Biology subjects

Yi, L.

Publications and source records attributed to Yi, L..

At least 37 records · Page 2Linked to original sources

bioRxiv2024

Synergistic amplifier reprograms biosensor behavior to facilitate detection of dioxin-like compounds

Biosensors are prominent detection tools for evaluating various analytical markers. However, these devices that meet practical application scenarios are still limited, and their potential remains to be developed. In these aspects, we attempted to design and construct a synergistic amplifier consisting of two components, namely, a transcriptional activation component mediated by the Gal3C regulator and a transcription recruitment component exploiting the function of dCas9-(SpyC)n, which work together to enhance yeast biosensor performance. This synergistic amplifier increased the signal output by 5.1-folds and the detection limit by 4.4-folds, respectively, while maintaining adjustable sensitivity and avoiding noise introduction during signal amplification. We demonstrated the use of synergistic amplifier in detecting dioxin analogues, aiming to unlock the potential of predictive modulation, and found that it achieved progress in dynamic output and detection limit. This work show that synergistic amplifier is a new paradigm for expanding signal processing pathways within synthetic genetic networks, enabling cell-based biosensors for environmental monitoring.

molecular biology↗

bioRxiv2024

The effects of 17α-estradiol treatment on endocrine system revealed by single-nucleus transcriptomic sequencing of hypothalamus

In this study, we investigated 17-estradiols role in lifespan extension from long-term administration. Pooled hypothalami from aged male Norway brown rats treated with 17-estradiol (O.T), aged male controls (O), and young male controls (Y) underwent single-nucleus transcriptomic sequencing (snRNA-seq). To evaluate the effects of 17-estradiol on aging neurons, supervised clustering of neurons based on neuropeptides and their receptors were used to evaluate the responses of each neuron subtype during aging and after 17-estradiol treatment. The elevated cellular metabolism, stress and decreased expression levels of pathways involved in synapse formation in neurons initiated by aging were significantly attenuated by 17-estradiol. Assessment of changes in neuron populations showed that neurons related to food intake, reproduction, blood pressure, stress response, and electrolyte balance were sensitive to 17-estradiol treatment. 17-estradiol treatment not only increased serum Oxytocin (Oxt), but also heightened the activity of hypothalamic-pituitary-gonadal (HPG) axis, as evidenced by significantly elevated levels of plasma Gnrh, total testosterone, and decreased estradiol. Elevated Gnrh1 was confirmed to be one of the causal effects mediating the role of 17-estradiol in energy homeostasis, neural synapse, and stress response. Notably, Crh neurons exhibited prominent stressed phenotype in O.T, distinct to appetite-stimulating neurons Agrp and Ghrl. Therefore, the HPG axis and energy metabolism may be key targets of 17-estradiol in male hypothalamus. Additionally, supervised clustering of neurons was shown to be a useful method for assessing treatment responses and cellular perturbation among different neuron subtypes in the hypothalamus.

neuroscience↗

bioRxiv2024

Dihydromyricetin promotes GLP-1 secretion to improve insulin resistance via "gut microbiota-CDCA"

Dihydromyricetin (DHM) is a polyphenolic phytochemical found mainly in plants such as Ampelopsis grossedentata, which has beneficial effects on insulin resistance. However, the specific mechanism has not been clarified. In this study, C57BL/6 mice were exposed to a high-fat diet (HFD) for eight weeks. DHM could improve insulin resistance via enhancing the incretin effect. DHM increased serum GLP-1 by improving intestinal GLP-1 secretion and inhibiting GLP-1 decomposition, associated with the alteration of intestinal intraepithelial lymphocytes (IELs) proportions and decreased expression of CD26 in IELs and TCR{beta}+ CD8{beta}+ IELs in HFD-induced mice. Meanwhile, DHM could ameliorate GLP-1 level and insulin resistance by modulation of gut microbiota and the metabolites, particularly the regulation of intestinal bile acid CDCA content, followed by the inhibition of FXR expression in intestinal L cells as well as increased Gcg mRNA expression and the secretion of GLP-1. These findings clarify the role of the "gut microbiota-CDCA" pathway in the improvement of intestinal GLP-1 levels in HFD-induced mice by DHM administration, providing a new pharmacological target for the prevention of insulin resistance.

pharmacology and toxicology↗

bioRxiv2024

Characterizing interactions of ER resident proteins in situ through the YST-PPI method

