Journal of Molecular Evolution最新文献

Stochastic Character Mapping: An Under-Exploited Approach to the Study of Molecular Evolution. 随机特征映射：一种未被充分利用的分子进化研究方法。

IF 2.1 3区生物学

Journal of Molecular Evolution Pub Date : 2025-07-08 DOI: 10.1007/s00239-025-10257-5

Simon Laurin-Lemay, Nicolas Rodrigue

引用次数: 0

Possible Acquisition and Molecular Evolution of vpu Genes Inferred from Comprehensive Sequence Analysis of Human and Simian Immunodeficiency Viruses. 从人类和猿猴免疫缺陷病毒的综合序列分析推断vpu基因的可能获取和分子进化。

IF 2.1 3区生物学

Journal of Molecular Evolution Pub Date : 2025-06-21 DOI: 10.1007/s00239-025-10256-6

Miu Naruki, Motofumi Saito, Masako Nomaguchi, Akio Kanai

{"title":"Possible Acquisition and Molecular Evolution of vpu Genes Inferred from Comprehensive Sequence Analysis of Human and Simian Immunodeficiency Viruses.","authors":"Miu Naruki, Motofumi Saito, Masako Nomaguchi, Akio Kanai","doi":"10.1007/s00239-025-10256-6","DOIUrl":"10.1007/s00239-025-10256-6","url":null,"abstract":"Vpu, an accessory protein of human immunodeficiency virus-1 (HIV-1), plays a crucial role in viral particle production and significantly contributes to HIV virulence. However, the evolution of the vpu gene remains poorly understood. We conducted a computational analysis of approximately 39,000 simian immunodeficiency virus (SIV) and HIV sequences, focusing on 141 representative Vpu proteins. Phylogenetic analysis classified the SIV and HIV strains into four major types based on their Vpu proteins: Vpu-type 1 (ancestral, found in SIVs such as SIVmon and SIVgsn), Vpu-type 2 (SIVgor and HIV-1 group O), Vpu-type 3 (SIVcpz), and Vpu-type 4 (HIV-1 group M and N). Notably, Vpu-type 1 exhibited variability in gene length, genome length, and the overlap between vpu and env compared with other Vpu-types. A phylogenetic tree was constructed using 426 nucleotide sequences from HIV-1, HIV-2, and SIVs focusing on the region between the pol and env genes. Vpu-type 1 was closely clustered with SIVasc and SIVsyk, lacking both vpu and vpx. The similarities observed between vpu and genes such as vpr and env suggest that vpu originated within the SIV genome. In addition, a phylogenetic tree constructed from 252 Vpu-type 4a sequences from the HIV pandemic strain and 135 sequences of circulating recombinant forms of HIV-1 revealed 18 distinct protein subtypes, exceeding the number of previously recognized subtypes. The systematic analysis of the sequences from large datasets has enabled a detailed characterization of the transition states of vpu, enhancing our understanding of the processes driving viral diversity.","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":""},"PeriodicalIF":2.1,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Convergent Evolution of Two Dopamine Receptor Genes: Repeated Evolution of Exon 6 Skipping in Drd2, and Repeated Deletion of Exon 6 in Drd3. 两种多巴胺受体基因的趋同进化：Drd2外显子6跳跃的重复进化和Drd3外显子6的重复缺失。

IF 2.1 3区生物学

Journal of Molecular Evolution Pub Date : 2025-06-01 Epub Date: 2025-06-09 DOI: 10.1007/s00239-025-10255-7

