shykoff, Juergen Kroymann
{"title":"Ectopic Gene Conversion Causing Quantitative Trait Variation.","authors":"Marina Pfalz, Seïf-Eddine Naadja, Jacqui Anne Shykoff, Juergen Kroymann","doi":"10.1093/molbev/msaf086","DOIUrl":"10.1093/molbev/msaf086","url":null,"abstract":"<p><p>Why is there so much non-neutral genetic variation segregating in natural populations? We dissect function and evolution of a near-cryptic quantitative trait locus (QTL) for defense metabolites in Arabidopsis using the CRISPR/Cas9 system and nucleotide polymorphism patterns. The QTL is explained by genetic variation in a family of 4 tightly linked indole-glucosinolate O-methyltransferase genes. Some of this variation appears to be maintained by balancing selection, some appears to be generated by non-reciprocal transfer of sequence, also known as ectopic gene conversion (EGC), between functionally diverged gene copies. Here, we elucidate how EGC, as an inevitable consequence of gene duplication, could be a general mechanism for generating genetic variation for fitness traits.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12042744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nélida Padilla-García, Audrey Le Veve, Vojtěch Čermák, Ömer İltaş, Adrián Contreras-Garrido, Sylvain Legrand, Jean-Marc Aury, Robert Horvath, Clément Lafon Placette
{"title":"The Demographic History of Populations and Genomic Imprinting have Shaped the Transposon Patterns in Arabidopsis lyrata.","authors":"Nélida Padilla-García, Audrey Le Veve, Vojtěch Čermák, Ömer İltaş, Adrián Contreras-Garrido, Sylvain Legrand, Jean-Marc Aury, Robert Horvath, Clément Lafon Placette","doi":"10.1093/molbev/msaf093","DOIUrl":"https://doi.org/10.1093/molbev/msaf093","url":null,"abstract":"<p><p>Purifying selection is expected to prevent the accumulation of transposable elements (TEs) within their host, especially when located in and around genes and if affected by epigenetic silencing. However, positive selection may favor the spread of TEs, causing genomic imprinting under parental conflict, as genomic imprinting allows parent-specific influence over resource accumulation to the progeny. Concomitantly, the number and frequency of TE insertions in natural populations are conditioned by demographic events. In this study, we aimed to test how demography and selective forces interact to affect the accumulation of TEs around genes, depending on their epigenetic silencing, with a particular focus on imprinted genes. To this aim, we compared the frequency and distribution of TEs in Arabidopsis lyrata from Europe and North America. Generally, we found that TE insertions showed a lower frequency when they were inserted in or near genes, especially TEs targeted by epigenetic silencing, suggesting purifying selection at work. We also found that many TEs were lost or got fixed in North American populations during the colonization and the postglacial range expansion from refugia of the species in North America, as well as during the transition to selfing, suggesting a potential \"TE load.\" Finally, we found that silenced TEs increased in frequency and even tended to reach fixation when they were linked to imprinted genes. We conclude that in A. lyrata, genomic imprinting has spread in natural populations through demographic events and positive selection acting on silenced TEs, potentially under a parental conflict scenario.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 5","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How the Structure of Signaling Regulation Evolves: Insights From an Evolutionary Model.","authors":"Danial Asgari, Ann T Tate","doi":"10.1093/molbev/msaf104","DOIUrl":"10.1093/molbev/msaf104","url":null,"abstract":"<p><p>To monitor environmental changes, signaling pathways attenuate their activity with negative feedback loops (NFLs), where proteins produced upon stimulation downregulate the response. NFLs function both upstream of signaling to reduce input and downstream to reduce output. Unlike upstream NFLs, downstream NFLs regulate gene expression without the involvement of intermediate proteins. Thus, we hypothesized that downstream NFLs evolve under more stringent selection than upstream NFLs. Indeed, genes encoding downstream NFLs evolve at a slower and more consistent rate than upstream genes, suggesting that the latter may be under weaker or more context-specific selection. This suggests that downstream NFLs evolve more robustly, whereas upstream NFLs are more susceptible to changes in signaling proteins and stimuli. We tested these assumptions using a minimal model of immune signaling, which predicts robust evolution of downstream NFLs to changes in model parameters. This is consistent with their critical role in regulating signaling and the conservative rate of evolution. Furthermore, we show that the number of signaling steps needed to activate a downstream NFL is influenced by the cost of signaling. Our model predicts that upstream NFLs are more likely to evolve under a shorter half-life of signaling proteins, absence of host-pathogen co-evolution, and a high infection rate. Although it has been proposed that NFLs evolve to reduce the cost of signaling, we show that a high cost does not necessarily predict the evolution of upstream NFLs. The insights from our model have broad implications for understanding the evolution of regulatory mechanisms across signaling pathways.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12093320/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marwa Z Tuffaha, David Castellano, Claudia Serrano Colomé, Ryan N Gutenkunst, Lindi M Wahl