The mutual interactions of ER resident proteins in the ER maintain its functions, prompting the protein folding, modification, and transportation. Here, a new method, named YST-PPI (YESS-based Split fast TEV protease System for Protein-protein Interaction) was developed, targeting the characterization of protein interactions in ER. YST-PPI method integrated the YESS system, split-TEV technology and endoplasmic reticulum retention signal peptide (ERS) to provide an effective strategy for studying ER in situ PPIs in a fast and quantitative manner. The interactions among 15 ER resident proteins of S. cerevisiae were explored using the YST-PPI system, and their interaction network map was constructed, in which more than 74 interacting resident protein pairs were identified. Our studies also showed that Lhs1p plays a critical role in regulating the interactions of most of the ER resident proteins, expect the Sil1p, indicating its potential role in controlling the ER molecular chaperones. Moreover, the mutual interaction revealed by our studies further confirmed that the ER resident proteins perform their functions in a synergetic way and multimer complex might be formed during the process.

microbiology↗

bioRxiv2024

Chalkophomycin Biosynthesis Revealing Unique Enzyme Architecture for a Hybrid Nonribosomal Peptide Synthetase and Polyketide Synthase

Chalkophomycin is a novel chalkophore with antibiotic activities isolated from Streptomyces sp. CB00271, while its potential in studying cellular copper homeostasis makes it an important probe and drug lead. The constellation of N-hydroxylpyrrole, 2H-oxazoline, diazeniumdiolate, and methoxypyrrolinone functional groups into one compact molecular architecture capable to coordinate cupric ion draws interest to unprecedented enzymology responsible for chalkophomycin biosynthesis. To elucidate the biosynthetic machinery for chalkophomycin production, the chm biosynthetic gene cluster from S. sp. CB00271 was identified, and its involvement in chalkophomycin biosynthesis was confirmed by gene replacement. The chm cluster was localized to a [~]31 kb DNA region, consisting of 19 open reading frames that encode five non-ribosomal peptide synthetase (ChmHIJLO), one modular polyketide synthases (ChmP), six tailoring enzymes (ChmFGMNQR), two regulatory proteins (ChmAB), and four resistance proteins (ChmA'CDE). A model for chalkophomycin biosynthesis is proposed based on functional assignments from sequence analysis and structure modelling, and is further supported by analogy to over 100 chm-type gene clusters in public databases. Our studies thus set the stage to fully investigate chalkophomycin biosynthesis and to engineer chalkophomycin analogues through a synthetic biology approach.

biochemistry↗

bioRxiv2024

Beyond over- or under-sampling: autistic children's inflexibility in sampling costly information

BackgroundEfficient information sampling is crucial for human inference and decision-making, even for young children. Information sampling is also closely associated with the core symptoms of autism spectrum disorder (ASD), since both the social interaction difficulties and repetitive behaviors suggest that autistic people may sample information from the environment distinctively. Previous research on information sampling in ASD focused mainly on adolescents and adults, and on whether they over- or under-sample. The specific ways in which autistic children sample information, especially when facing explicit costs and adapting to environmental changes, remain unclear. MethodsWe employed an adapted bead task to investigate the sampling behavior of 24 autistic and 41 neurotypical children, matched for age and IQ. In each trial of our experiment, children gathered information about an unknown target isle by drawing samples from it and then guessed the target between two isles based on their samples. In conditions where sampling was costly, children needed to weigh the benefits of information against the costs of acquiring additional samples. Through computational modeling and intricate behavioral measures, we revealed how the two groups of children differed in sampling decisions and underlying cognitive mechanisms. ResultsUnder conditions involving costs, autistic children showed less efficient sampling than their neurotypical peers. This inefficiency was due to their increased variability in the number of samples taken across trials rather than a systematic bias. Computational models indicated that while both groups shared a similar decision process, autistic childrens sampling decisions were less influenced by dynamic changes and more driven by recent evidence, thus leading to their increased sampling variation and reduced efficiency. LimitationsTo refine ASD subtyping and correlate symptom severity with behavioral characteristics and computational findings, future research may need larger participant groups and more comprehensive clinical assessments. ConclusionsThis study reveals an inefficiency of autistic children in information sampling and tracks down this inefficiency to their increased sampling variability, primarily due to their cognitive preference for more local and static information. These findings are consistent with several influential behavioral theories of ASD and highlight the needs of a multi-level understanding of cognitive flexibility in ASD.

