RESUMEN
Uric acid is the main means of nitrogen excretion in uricotelic vertebrates (birds and reptiles) and the end product of purine catabolism in humans and a few other mammals. While uricase is inactivated in mammals unable to degrade urate, the presence of orthologous genes without inactivating mutations in avian and reptilian genomes is unexplained. Here we show that the Gallus gallus gene we name cysteine-rich urate oxidase (CRUOX) encodes a functional protein representing a unique case of cysteine enrichment in the evolution of vertebrate orthologous genes. CRUOX retains the ability to catalyze urate oxidation to hydrogen peroxide and 5-hydroxyisourate (HIU), albeit with a 100-fold reduced efficiency. However, differently from all uricases hitherto characterized, it can also facilitate urate regeneration from HIU, a catalytic property that we propose depends on its enrichment in cysteine residues. X-ray structural analysis highlights differences in the active site compared to known orthologs and suggests a mechanism for cysteine-mediated self-aggregation under H2O2-oxidative conditions. Cysteine enrichment was concurrent with the transition to uricotelism and a shift in gene expression from the liver to the skin where CRUOX is co-expressed with ß-keratins. Therefore, the loss of urate degradation in amniotes has followed opposite evolutionary trajectories: while uricase has been eliminated by pseudogenization in some mammals, it has been repurposed as a redox-sensitive enzyme in the reptilian skin.
Asunto(s)
Cisteína , Reptiles , Piel , Urato Oxidasa , Animales , Cisteína/genética , Peróxido de Hidrógeno , Piel/enzimología , Urato Oxidasa/genética , Urato Oxidasa/metabolismo , Ácido Úrico , Pollos/genética , Reptiles/genética , Reptiles/metabolismoRESUMEN
General cellular aspects of skin development in vertebrates are presented with emphasis on the epidermis of sauropsids. Anamniote skin develops into a multilayered mucogenic and soft keratinized epidermis made of Intermediate Filament Keratins (IFKs) that is reinforced in most fish and few anurans by dermal bony and fibrous scales. In amniotes, the developing epidermis in contact with the amniotic fluid initially transits through a mucogenic phase recalling that of their anamniotes progenitors. A new gene cluster termed EDC (Epidermal Differentiation Complex) evolved in amniotes contributing to the origin of the stratum corneum. The EDC contains numerous genes coding for over 100 types of corneous proteins (CPs). In sauropsids 2-8 layers of embryonic epidermis accumulate soft keratins (IFKs) but do not form a compact corneous layer. The embryonic epidermis of reptiles and birds produces small amount of other, poorly known proteins in addition to IFKs and mucins. In the following development, a resistant corneous layer is formed underneath the embryonic epidermis that is shed before hatching. The definitive corneous epidermis of sauropsids is mainly composed of CBPs (Corneous beta proteins, formerly indicated as beta-keratins) derived from the EDC. CBPs belong to a gene sub-family of CPs unique for sauropsids, contain an inner amino acid region formed by beta-sheets, are rich in cysteine and glycine, and make most of the protein composition of scales, claws, beaks and feathers. In mammalian epidermis CPs missing the beta-sheet region are instead produced, and include loricrin, involucrin, filaggrin and various cornulins. Small amount of CPs accumulate in the 2-3 layers of mammalian embryonic epidermis and their appendages, that is replaced with the definitive corneous layers before birth. Differently from sauropsids, mammals utilize KAPs (keratin associated proteins) rich in cysteine and glycine for making the hard corneous material of hairs, claws, hooves, horns, and occasionally also scales.