{"title":"Nonhypermutator Cancers Access Driver Mutations Through Reversals in Germline Mutational Bias.","authors":"Marwa Z Tuffaha, David Castellano, Claudia Serrano Colomé, Ryan N Gutenkunst, Lindi M Wahl","doi":"10.1093/molbev/msaf105","DOIUrl":"10.1093/molbev/msaf105","url":null,"abstract":"<p><p>Cancer is an evolutionary disease driven by mutations in asexually reproducing somatic cells. In asexual microbes, bias reversals in the mutation spectrum can speed adaptation by increasing access to previously undersampled beneficial mutations. By analyzing tumors from 20 tissues, along with normal tissue and the germline, we demonstrate this effect in cancer. Nonhypermutated tumors reverse the germline mutation bias and have consistent spectra across tissues. These spectra changes carry the signature of hypoxia, and they facilitate positive selection in cancer genes. Hypermutated and nonhypermutated tumors thus acquire driver mutations differently: hypermutated tumors by higher mutation rates and nonhypermutated tumors by changing the mutation spectrum to reverse the germline mutation bias.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 5","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12104016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144142952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sandipan Paul Arnab, Andre Luiz Campelo Dos Santos, Matteo Fumagalli, Michael DeGiorgio
{"title":"Efficient Detection and Characterization of Targets of Natural Selection Using Transfer Learning.","authors":"Sandipan Paul Arnab, Andre Luiz Campelo Dos Santos, Matteo Fumagalli, Michael DeGiorgio","doi":"10.1093/molbev/msaf094","DOIUrl":"https://doi.org/10.1093/molbev/msaf094","url":null,"abstract":"<p><p>Natural selection leaves detectable patterns of altered spatial diversity within genomes, and identifying affected regions is crucial for understanding species evolution. Recently, machine learning approaches applied to raw population genomic data have been developed to uncover these adaptive signatures. Convolutional neural networks (CNNs) are particularly effective for this task, as they handle large data arrays while maintaining element correlations. However, shallow CNNs may miss complex patterns due to their limited capacity, while deep CNNs can capture these patterns but require extensive data and computational power. Transfer learning addresses these challenges by utilizing a deep CNN pretrained on a large dataset as a feature extraction tool for downstream classification and evolutionary parameter prediction. This approach reduces extensive training data generation requirements and computational needs while maintaining high performance. In this study, we developed TrIdent, a tool that uses transfer learning to enhance detection of adaptive genomic regions from image representations of multilocus variation. We evaluated TrIdent across various genetic, demographic, and adaptive settings, in addition to unphased data and other confounding factors. TrIdent demonstrated improved detection of adaptive regions compared to recent methods using similar data representations. We further explored model interpretability through class activation maps and adapted TrIdent to infer selection parameters for identified adaptive candidates. Using whole-genome haplotype data from European and African populations, TrIdent effectively recapitulated known sweep candidates and identified novel cancer, and other disease-associated genes as potential sweeps.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 5","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Miguel Vasconcelos Almeida, Zixin Li, Pedro Rebelo-Guiomar, Alexandra Dallaire, Lukáš Fiedler, Jonathan L Price, Jan Sluka, Xiaodan Liu, Falk Butter, Christian Rödelsperger, Eric A Miska
{"title":"Transposable Elements Drive Regulatory and Functional Innovation of F-box Genes.","authors":"Miguel Vasconcelos Almeida, Zixin Li, Pedro Rebelo-Guiomar, Alexandra Dallaire, Lukáš Fiedler, Jonathan L Price, Jan Sluka, Xiaodan Liu, Falk Butter, Christian Rödelsperger, Eric A Miska","doi":"10.1093/molbev/msaf097","DOIUrl":"https://doi.org/10.1093/molbev/msaf097","url":null,"abstract":"<p><p>Protein domains of transposable elements (TEs) and viruses increase the protein diversity of host genomes by recombining with other protein domains. By screening 10 million eukaryotic proteins, we identified several domains that define multicopy gene families and frequently co-occur with TE/viral domains. Among these, a Tc1/Mariner transposase helix-turn-helix (HTH) domain was captured by F-box genes