neuroscience↗

bioRxiv2024

A Combinatorial Strategy for HRV 3C Protease Engineering to Achieve the N-terminal Free Cleavage

Human rhinovirus 3C protease (HRV 3C-P) has a high specificity against the substrate of LEVLFQ{downarrow}G at P1 site, which plays an important role in biotechnology and academia as a fusion tag removal tool. However, a non-ignorable limitation is that an extra residue of Gly would remain at the N terminus of the recombinant target protein after cleavage with HRV 3C-P, thus potentially causing protein mis-functionality or immunogenicity. Here, we developed a combinatorial strategy by integrating structure-guided library design and high-throughput screening of eYESS approach for HRV 3C-P engineering to expand its P1 specificity. Finally, a C3 variant was obtained, exhibiting a broad substrate P1 specificity to recognize 20 different amino acids with the highest activity against LEVLFQ{downarrow}M (kcat/KM= 3.72 {+/-} 0.04 mM-1{middle dot}s-1). Further biochemical and NGS-mediated substrate profiling analysis showed that C3 variant still kept its substrate stringency at P1 site and good residue tolerance at P2 site, but with an expanded P1 specificity. Structural simulation of C3 indicated a reconstructed S1 binding pocket as well as new interactions with the substrates. Overall, our studies here prompt not only the practical applications and understanding of substrate recognition mechanisms of HRV 3C-P, also provide new tools for other enzyme engineering. Abstract graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/574269v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@b891eborg.highwire.dtl.DTLVardef@174151dorg.highwire.dtl.DTLVardef@1656f4org.highwire.dtl.DTLVardef@a6c1bb_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2023

Single-cell 5' RNA sequencing of camelid peripheral B cells reveals cellular basis of heavy-chain antibody production

Camelids are capable of producing both conventional tetrameric antibodies (Abs) and dimeric heavy-chain antibodies (HCAbs). While B cells generating these two types of Abs exhibit distinct B-cell receptors (BCRs), it remains unclear whether these two B cell populations differ in their phenotypes and developmental processes. Here, we collected eight PBMC samples before and after immunization from four Bactrian camels and conducted single-cell 5 RNA sequencing. We characterized the functional subtypes and differentiation trajectories of circulating B cells in camels, including native B cells, memory B cells, intermediate B cells, atypical B cells, and plasma cells. Additionally, we reconstructed single-cell BCR sequences and revealed the IGHV and IGHC gene types. We found that B cells expressing variable genes of HACbs (VHH) were widely present in various functional subtypes and showed highly overlapping differentiation trajectories to B cells expressing variable genes of conventional Abs (VH). After immunization, the transcriptional changes in VHH+ and VH+ B cells were also largely consistent. Our study elucidates the cellular context of HCAb production in camels, and lays the foundation for the development of single B cell-based nanobody screening.

genomics↗

bioRxiv2023

Computational design of N-linked glycans for high throughput epitope profiling

Efficient identification of epitopes is crucial for drug discovery and design as it enables the selection of optimal epitopes, expansion of lead antibody diversity, and verification of binding interface. Although high resolution low throughput methods like X-ray crystallography can determine epitopes or protein-protein interactions accurately, they are time-consuming and can only be applied to a limited number of complexes. To overcome these limitations, we have developed a rapid computational method that incorporates N-linked glycans to mask epitopes or protein interaction surfaces, thereby providing an atomistic mapping of these regions. Using human coagulation factor IXa (fIXa) as a model system, we could rapidly and reliably delineate epitopes through the insertion of N-linked glycans that efficiently disrupt binding in a site-selective manner. To validate the efficacy of our method, we conducted ELISA experiments and high-throughput yeast surface display assays. Furthermore, X-ray crystallography was employed to verify the results, thereby recapitulating through the method of N-linked glycans an atomistic resolution mapping of the epitope.

bioengineering↗

bioRxiv2023

Temporal landscape and translational regulation of A-to-I editing in mouse retina development

