Regressive Evolution of Pigmentation in the Cavefish Astyanax

2006 ◽  
Vol 52 (3-4) ◽  
pp. 405-422 ◽  
Author(s):  
William R. Jeffery
Keyword(s):  
Neural Crest ◽  
Single Gene ◽  
Pigment Cells ◽  
Loss Of Function ◽  
Coding Region ◽  
Protein Coding ◽  
Regressive Evolution ◽  
Astyanax Mexicanus ◽  
Key Enzyme ◽  
Surface Dwelling

Many cave animals are colorless due to loss of pigment cells. Here, we review recent progress on how and why pigmentation has disappeared in Astyanax mexicanus, a single teleost species with conspecific surface-dwelling (surface fish) and many different cave-dwelling (cavefish) forms. During surface fish development, migratory neural crest cells form three types of pigment cells: silver iridophores, orange xanthophores, and black melanophores. Cavefish have eliminated or substantially reduced their complement of melanophores and exhibit albinism, loss of the capacity to synthesize melanin. Cell tracing, immunolocalization, and neural tube explant cultures show that cavefish have retained a colorless pre-melanophore (melanoblast) lineage derived from the neural crest. Thus, the cavefish neural crest produces melanoblasts that migrate normally but are blocked in differentiation and show defective melanogenesis. Cavefish melanoblasts can convert exogenous L-DOPA into melanin and therefore have active tyrosinase, the key enzyme in melanogenesis. In contrast, cavefish melanoblasts are unable to convert L-tyrosine to L-DOPA (and melanin), although this reaction is also catalyzed by tyrosinase. Thus, cavefish are tyrosinase-positive albinos that have a deficiency in L-tyrosine transport or utilization within the melanosome, the organelle in which melanin is synthesized. At least five different types of Astyanax cavefish show the same defect in melanogenesis. Genetic analysis shows that cavefish albinism is caused by loss of function mutations in a single gene, p/oca2, which encodes a large protein that probably spans the melanosome membrane. Different deletions in the p/oca2 protein-coding region are responsible for loss of function in at least two different cavefish populations, suggesting that albinism evolved by convergence. Based on current understanding of the genetic basis of albinism, we discuss potential mechanisms for regressive evolution of cavefish pigmentation.

scholarly journals ALKALs are in vivo ligands for ALK family receptor tyrosine kinases in the neural crest and derived cells

2018 ◽  
Vol 115 (4) ◽  
pp. E630-E638 ◽  
Author(s):  
Andrey Fadeev ◽  
Patricia Mendoza-Garcia ◽  
Uwe Irion ◽  
Jikui Guan ◽  
Kathrin Pfeifer ◽  
...  
Keyword(s):  
Neural Crest ◽  
Tyrosine Kinases ◽  
Pigment Cells ◽  
Loss Of Function ◽  
Pediatric Tumor ◽  
Downstream Signaling ◽  
Receptor Complexes ◽  
Anaplastic Lymphoma ◽  
Biochemical Analyses

Mutations in anaplastic lymphoma kinase (ALK) are implicated in somatic and familial neuroblastoma, a pediatric tumor of neural crest-derived tissues. Recently, biochemical analyses have identified secreted small ALKAL proteins (FAM150, AUG) as potential ligands for human ALK and the related leukocyte tyrosine kinase (LTK). In the zebrafish Danio rerio, DrLtk, which is similar to human ALK in sequence and domain structure, controls the development of iridophores, neural crest-derived pigment cells. Hence, the zebrafish system allows studying Alk/Ltk and Alkals involvement in neural crest regulation in vivo. Using zebrafish pigment pattern formation, Drosophila eye patterning, and cell culture-based assays, we show that zebrafish Alkals potently activate zebrafish Ltk and human ALK driving downstream signaling events. Overexpression of the three DrAlkals cause ectopic iridophore development, whereas loss-of-function alleles lead to spatially distinct patterns of iridophore loss in zebrafish larvae and adults. alkal loss-of-function triple mutants completely lack iridophores and are larval lethal as is the case for ltk null mutants. Our results provide in vivo evidence of (i) activation of ALK/LTK family receptors by ALKALs and (ii) an involvement of these ligand–receptor complexes in neural crest development.