in the Caenorhabditis genus, creating a new class of F-box genes. For specific members of this class, like fbxa-215, we found that the HTH domain is required for diverse processes including germ granule localization, fertility, and thermotolerance. Furthermore, we provide evidence that Heat Shock Factor 1 (HSF-1) mediates the transcriptional integration of fbxa-215 into the heat shock response by binding to Helitron TEs directly upstream of the fbxa-215 locus. The interactome of HTH-bearing F-box factors suggests roles in post-translational regulation and proteostasis, consistent with established functions of F-box proteins. Based on AlphaFold2 multimer proteome-wide screens, we propose that the HTH domain may diversify the repertoire of protein substrates that F-box factors regulate post-translationally. We also describe an independent capture of a TE domain by F-box genes in zebrafish. In conclusion, we identify two independent TE domain captures by F-box genes in eukaryotes and provide insights into how these novel proteins are integrated within host gene regulatory networks.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 5","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144013125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giulia Zancolli, Maria Vittoria Modica, Nicolas Puillandre, Yuri Kantor, Agneesh Barua, Giulia Campli, Marc Robinson-Rechavi
{"title":"Redistribution of Ancestral Functions Underlies the Evolution of Venom Production in Marine Predatory Snails.","authors":"Giulia Zancolli, Maria Vittoria Modica, Nicolas Puillandre, Yuri Kantor, Agneesh Barua, Giulia Campli, Marc Robinson-Rechavi","doi":"10.1093/molbev/msaf095","DOIUrl":"10.1093/molbev/msaf095","url":null,"abstract":"<p><p>Venom-secreting glands are highly specialized organs evolved throughout the animal kingdom to synthetize and secrete toxins for predation and defense. Venom is extensively studied for its toxin components and application potential; yet, how animals become venomous remains poorly understood. Venom systems therefore offer a unique opportunity to understand the molecular mechanisms underlying functional innovation. Here, we conducted a multispecies multi-tissue comparative transcriptomics analysis of 12 marine predatory gastropod species, including species with venom glands and species with homologous non-venom-producing glands, to examine how specialized functions evolve through gene expression changes. We found that while the venom gland specialized for the mass production of toxins, its homologous glands retained the ancestral digestive functions. The functional divergence and specialization of the venom gland were achieved through a redistribution of its ancestral digestive functions to other organs, specifically the esophagus. This entailed concerted expression changes and accelerated transcriptome evolution across the entire digestive system. The increase in venom gland secretory capacity was achieved through the modulation of an ancient secretory machinery, particularly genes involved in endoplasmic reticulum stress and unfolded protein response. This study shifts the focus from the well-explored evolution of toxins to the lesser-known evolution of the organ and mechanisms responsible for venom production. As such, it contributes to elucidating the molecular mechanisms underlying organ evolution at a fine evolutionary scale, highlighting the specific events that lead to functional divergence.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 5","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144029901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cassius Manuel, Enes Sakalli, Heiko A Schmidt, Carme Viñas, Arndt von Haeseler, Christiane Elgert
{"title":"When the Past Fades: Detecting Phylogenetic Signal with SatuTe.","authors":"Cassius Manuel, Enes Sakalli, Heiko A Schmidt, Carme Viñas, Arndt von Haeseler, Christiane Elgert","doi":"10.1093/molbev/msaf090","DOIUrl":"10.1093/molbev/msaf090","url":null,"abstract":"<p><p>In phylogenetics, the phenomenon of saturation is well known, although its influence on tree reconstruction lacks a systematic and well-founded method. Here, we propose a new measure of the phylogenetic information shared between two subtrees connected by a branch in a phylogeny. This measure generalizes the concept of saturation between two sequences to a theory of saturation between subtrees, whose implementation we provide as the versatile program SatuTe. We describe different usages of SatuTe, identifying which branches in a tree are phylogenetically informative and which alignment regions support a given branch. As an example, we discuss the Tree of Life reconstruction from ribosomal proteins and the 16S rRNA gene, with emphasis on the two-domain versus three-domain hypotheses. For the branch leading to Eukaryota, we show that most ribosomal proteins contain a strong phylogenetic signal, whereas some regions of the 16S rRNA gene have lost phylogenetic information. Thus, SatuTe opens new insights into phylogenetic inference and complements standard phylogenetic analysis.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 5","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12108095/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Evan S Forsythe, Tony C Gatts, Linnea E Lane, Chris deRoux, Monica J Berggren, Elizabeth A Rehmann, Emily N Zak, Trinity Bartel, Luna A L'Argent, Daniel B Sloan