Asunto(s)
Cisteína , Vertebrados , Animales , Cisteína/metabolismo , Vertebrados/metabolismo , Epidermis , Reptiles , Queratinas/genética , Queratinas/metabolismo , Mamíferos/metabolismoRESUMEN
In the developing brain, the phenomenon of neurogenesis is manifested heterotopically, that is, much the same neurogenetic steps occur at different places with a different timetable. This is due apparently to early molecular regionalization of the neural tube wall in the anteroposterior and dorsoventral dimensions, in a checkerboard pattern of more or less deformed quadrangular histogenetic areas. Their respective fate is apparently specified by a locally specific combination of active/repressed genes known as "molecular profile." This leads to position-dependent differential control of proliferation, neurogenesis, differentiation, and other aspects, eventually in a heterochronic manner across adjacent areal units with sufficiently different molecular profiles. It is not known how fixed these heterochronic patterns are. We reexamined here comparatively early patterns of forebrain and hindbrain neurogenesis in a lizard (Lacerta gallotia galloti), a bird (the chick), and a mammal (the rat), as demonstrated by activation of acetylcholinesterase (AChE). This is an early marker of postmitotic neurons, which leaves unlabeled the neuroepithelial ventricular cells, so that we can examine cleared wholemounts of the reacted brains to have a birds-eye view of the emergent neuronal pattern at each stage. There is overall heterochrony between the basal and alar plates of the brain, a known fact, but, remarkably, heterochrony occurs even within the precocious basal plate among its final anteroposterior neuromeric subdivisions and their internal microzonal subdivisions. Some neuromeric units or microzones are precocious, while others follow suit without any specific spatial order or gradient; other similar neuromeric units remain retarded in the midst of quite advanced neighbors, though they do produce similar neurogenetic patterns at later stages. It was found that some details of such neuromeric heterochrony are species-specific, possibly related to differential morphogenetic properties. Given the molecular causal underpinning of the updated prosomeric model used here for interpretation, we comment on the close correlation between some genetic patterns and the observed AChE differentiation patterns.
Asunto(s)
Acetilcolinesterasa , Lagartos , Animales , Pollos , Mamíferos , Neuronas/fisiología , Prosencéfalo , Ratas , RombencéfaloRESUMEN
The author previously worked extensively on the broad problem of the evolution of the vertebrate pallium. He proposed various Bauplan models covering at least gnathostomes, based in the definition of a set of pallial sectors with topologically invariant positional relationships and distinct molecular profiles. Out of one of these models, presented as the "updated tetrapartite pallium model," a modified definition of the earlier lateral pallium sector (LPall) concept emerged, characterizing it in mammals as an unitary claustro-insular transitional (mesocortical) complex intercalated between the neocortex or dorsal pallium (DPall) above and olfactory cortex or ventral pallium (VPall) underneath. A distinctive molecular marker of the early-born deep claustral component of the LPall was found to be the transcription factor Nr4a2, which is not expressed significantly in the overlying insular cortex or in adjoining cortical territories. Given that earlier comparative studies had identified molecularly and topologically comparable VPall, LPall, and DPall sectors in the avian pallium, an avian Nr4a2 probe was applied, aiming to identify the reportedly absent avian claustro-insular complex. An early-born superficial subpopulation of the avian LPall that expresses this marker selectively through development was indeed found. This was proposed to be a claustrum homolog, whereas the remaining Nr4a2-negative avian LPall cells were assumed to represent a possible insular homolog. This last notion was subsequently supported by comparable selective expression of the mouse insular marker Cyp26b, also found restricted to the avian LPall. Some published data suggested that similar molecular properties and structure apply at the reptilian LPall. This analysis was reviewed in Puelles et al. [The pallium in reptiles and birds in the light of the updated tetrapartite pallium model. 2017]. Four years on, the present commentary discusses some international publications accrued in the interval that touch on the claustro-insular homology hypothesis. Some of them are opposed to the hypothesis whereas others corroborate or support it. This raises a number of secondary issues of general interest.
Asunto(s)
Aves , Reptiles , Animales , Aves/anatomía & histología , Mamíferos/anatomía & histología , Ratones , Reptiles/anatomía & histología , Factores de TranscripciónRESUMEN
Here, we review the development, morphology, genes, and proteins of claws in reptiles. Claws likely form owing to the inductive influence of phalangeal mesenchyme on the apical epidermis of developing digits, resulting in hyperproliferation and intense protein synthesis in the dorsal epidermis, which forms the unguis. The tip of claws results from prevalent cell proliferation and distal movement along most of the ungueal epidermis in comparison to the ventral surface forming the subunguis. Asymmetrical growth between the unguis and subunguis forces beta-cells from the unguis to rotate into the apical part of the subunguis, sharpening the claw tip. Further sharpening occurs by scratching and mechanical wearing. Ungueal keratinocytes elongate, form an intricate perimeter and cementing junctions, and remain united impeding desquamation. In contrast, thin keratinocytes in the subunguis form a smooth perimeter, accumulate less corneous beta proteins (CBPs) and cysteine-poor intermediate filament (IF)-keratins, and desquamate. In addition to prevalent glycine-cysteine-tyrosine rich CBPs, special cysteine-rich IF-keratins are also synthesized in the claw, generating numerous SS bonds that harden the thick and compact corneous material. Desquamation and mechanical wear at the tip ensure that the unguis curvature remains approximately stable over time. Reptilian claws are likely very ancient in evolution, although the unguis differentiated like the outer scale surface of scales, while the subunguis might have derived from the inner scale surface. The few hair-like IF-keratins synthesized in reptilian claws indicate that ancestors of sauropsids and mammals shared cysteine-rich IF-keratins. However, the number of these keratins remained low in reptiles, while new types of CBPs function to strengthen claws.