scholarly journals A hypomorphic cystathionine ß-synthase gene contributes to cavefish eye loss by disrupting optic vasculature

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Li Ma ◽  
Aniket V. Gore ◽  
Daniel Castranova ◽  
Janet Shi ◽  
Mandy Ng ◽  
...  
Keyword(s):  
Circulatory System ◽  
Astyanax Mexicanus ◽  
Transsulfuration Pathway ◽  
Key Enzyme ◽  
Surface Dwelling ◽  
Blind Cave ◽  
Vestigial Structures ◽  
Key Indicators ◽  
Evolutionary Descent ◽  
Eye Formation

Abstract Vestigial structures are key indicators of evolutionary descent, but the mechanisms underlying their development are poorly understood. This study examines vestigial eye formation in the teleost Astyanax mexicanus, which consists of a sighted surface-dwelling morph and multiple populations of blind cave morphs. Cavefish embryos initially develop eyes, but they subsequently degenerate and become vestigial structures embedded in the head. The mutated genes involved in cavefish vestigial eye formation have not been characterized. Here we identify cystathionine ß-synthase a (cbsa), which encodes the key enzyme of the transsulfuration pathway, as one of the mutated genes responsible for eye degeneration in multiple cavefish populations. The inactivation of cbsa affects eye development by increasing the transsulfuration intermediate homocysteine and inducing defects in optic vasculature, which result in aneurysms and eye hemorrhages. Our findings suggest that localized modifications in the circulatory system may have contributed to the evolution of vestigial eyes in cavefish.

scholarly journals Different Domains of Phytophthora sojae Effector Avr4/6 Are Recognized by Soybean Resistance Genes Rps4 and Rps6

2010 ◽  
Vol 23 (4) ◽  
pp. 425-435 ◽  
Author(s):  
Daolong Dou ◽  
Shiv D. Kale ◽  
Tingli Liu ◽  
Qinghua Tang ◽  
Xia Wang ◽  
...  
Keyword(s):  
Protein Translocation ◽  
Single Gene ◽  
Phytophthora Sojae ◽  
Avirulence Genes ◽  
Coding Region ◽  
Nucleotide Substitutions ◽  
Protein Coding ◽  
C Terminus ◽  
Oomycete Pathogen ◽  
Soybean Leaves

At least 12 avirulence genes have been genetically identified and mapped in Phytophthora sojae, an oomycete pathogen causing root and stem rot of soybean. Previously, the Avr4 and Avr6 genes of P. sojae were genetically mapped within a 24 kb interval of the genome. Here, we identify Avr4 and Avr6 and show that they are actually a single gene, Avr4/6, located near the 24-kb region. Avr4/6 encodes a secreted protein of 123 amino acids with an RXLR-dEER protein translocation motif. Transient expression of Avr4/6 in soybean leaves revealed that its gene product could trigger a hypersensitive response (HR) in the presence of either Rps4 or Rps6. Silencing Avr4/6 in P. sojae stable transformants abolished the avirulence phenotype exhibited on both Rps4 and Rps6 soybean cultivars. The N terminus of Avr4/6, including the dEER motif, is sufficient to trigger Rps4-dependent HR while its C terminus is sufficient to trigger Rps6-mediated HR. Compared with alleles from avirulent races, alleles of Avr4/6 from virulent races possess nucleotide substitutions in the 5′ untranslated region of the gene but not in the protein-coding region.

scholarly journals A Hypomorphic Cystathionine ß-Synthase Gene Contributes to Cavefish Eye Loss by Disrupting Optic Vasculature

2019 ◽  
Author(s):  
Li Ma ◽  
Aniket V. Gore ◽  
Daniel Castranova ◽  
Janet Shi ◽  
Mandy Ng ◽  
...  
Keyword(s):  
Oxygen Deficiency ◽  
Circulatory System ◽  
Astyanax Mexicanus ◽  
Transsulfuration Pathway ◽  
Key Enzyme ◽  
Surface Dwelling ◽  
Blind Cave ◽  
Different Populations ◽  
Key Indicators ◽  
Blind Cavefish