{"title":"ERCnet: Phylogenomic Prediction of Interaction Networks in the Presence of Gene Duplication.","authors":"Evan S Forsythe, Tony C Gatts, Linnea E Lane, Chris deRoux, Monica J Berggren, Elizabeth A Rehmann, Emily N Zak, Trinity Bartel, Luna A L'Argent, Daniel B Sloan","doi":"10.1093/molbev/msaf089","DOIUrl":"https://doi.org/10.1093/molbev/msaf089","url":null,"abstract":"<p><p>Assigning gene function from genome sequences is a rate-limiting step in molecular biology research. A protein's position within an interaction network can potentially provide insights into its molecular mechanisms. Phylogenetic analysis of evolutionary rate covariation (ERC) in protein sequence has been shown to be effective for large-scale prediction of functional relationships and interactions. However, gene duplication, gene loss, and other sources of phylogenetic incongruence are barriers for analyzing ERC on a genome-wide basis. Here, we developed ERCnet, a bioinformatic program designed to overcome these challenges, facilitating efficient all-versus-all ERC analyses for large protein sequence datasets. We simulated proteome datasets and found that ERCnet achieves combined false positive and negative error rates well below 10% and that our novel \"branch-by-branch\" length measurements outperforms \"root-to-tip\" approaches in most cases, offering a valuable new strategy for performing ERC. We also compiled a sample set of 35 angiosperm genomes to test the performance of ERCnet on empirical data, including its sensitivity to user-defined analysis parameters such as input dataset size and branch-length measurement strategy. We investigated the overlap between ERCnet runs with different species samples to understand how species number and composition affect predicted interactions and to identify the protein sets that consistently exhibit ERC across angiosperms. Our systematic exploration of the performance of ERCnet provides a roadmap for design of future ERC analyses to predict functional interactions in a wide array of genomic datasets. ERCnet code is freely available at https://github.com/EvanForsythe/ERCnet.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 5","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12062884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Akopyan, Anna Tigano, Arne Jacobs, Aryn P Wilder, Nina O Therkildsen
{"title":"Genetic Differentiation is Constrained to Chromosomal Inversions and Putative Centromeres in Locally Adapted Populations With Higher Gene Flow.","authors":"Maria Akopyan, Anna Tigano, Arne Jacobs, Aryn P Wilder, Nina O Therkildsen","doi":"10.1093/molbev/msaf092","DOIUrl":"https://doi.org/10.1093/molbev/msaf092","url":null,"abstract":"<p><p>The impact of genome structure on adaptation is a growing focus in evolutionary biology, revealing an important role for structural variation and recombination landscapes in shaping genetic diversity across genomes and among populations. This is particularly relevant when local adaptation occurs despite gene flow, where clustering of differentiated loci can maintain locally adapted variants by reducing recombination between them. However, the limited genomic resources for nonmodel species, including reference genomes and recombination maps, have constrained our understanding of these patterns. In this study, we leverage the Atlantic silverside-a nonmodel fish with extensive local adaptation across a steep latitudinal gradient-as an ideal system to explore how genome structure influences adaptation under varying levels of gene flow, using a newly available reference genome and multiple recombination maps. Analyzing 168 genomes from four populations, we found a continuum of genome-wide differentiation increasing from south to north, reflecting higher connectivity among southern populations and reduced gene flow at northern latitudes. With increasing gene flow, the number and clustering of FST outlier loci also increased, with differentiated loci found exclusively within large haploblocks harboring inversions and smaller peaks overlapping putative centromeric regions. Notably, sequence divergence was only evident in inversions, supporting their role in adaptive divergence with gene flow, whereas centromeric regions appeared differentiated because of low recombination and diversity, with no indication of elevated divergence. Our results support the hypothesis that clustered genomic architectures evolve with high gene flow and enhance our understanding of how inversions and centromeres are linked to different evolutionary processes.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 5","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046131/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144044402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}