Michael T Peglar, Karl J Fryxell

{"title":"Convergent Evolution of Two Dopamine Receptor Genes: Repeated Evolution of Exon 6 Skipping in Drd2, and Repeated Deletion of Exon 6 in Drd3.","authors":"Michael T Peglar, Karl J Fryxell","doi":"10.1007/s00239-025-10255-7","DOIUrl":"10.1007/s00239-025-10255-7","url":null,"abstract":"Drd2 dopamine receptor mRNAs are alternatively spliced in rodents and primates by skipping exon 6 to produce the D2S protein, or including exon 6 to produce the D2L protein. These protein isoforms have differing roles in pre- vs. post-synaptic signaling, cytoplasmic vesicle processing, and calcium-mediated desensitization. Genetic alteration in the D2S/D2L ratio affects human behavior and cognition at multiple levels, including working memory. Here we show that exon 6 originated early in vertebrate evolution, after the duplication and divergence of D2 and D4 dopamine receptor genes, but before the duplication and divergence of D2 and D3 dopamine receptor genes. Exon 6 encodes a relatively conserved sequence in the third cytoplasmic loop of the D2-D3 receptor. Its amino acid sequence is relatively short (24-33 amino acids), and is not strictly necessary for dopamine signal transduction. Exon skipping of Drd2 exon 6 was not detectable in the brains of cyclostomes, sharks, fish, relatively primitive amphibians (Xenopus, Notophthalmus), relatively primitive reptiles (turtles), relatively primitive birds (ostrich), or relatively primitive mammals (monotremes and marsupials). However, exon skipping of Drd2 exon 6 did occur at significant levels in the brains of more derived amphibians, reptiles, birds and mammals. Thus, skipping of Drd2 exon 6 arose convergently and specifically in the more derived tetrapod lineages, none of which deleted this exon. In contrast, exon 6 was convergently deleted during Drd3 evolution in an apparently random subset of the species of sharks, fish, amphibians, reptiles, birds, and mammals.","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"441-464"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adaptation to Freshwater in Allis Shad Involved a Combination of Genomic and Epigenomic Changes. 沙尾鱼对淡水的适应涉及基因组和表观基因组变化的结合。

IF 2.1 3区生物学

Journal of Molecular Evolution Pub Date : 2025-06-01 Epub Date: 2025-06-02 DOI: 10.1007/s00239-025-10253-9

Paulo Pereira, Sandra Afonso, António Múrias, Miguel Carneiro, Stephen J Sabatino

{"title":"Adaptation to Freshwater in Allis Shad Involved a Combination of Genomic and Epigenomic Changes.","authors":"Paulo Pereira, Sandra Afonso, António Múrias, Miguel Carneiro, Stephen J Sabatino","doi":"10.1007/s00239-025-10253-9","DOIUrl":"10.1007/s00239-025-10253-9","url":null,"abstract":"Epigenetic modifications are one of the evolutionary mechanisms that allow individuals and populations to adapt to environmental changes. However, the relative importance of epigenetic versus genetic changes in adaptation and how they may interact remains poorly understood. Here, we investigate the role of DNA methylation in adaptation by studying a population of Allis shad (Alosa alosa) that evolved a completely freshwater life history approximately 70 years ago and the anadromous one that founded it. Using reduced representation bisulfite sequencing, we identified 227 differentially methylated regions (DMRs) between them, overlapping known important genes for freshwater adaptation, such as ATP2B4, PRLH2, and KCNF1A. Enrichment analysis of GO terms suggested that genes in the identified DMRs play key roles in neural, growth, and developmental functions, which is concordant with previous studies on adaptation to freshwater in this species and genus. Using pool-seq data from an earlier study, we then tested if the DMRs for freshwater shad found here overlapped genomic outlier regions that may be under genetic selection in three independently evolved, freshwater populations (including the one studied here). Our analysis showed that the DMRs identified here fall broadly outside genomic regions under natural selection. However, 45% of these were associated with CpG > TpG deamination events in DMRs, a mutation tightly linked with DNA methylation. Our study illustrates that both genetic and epigenetic mechanisms are important during the initial stages of adaptation in this system. It also supports the hypothesis that methylation may generate polymorphism that fuels adaptive evolution.","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"406-422"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198289/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Abundance of Viroid-Like RNA Obelisk-S.s in Streptococcus sanguinis SK36 May Suffice for Evolutionary Persistence. 类病毒RNA丰度的研究。血链球菌SK36可能足以维持进化持久性。

IF 2.1 3区生物学

Journal of Molecular Evolution Pub Date : 2025-06-01 Epub Date: 2025-05-09 DOI: 10.1007/s00239-025-10250-y