The significance of A-to-I RNA editing in neurological development is widely recognized, however, its influence on retina development remains to be thoroughly understood. In this study, we aimed to characterize the temporal landscape of A-to-I editing in mouse retina development using total RNA-seq and Ribosome profiling, with a specific emphasis on its effect on gene translation. Our findings revealed that the editing underwent plastic changes and distinct editing contents facilitated stage-specific functions. Further analysis showed a dynamic interplay between A-to-I editing and alternative splicing, with A-to-I editing having a significant impact on splicing efficiency and increasing the quantity of splicing events. A-to-I editing held the potential of enhancing the translatomes diversity, but this came at the expense of reduced translational efficiency. When coupled with splicing, it could produce a coordinated regulatory effect on translatome dynamics. Overall, our study presents a temporally resolved atlas of A-to-I editing, connecting its dynamic changes with the regulatory impact on splicing and translation.

neuroscience↗

bioRxiv2022

Subchronic oral toxicity study of Aldicarb sulfoxide in Sprague-Dawley rats

Aldicarb sulfoxide is the metabolite of the exceedingly deadly carbamate insecticide Aldicarb. Aldicarb sulfoxide is easily soluble in water and has been identified in groundwater. Moreover, Aldicarb sulfoxide is highly hazardous to mammals. However, the toxicity data of Aldicarb sulfoxide is scarce. Here, the effects of relatively low dosages of exposure to Aldicarb sulfoxide on the blood biochemical, hematological, and histopathological parameters were examined in SD rats. The rats were treated with Aldicarb sulfoxide orally at dosages of 0, 6.3, 18.9, and 56.7 g per kg b.w. daily for 12 weeks. The results revealed that Aldicarb sulfoxide induced significant alterations in liver-related biochemical parameters, glucose level, cholesterol level, and uric acid level. Histopathological testing demonstrated cellular alterations in the liver of 18.9 and 56.7 g/kg BW. Together, our data demonstrated that Aldicarb sulfoxide exposure causes liver injury. Furthermore, the no observed adverse effect level (NOAEL) was less than 6.3 g/kg BW, and the lowest benchmark dose (BMD) value was 0.03 g/kg BW. Accordingly, Aldicarb sulfoxides derived no-effect level (DNEL) was calculated as 0.00035 g/kg BW. Thus, this work is an important reference for supervising Aldicarb sulfoxide in the environment and determining safe exposure limits for Aldicarb sulfoxide.

pharmacology and toxicology↗

bioRxiv2022

Tumor suppressor p53 deficiency increases tumor immunogenicity through promoting IL33-mediated anti-tumor immune responses

Recent studies have shown that p53 contributes to poor survival during immune checkpoint blockade (ICB) therapy. Lung cancer patients with p53 mutations have significantly improved response rates to PD-1 ICB therapy. While previous studies have shown that tumor-derived IL-33 is required for the anti-tumor immune response and efficacy of ICB therapies, the relationship between p53 and IL-33 during ICB therapy is unknown. In this study, we characterized the role of the p53/IL-33 axis in regulating the tumor microenvironment (TME) in response to ICB therapy. CRISPR-Cas9-mediated deletion of Trp53 in tumor cells combined with PD-1 ICB therapy synergistically inhibited tumor growth in a murine MC38 colon adenocarcinoma model. We observed increased CD4+ and CD8+ T cell infiltration, as well as reduced Treg infiltration. IL-33 was upregulated and its expression increased with time and response to treatment. Simultaneous deletion of Il33 in the MC38 tumor cells reversed the efficacy of PD-1 ICB therapy. ST2-/-(IL-33 receptor) mice with Trp53-deficient MC38 tumors also showed no response to PD-1 ICB. Our findings depict a novel mechanism by which the loss of p53 in tumors treated with ICB therapy induces upregulation of tumoral IL-33 and host ST2 signaling. p53 mutations may be a double-edged sword for cancer, i.e. loss of the tumor suppressor initially facilitates tumorigenesis, but also leads to upregulation of danger signals in the tumor. These danger signals, such as IL-33, mediate the anti-tumor effect of ICB.

immunology↗

bioRxiv2022

Spatial compartmentalization of signalling imparts source-specific functions on secreted factors