AbstractVestigial structures are key indicators of evolutionary descent but the mechanisms underlying their development are poorly understood. This study examines vestigial eye formation in the teleost Astyanax mexicanus, which consists of a sighted surface-dwelling morph and different populations of blind cave morphs. Cavefish embryos initially develop optic primordia but vestigial eyes are formed during larval development. Multiple genetic factors are involved in cavefish eye loss but none of the mutated genes have been identified. Here we identify cystathionine ß-synthase (cbsa), which encodes the key enzyme of the transsulfuration pathway, as a mutated gene responsible for eye degeneration in multiple cavefish populations. The inactivation of cbsa affects eye development by inducing accumulation of the transsulfuration intermediate homocysteine and defects in optic vasculature, including aneurysms and eye hemorrhages, leading to oxygen deficiency. Our findings suggest that localized modifications in the circulatory system and hypoxia had important roles in the evolution of vestigial eyes in blind cavefish.

scholarly journals DeepPheno: Predicting single gene loss-of-function phenotypes using an ontology-aware hierarchical classifier

2019 ◽  
Author(s):  
Maxat Kulmanov ◽  
Robert Hoehndorf
Keyword(s):  
Research Group ◽  
Molecular Mechanisms ◽  
State Of The Art ◽  
Single Gene ◽  
Hierarchical Classification ◽  
Model Organisms ◽  
Loss Of Function ◽  
Protein Coding ◽  
Disease Associations ◽  
Molecular Aberrations

AbstractMotivationPredicting the phenotypes resulting from molecular perturbations is one of the key challenges in genetics. Both forward and reverse genetic screen are employed to identify the molecular mechanisms underlying phenotypes and disease, and these resulted in a large number of genotype–phenotype association being available for humans and model organisms. Combined with recent advances in machine learning, it may now be possible to predict human phenotypes resulting from particular molecular aberrations.ResultsWe developed DeepPheno, a neural network based hierarchical multi-class multi-label classification method for predicting the phenotypes resulting from complete loss-of-function in single genes. DeepPheno uses the functional annotations with gene products to predict the phenotypes resulting from a loss-of-function; additionally, we employ a two-step procedure in which we predict these functions first and then predict phenotypes. Prediction of phenotypes is ontology-based and we propose a novel ontology-based classifier suitable for very large hierarchical classification tasks. These methods allow us to predict phenotypes associated with any known protein-coding gene. We evaluate our approach using evaluation metrics established by the CAFA challenge and compare with top performing CAFA2 methods as well as several state of the art phenotype prediction approaches, demonstrating the improvement of DeepPheno over state of the art methods. Furthermore, we show that predictions generated by DeepPheno are applicable to predicting gene–disease associations based on comparing phenotypes, and that a large number of new predictions made by DeepPheno interact with a gene that is already associated with the predicted phenotype.Availabilityhttps://github.com/bio-ontology-research-group/[email protected]

scholarly journals DeepPheno: Predicting single gene loss-of-function phenotypes using an ontology-aware hierarchical classifier

2020 ◽  
Vol 16 (11) ◽  
pp. e1008453
Author(s):  
Maxat Kulmanov ◽  
Robert Hoehndorf
Keyword(s):  
Molecular Mechanisms ◽  
Single Gene ◽  
Hierarchical Classification ◽  
Model Organisms ◽  
Loss Of Function ◽  
Protein Coding ◽  
Functional Annotations ◽  
Step Procedure ◽  
Disease Associations ◽  
Molecular Aberrations

Predicting the phenotypes resulting from molecular perturbations is one of the key challenges in genetics. Both forward and reverse genetic screen are employed to identify the molecular mechanisms underlying phenotypes and disease, and these resulted in a large number of genotype–phenotype association being available for humans and model organisms. Combined with recent advances in machine learning, it may now be possible to predict human phenotypes resulting from particular molecular aberrations. We developed DeepPheno, a neural network based hierarchical multi-class multi-label classification method for predicting the phenotypes resulting from loss-of-function in single genes. DeepPheno uses the functional annotations with gene products to predict the phenotypes resulting from a loss-of-function; additionally, we employ a two-step procedure in which we predict these functions first and then predict phenotypes. Prediction of phenotypes is ontology-based and we propose a novel ontology-based classifier suitable for very large hierarchical classification tasks. These methods allow us to predict phenotypes associated with any known protein-coding gene. We evaluate our approach using evaluation metrics established by the CAFA challenge and compare with top performing CAFA2 methods as well as several state of the art phenotype prediction approaches, demonstrating the improvement of DeepPheno over established methods. Furthermore, we show that predictions generated by DeepPheno are applicable to predicting gene–disease associations based on comparing phenotypes, and that a large number of new predictions made by DeepPheno have recently been added as phenotype databases.