Rohan Maddamsetti, Lingchong You

{"title":"The Abundance of Viroid-Like RNA Obelisk-S.s in Streptococcus sanguinis SK36 May Suffice for Evolutionary Persistence.","authors":"Rohan Maddamsetti, Lingchong You","doi":"10.1007/s00239-025-10250-y","DOIUrl":"10.1007/s00239-025-10250-y","url":null,"abstract":"A new class of viroid-like RNAs, called Obelisks, was recently reported by Zheludev et al. (Cell 187:6521-6536.e6518, 2024). They found thousands of Obelisk sequences globally and identified a specific 1137 nt Obelisk, called Obelisk-S.s, in monoculture transcriptomes of Streptococcus sanguinis SK36, a commensal bacterium of the human oral microbiome. Here, we confirm that Obelisk-S.s is highly abundant in SK36, despite its absence from the SK36 genome (i.e., as DNA). In 11 out of 17 monoculture SK36 RNA-seq datasets examined, Obelisk-S.s is more abundant than any mRNA. Given its relative abundance, we hypothesized that multiple Obelisk-S.s variants could coexist within SK36. We found three Obelisk-S.s mutations at 5-10% allele frequency in some samples: a R162R synonymous mutation in one set of replicate transcriptomes, and an I48I synonymous mutation and an intergenic mutation in another set of replicate transcriptomes. A simple mathematical model shows how high Obelisk abundance can transiently stabilize intracellular Obelisk populations, and how extreme Obelisk abundances may stabilize intracellular Obelisk populations indefinitely. Evolution experiments with SK36 could test this theory and could shed light on how Obelisks function and evolve within their microbial hosts.","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"370-378"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ancient Host-Virus Gene Transfer Hints at a Diverse Pre-LECA Virosphere. 古代宿主-病毒基因转移暗示了多样化的前leca病毒圈。

IF 2.1 3区生物学

Journal of Molecular Evolution Pub Date : 2025-06-01 Epub Date: 2025-04-29 DOI: 10.1007/s00239-025-10246-8

Sangita Karki, Zachary K Barth, Frank O Aylward

{"title":"Ancient Host-Virus Gene Transfer Hints at a Diverse Pre-LECA Virosphere.","authors":"Sangita Karki, Zachary K Barth, Frank O Aylward","doi":"10.1007/s00239-025-10246-8","DOIUrl":"10.1007/s00239-025-10246-8","url":null,"abstract":"The details surrounding the early evolution of eukaryotes and their viruses are largely unknown. Several key enzymes involved in DNA synthesis and transcription are shared between eukaryotes and large DNA viruses in the phylum Nucleocytoviricota, but the evolutionary relationships between these genes remain unclear. In particular, previous studies of eukaryotic DNA and RNA polymerases often show deep-branching clades of eukaryotes and viruses indicative of ancient gene exchange. Here, we performed updated phylogenetic analysis of eukaryotic and viral family B DNA polymerases, multimeric RNA polymerases, and mRNA-capping enzymes to explore their evolutionary relationships. Our results show that viral enzymes form clades that are typically adjacent to eukaryotes, suggesting that they originate prior to the emergence of the Last Eukaryotic Common Ancestor (LECA). The machinery for viral DNA replication, transcription, and mRNA capping are all key processes needed for the maintenance of virus factories, which are complex structures formed by many nucleocytoviruses during infection, indicating that viruses capable of making these structures are ancient. These findings hint at a diverse and complex pre-LECA virosphere and indicate that large DNA viruses may encode proteins that are relics of extinct proto-eukaryotic lineages.","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"295-305"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144015739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Caspase Domain Duplication During the Evolution of Caspase-16. Caspase-16进化过程中的Caspase结构域复制。

IF 2.1 3区生物学

Journal of Molecular Evolution Pub Date : 2025-06-01 Epub Date: 2025-05-20 DOI: 10.1007/s00239-025-10252-w