Efficient regeneration requires multiple cell types acting in a coordination. To better understand the intercellular networks involved and how they change when regeneration fails, we profiled the transcriptome of hematopoietic, stromal, myogenic, and endothelial cells over 14 days following acute muscle damage. A time-resolved computational model of interactions was generated, and VEGFA-driven endothelial engagement was identified as a key differentiating feature in models of successful and failed regeneration. In addition, it revealed that the majority of secreted signals, including VEGFA, are simultaneously produced by multiple cell types. To test whether the cellular source of a factor determines its function, we deleted VEGFA from two cell types residing in close proximity, stromal and myogenic progenitors. By comparing responses to different types of damage, we found that myogenic and stromal VEGFA have distinct functions in regeneration. This suggests that spatial compartmentalization of signaling plays a key role in intercellular communication networks. HighlightsO_LILigand-receptor signaling redundancy during skeletal muscle regeneration C_LIO_LIInflammatory cells, and muscle and fibro/adipogenic progenitors produce VEGFA C_LIO_LIVEGFA from muscle progenitors control their proliferation after muscle damage C_LIO_LIVEGFA from FAP controls angiogenesis only after ischemic damage C_LI eTOC blurbGroppa et al. performed a novel time-resolved bioinformatics analysis that revealed extensive ligand-receptor redundancy among the cell types contributing to skeletal muscle regeneration. They focused on one of these pathways, and showed that VEGFA from different cell types has distinct roles in regeneration.

cell biology↗

bioRxiv2022

CircRNA_33702 promotes renal fibrosis by targeting the miR-29b-3p/WISP1 pathway

Growing evidence suggest that circular RNAs (circRNAs) are critical mediators in renal diseases. However, there have been very few reports about the role of circRNAs in renal fibrosis. In this study, circRNA_33702 was found to be upregulated, both in UUO mice and in TGF-{beta} 1-treated BUMPT cells. Whilst knockdown of circRNA_33702 was shown to relieve the TGF-{beta} 1-induced expression of collagen I, collagen III and fibronectin; overexpression of circRNA_33702 was found to exert an inhibitory effect on the expression of the same genes. Mechanistically, circRNA_33702 was demonstrated to bind directly with miR-29b-3p and inhibit its expression. Moreover, WISP1 was identified as a target of miR-29b-3p and the expression of WISP1 was observed to be repressed by miR-29b-3p. Notably, knockdown of circRNA_33702 was found to attenuate the expression of collagen I, collagen III and fibronectin by inhibiting the expression of WISP1, and the observed inhibitory effect can be reversed by miR-29b-3p inhibitor. Finally, inhibition of circRNA_33702 was shown to attenuate interstitial fibrosis in UUO mice via the miR-29b-3p/WISP1 axis. In general, our data show that circRNA_33702 may promote renal fibrosis via the miR-29b-3p/WISP1 axis, which may potentially be developed as a new therapeutic target.

molecular biology↗

bioRxiv2022

Proteomic Dissection of a Giant Cell

Many individual proteins have been identified as having defined positions relative to cell polarity axes, raising the question of what fraction of all proteins may have polarized localizations. We took advantage of the giant ciliate Stentor coeruleus to quantify the extent of polarized localization proteome-wide. This trumpet-shaped unicellular organism shows a clear morphological anterior-posterior axis defined by a circular array of cilia known as a membranellar band at one end, and a holdfast at the other end. Because individual Stentor cells are over a millimeter in length, we were able to cut the cells into three pieces along the anterior-posterior axis, followed by proteomic analysis of proteins enriched in each piece. We find that approximately 30% of all detected proteins show a polarized location relative to the anterior-posterior cell axis. Proteins with polarized enrichment include centrin-like proteins, calcium-regulated kinases, orthologs of SFI1 and GAS2, and proteases. At the organelle level, nuclear and mitochondrial proteins are enriched in the anterior half of the cell body, but not in the membranellar band itself, while ribosome related proteins are apparently uniformly distributed. RNAi of signaling proteins enriched in the membranellar band, which is the anterior-most structure in the cell, revealed a protein phosphatase 2 subunit b ortholog required for closure of the membranellar band into the ring shape characteristic of Stentor. These results suggest that a large fraction of the Stentor proteome has a polarized localization, and provide a protein-level framework for future analysis of pattern formation and regeneration in Stentor as well as defining a general strategy for subcellular spatial proteomics based on physical dissection of cells.

cell biology↗

bioRxiv2021

PixR, a novel activator of conjugative transfer of IncX4 resistance plasmids, mitigates the fitness cost of mcr-1 carriage in Escherichia coli