scholarly journals ALKALs are in vivo ligands for ALK family Receptor Tyrosine Kinases in the neural crest and derived cells

2017 ◽  
Author(s):  
Andrey Fadeev ◽  
Patricia Mendoza Garcia ◽  
Uwe Irion ◽  
Jikui Guan ◽  
Kathrin Pfeifer ◽  
...  
Keyword(s):  
Neural Crest ◽  
Tyrosine Kinases ◽  
Pigment Cells ◽  
Loss Of Function ◽  
Receptor Complexes ◽  
Anaplastic Lymphoma ◽  
Zebrafish Larvae ◽  
Neural Crest Development ◽  
Biochemical Analyses

AbstractMutations in Anaplastic Lymphoma Kinase (ALK) are implicated in somatic and familial neuroblastoma, a paediatric tumour of neural crest-derived tissues. Recently, biochemical analyses have identified secreted small ALKAL proteins (FAM150, AUG) as potential ligands for human ALK and the related Leukocyte Tyrosine Kinase (LTK). In the zebrafish Danio rerio, DrLtk, which is similar to human ALK in sequence and domain structure, controls the development of iridophores, neural crest-derived pigment cells. Hence, the zebrafish system allows studying Alk/Ltk and Alkals involvement in neural crest regulation in vivo. Using zebrafish pigment pattern formation, Drosophila eye patterning, and cell culture-based assays, we show that zebrafish Alkals potently activate zebrafish Ltk and human ALK driving downstream signalling events. Overexpression of the three Dr Alkals cause ectopic iridophore development whereas loss of function alleles lead to spatially distinct patterns of iridophore loss in zebrafish larvae and adults. alkal loss of function triple mutants completely lack iridophores and are larval lethal as is the case for ltk null mutants. Our results provide the first in vivo evidence of (i) activation of ALK/LTK family receptors by ALKALs and (ii) an involvement of these ligand-receptor complexes in neural crest development.

scholarly journals LINC01089 functions as a ceRNA for miR-152-3p to inhibit non‐small lung cancer progression through regulating PTEN

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Huixian Zhang ◽  
Hao Zhang ◽  
Xingya Li ◽  
Siyuan Huang ◽  
Qianqian Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Progression ◽  
Expression Level ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Protein Coding ◽  
Tensin Homolog ◽  
Pten Mrna

Abstract Background Long non-coding RNAs (lncRNAs) have been reported to exert crucial functions in regulating the progression of human cancers. However, the function and mechanism of long intergenic non-protein coding RNA 01089 (LINC01089) in non-small cell lung cancer (NSCLC) have not been revealed. Methods The expression level of LINC01089, microRNA (miRNA, miR)-152-3p and phosphatase and tensin homolog deleted onc hromosome ten (PTEN) mRNA was detected by quantitative real-time PCR (qRT-PCR). After gain-of-function and loss-of-function models were established with NSCLC cell lines, the proliferation, migration and invasion of NSCLC cells were detected by cell counting kit-8 (CCK-8) assay, scratch healing assay, Transwell assay, respectively. Dual luciferase reporter assay was employed to validate the binding relationship between miR-152-3p and LINC01089 or the 3’UTR of PTEN. Western blot was used to detect PTEN expression in NSCLC cells after LINC01089 and miR-152-3p were selectively modulated. Results LINC01089 was down-regulated in NSCLC tissues and cells. Functional experiments showed that knockdown of LINC01089 could promote the proliferation, migration and invasion of NSCLC cells, while over-expression of LINC01089 had the opposite effects. miR-152-3p was identified as a functional target for LIN01089, and miR-152-3p could reverse the function of LINC01089. Additionally, LINC01089 could up-regulate the expression level of PTEN via repressing miR-152-3p. Conclusions Down-regulation of LINC01089 promoted the progression of NSCLC through regulating miR-152-3p/PTEN axis.

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