Leopold Eckhart, Attila Placido Sachslehner, Julia Steinbinder, Heinz Fischer

{"title":"Caspase Domain Duplication During the Evolution of Caspase-16.","authors":"Leopold Eckhart, Attila Placido Sachslehner, Julia Steinbinder, Heinz Fischer","doi":"10.1007/s00239-025-10252-w","DOIUrl":"10.1007/s00239-025-10252-w","url":null,"abstract":"Caspases are cysteine-dependent aspartate-directed proteases which have critical functions in programmed cell death and inflammation. Their catalytic activity depends on a catalytic dyad of cysteine and histidine within a characteristic protein fold, the so-called caspase domain. Here, we investigated the evolution of caspase-16 (CASP16), an enigmatic member of the caspase family, for which only a partial human gene had been reported previously. The presence of CASP16 orthologs in placental mammals, marsupials and monotremes suggests that caspase-16 originated prior to the divergence of the main phylogenetic clades of mammals. Caspase-16 proteins of various species contain a carboxy-terminal caspase domain and an amino-terminal prodomain predicted to fold into a caspase domain-like structure, which is a unique feature among caspases known so far. Comparative sequence analysis indicates that the prodomain of caspase-16 has evolved by the duplication of exons encoding the caspase domain, whereby the catalytic site was lost in the amino-terminal domain and conserved in the carboxy-terminal domain of caspase-16. The murine and human orthologs of CASP16 contain frameshift mutations and therefore represent pseudogenes (CASP16P). CASP16 of the chimpanzee displays more than 98% nucleotide sequence identity with the human CASP16P gene but, like CASP16 genes of other primates, has an intact protein coding sequence. We conclude that caspase-16 structurally differs from other mammalian caspases, and the pseudogenization of CASP16 distinguishes humans from their phylogenetically closest relatives.","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"395-405"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Refined Phylogenetic Ortholog Inference Reveals Coevolutionary Expansion of the MAPK Signaling Network Through Finetuning of Pathway Specificity. 精细化的系统发育同源推断揭示了MAPK信号网络通过通路特异性微调的共同进化扩展。

IF 2.1 3区生物学

Journal of Molecular Evolution Pub Date : 2025-06-01 Epub Date: 2025-05-30 DOI: 10.1007/s00239-025-10254-8

E J Huang, Jeeun Parksong, Amy F Peterson, Fernando Torres, Sergi Regot, Gabriel S Bever

{"title":"Refined Phylogenetic Ortholog Inference Reveals Coevolutionary Expansion of the MAPK Signaling Network Through Finetuning of Pathway Specificity.","authors":"E J Huang, Jeeun Parksong, Amy F Peterson, Fernando Torres, Sergi Regot, Gabriel S Bever","doi":"10.1007/s00239-025-10254-8","DOIUrl":"10.1007/s00239-025-10254-8","url":null,"abstract":"The evolutionary origins of the three-tier mitogen-activated protein kinase (MAPK) signaling network remain poorly understood despite its indispensable role in eukaryote physiology. Here, we develop a novel two-step method combining relaxed ortholog candidate search with iterative phylogenetic evaluation to identify orthologs across critical eukaryotic lineages. We perform a comprehensive phylogenetic analysis to delineate the history of divergence for non-human orthologs of human paralogs along the human evolutionary backbone. Our detailed evolutionary trees of MAPKs, MAP2Ks, and MAP3Ks reveal two major pulses of coevolutionary tandem expansion: one predating the divergence of fungi and animals, and the other predating the origin of animals. Our reconstruction also infers a polyphyletic origin for the atypical MAPKs. Integrating functional literature across eukaryotic taxa with our trees reveals that the two clades of MAP3K, Sterile-like (STE) and tyrosine kinase-like (TKL), had distinct trajectories and influences on downstream pathway diversification. STEs that function as MAP3Ks are conserved across extant eukaryotes. While TKL MAP3Ks are absent in many early diverging eukaryotes, their expansion aligns phylogenetically and functionally with that of downstream MAP2Ks and MAPKs. We propose that the MAPK network originated as a STE MAP3K-regulated pathway, but subsequent recruitment and radiations of TKL MAP3Ks drove downstream diversification in parallel, manifesting in top-down finetuning of pathway specificity. Our study provides an evolutionary framework for the functional diversity of this complex signaling network, demonstrating that phylogenetic insights can generate new hypotheses to understand fundamental cellular processes.","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"423-440"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genomic AT Bias Coupled with Amino Acid Metabolism Modulates Codon Usage. 基因组AT偏差与氨基酸代谢耦合调节密码子使用。