The emergence of the plasmid-borne colistin resistance gene mcr-1 threats public health. IncX4-type plasmids are one of the most epidemiologically successful vehicles for spreading mcr-1 worldwide. Since MCR-1 is known for imposing a fitness cost to its host bacterium, the successful spread of mcr-1-bearing plasmids might be linked to high conjugation frequency, which would enhance the maintenance of the plasmid in the host without antibiotic selection. However, the mechanism of IncX4 plasmids conjugation remains unclear. In this study, we used high-density transposon mutagenesis to identify factors required for IncX4 plasmid transfer and 18 genes were identified, including five with annotations unrelated to conjugation. The Cappable-seq and RNA-seq analysis confirmed that a novel transcriptional regulator gene, pixR, directly regulates the transfer of IncX4 plasmids by binding the promoter of 13 essential transfer genes to increase their transcription. Plasmid invasion and co-culture competition assays revealed that pixR is essential for the spread and persistence of mcr-1-bearing IncX4 plasmids in bacterial populations, and effective conjugation is crucial for alleviating the fitness cost exerted by mcr-1 carriage. The existence of the IncX4-specific pixR gene increases plasmid transmissibility while promoting the invasion and persistence of mcr-1-bearing plasmids in bacterial populations, which helps explain their global prevalence. IMPORTANCEThe spread of clinical important antibiotic resistance genes is frequently related to some epidemic plasmids. However, the underlying molecular mechanisms contributing to the successful spread of these epidemic plasmids remains unclear. The significant of our research indicated that efficient conjugation could promote the invasion and persistence of plasmids within a bacterial population, resulting in the successful dissemination of epidemic plasmids in nature. Our data also highlight the importance of developing plasmid conjugation inhibitors to solve the antibiotic resistance crisis.

microbiology↗

bioRxiv2021

Detection of precisely edited CRISPR/Cas9 alleles through cointroduced restriction-fragment length polymorphisms

CRISPR/Cas9 is a powerful tool for producing genomic insertions and deletions (indels) to interrogate gene function. Modified CRISPR/Cas9 protocols can produce targeted genetic changes that are more precise than indels, but founder recovery is less efficient. Focusing on producing missense mutations in zebrafish using single-stranded oligo deoxynucleotide (ssODN) donor templates, we pioneered a strategy of adding synonymous changes to create novel restriction-enzyme (RE) sites, allowing detection of rare precise edits in a modified fluorescent-PCR fragment assay. We have named this process TIARS (test for incorporation of added recognition sites). Aided by TIARS, we induced two distinct amino-acid substitutions (T979I and P1387S) in the atp7a gene among somatic tissues of CRISPR-Cas9-treated F0 zebrafish. One of these F0s transmitted the allele to atp7aT979I/+ F1 progeny, and trans-heterozygosity of this allele against a null atp7a allele causes hypopigmentation, consistent with more severe pigment deficits in zebrafish or humans carrying only null mutations in atp7a/ATP7A. Design of ssODNs with novel RE recognition sites is labor-intensive, so we developed an in silico tool, TIARS Designer, and performed bioinformatic validation indicating that TIARS should be generalizable to other genes and experimental systems that employ donor template DNA.

genetics↗

bioRxiv2021

A novel approach to comparative RNA-Seq does not support a conserved set of genes underlying animal regeneration

Molecular studies of animal regeneration typically focus on conserved genes and signaling pathways that underlie morphogenesis. To date, a holistic analysis of gene expression across animals has not been attempted, as it presents a suite of problems related to differences in experimental design and gene homology. By combining orthology analysis with a novel statistical method for testing gene enrichment across large datasets, we are able to test whether biological processes across organisms share transcriptional regulation. We applied this method to six publicly available RNA-seq datasets from diverse examples of animal regeneration. We recovered 160 conserved orthologous gene clusters, which are enriched in structural genes as opposed to those regulating morphogenesis. A breakdown of gene presence/absence provides only limited support for the conservation of pathways typically implicated in regeneration, such as Wnt signaling and cell pluripotency. Specifically, these pathways are only conserved if we allow gene paralogs to be interchangeable through evolution. Overall, our analysis does not support the hypothesis that a shared set of ancestral genes underlie regeneration mechanisms in animals. The methods described in this paper will be broadly applicable for studying the genetic underpinnings of traits across distantly related organisms.

evolutionary biology↗