IF 2.1 3区生物学

Journal of Molecular Evolution Pub Date : 2025-06-01 Epub Date: 2025-05-20 DOI: 10.1007/s00239-025-10251-x

Lucio Aliperti Car, Ignacio E Sánchez

{"title":"Genomic AT Bias Coupled with Amino Acid Metabolism Modulates Codon Usage.","authors":"Lucio Aliperti Car, Ignacio E Sánchez","doi":"10.1007/s00239-025-10251-x","DOIUrl":"10.1007/s00239-025-10251-x","url":null,"abstract":"Encoding of protein-coding sequences in a genome through evolution leads to characteristic proportions of codons and amino acids. Here, we present a simplified maximum entropy model that groups together codons with the same GC (guanine + cytosine) content and coding for the same amino acid and accounts for the stoichiometry of genetic elements in over 50000 genomes with seven interpretable parameters. Our model includes both the cost of a codon given a genomic GC content and the metabolic cost of the corresponding amino acid. Both costs are essential for accurate prediction of codon and amino acid abundances. The best implementation of the model includes a universal equilibrium value for the genomic GC content below 50%, as suggested by the literature. It also splits the twenty amino acids in two groups forming strong (bases C and G) or weak (bases A and U) Watson Crick base pairs with the anticodon, differing in the strength of GC-dependent selection. The entropy-cost trade-off suggests that each organism has sorted out the genome encoding problem given a value for its genomic GC content. The empirical boundaries to this trade-off suggest minimal values for the amino acid and codon entropies, which may limit the GC content of natural genomes.","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"379-394"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolutionary and Structural Assessment of the Human Secreted Frizzled-Related Protein (SFRP) Family. 人类分泌卷曲相关蛋白（SFRP）家族的进化和结构评估。

IF 2.1 3区生物学

Journal of Molecular Evolution Pub Date : 2025-06-01 Epub Date: 2025-05-15 DOI: 10.1007/s00239-025-10249-5

Ladan Mafakher, Elham Rismani, Ladan Teimoori-Toolabi

{"title":"Evolutionary and Structural Assessment of the Human Secreted Frizzled-Related Protein (SFRP) Family.","authors":"Ladan Mafakher, Elham Rismani, Ladan Teimoori-Toolabi","doi":"10.1007/s00239-025-10249-5","DOIUrl":"10.1007/s00239-025-10249-5","url":null,"abstract":"It has been observed that five members of Secreted Frizzled-Related proteins act as antagonists for the Wnt signaling pathway in humans. These glycoproteins have two functional domains: the cysteine-rich domain (CRD) and the netrin-related domain (NTR), with a completely conserved disulfide bond in the CRD domain. Phylogenetic analysis revealed that this protein family can be divided into two subgroups, SFRP1/SFRP2/SFRP5 versus SFRP3/SFRP4. The SFRP3/SFRP4 group was found to be more closely related to the sponge Lubomirskia baicalensis, which is believed to represent the ancient origin of SFRPs. The model evaluation demonstrated high-quality conformational homology modeling in the predicted Human SFRP models compared to the Sizzled crystal structure of Xenopus laevis. The molecular dynamic simulation illustrated that SFRP1 and SFRP2 exhibit the most stable structures during 100 ns of simulation. Multiple sequence alignment and conservation analysis of Human SFRPs showed that the CRD domain of SFRPs is more conserved than the NTR domain. The docking result indicated that SFRP3 has the highest binding affinity to Wnt3, while SFRP1 and SFRP5 have the lowest. Despite the lower affinity of SFRP1/SFRP5 for Wnt3, a higher positive charge in their NTR domains leads to an increase in their local concentration near the secreting cells and an enhancement in the antagonistic activity. In contrast, SFRP3/SFRP4 can act as an antagonist in distant cells due to less positive regions in their NTR domain and weakly binding to the heparin of the intercellular matrix.","PeriodicalId":16366,"journal":{"name":"Journal of Molecular Evolution","volume":" ","pages":"350-369"},"PeriodicalIF":2.1,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0