Asunto(s)
Evolución Biológica , Diferenciación Celular/fisiología , Pezuñas y Garras/anatomía & histología , Reptiles/anatomía & histología , Animales , Epidermis/metabolismo , Pezuñas y Garras/crecimiento & desarrollo , Pezuñas y Garras/metabolismo , Queratinocitos/metabolismo , Queratinas/metabolismo , Reptiles/crecimiento & desarrollo , Reptiles/metabolismoRESUMEN
The present review hypothesizes that during the transition from water to land, amniotes lost part of the genetic program for metamorphosis utilized in larvae of their amphibian ancestors, a program that in extant fish and amphibians allows organ regeneration. The direct development of amniotes, with their growth from embryos to adults, occurred with the elimination of larval stages, increases the efficiency of immune responses and the complexity of nervous circuits. In amniotes, T-cells and macrophages likely eliminate embryonic-larval antigens that are replaced with the definitive antigens of adult organs. Among lepidosaurians numerous lizard families during the Permian and Triassic evolved the process of tail autotomy to escape predation, followed by tail regeneration. Autotomy limits inflammation allowing the formation of a regenerative blastema rich in the immunosuppressant and hygroscopic hyaluronic acid. Expression loss of developmental genes for metamorphosis and segmentation in addition to an effective immune system, determined an imperfect regeneration of the tail. Genes involved in somitogenesis were likely lost or are inactivated and the axial skeleton and muscles of the original tail are replaced with a nonsegmented cartilaginous tube and segmental myotomes. Lack of neural genes, negative influence of immune system, and isolation of the regenerating spinal cord within the cartilaginous tube impede the production of nerve and glial cells, and a stratified spinal cord with ganglia. Tissue and organ regeneration in other body regions of lizards and other reptiles is relatively limited, like in the other amniotes, although the cartilage shows a higher regenerative capability than in mammals.
Asunto(s)
Evolución Biológica , Lagartos/fisiología , Regeneración/fisiología , Cola (estructura animal)/fisiología , Animales , Lagartos/genética , Regeneración/genéticaRESUMEN
BACKGROUND: Sex-determining systems may profoundly influence the ecology, behaviour and demography of animals, yet these relationships are poorly understood. Here we investigate whether species with temperature-dependent (TSD) and genetic sex determination (GSD) differ in key demographic traits, using data from 181 species representing all major phylogenetic lineages of extant reptiles. RESULTS: We show that species with TSD exhibit significantly higher within-species variance in sex ratios than GSD species in three major life stages: birth or hatching, juvenility and adulthood. In contrast, sex differences in adult mortality rates do not differ between GSD and TSD species. However, TSD species exhibit significantly greater sex differences in maturation ages than GSD species. CONCLUSION: These results support the recent theoretical model that evolution of TSD is facilitated by sex-specific fitness benefits of developmental temperatures due to bimaturism. Our findings suggest that different sex-determination systems are associated with different demographic characteristics that may influence population viability and social evolution.
Asunto(s)
Reptiles/genética , Procesos de Determinación del Sexo/genética , Razón de Masculinidad , Temperatura , Animales , Teorema de Bayes , Femenino , Masculino , Filogenia , Diferenciación Sexual , Especificidad de la EspecieRESUMEN
Cancer is a threat to multicellular organisms, yet the molecular evolution of pathways that prevent the accumulation of genetic damage has been largely unexplored. The p53 network regulates how cells respond to DNA-damaging stressors. We know little about p53 network molecular evolution as a whole. In this study, we performed comparative genetic analyses of the p53 network to quantify the number of genes within the network that are rapidly evolving and constrained, and the association between lifespan and the patterns of evolution. Based on our previous published data set, we used genomes and transcriptomes of 34 sauropsids and 32 mammals to analyze the molecular evolution of 45 genes within the p53 network. We found that genes in the network exhibited evidence of positive selection and divergent molecular evolution in mammals and sauropsids. Specifically, we found more evidence of positive selection in sauropsids than mammals, indicating that sauropsids have different targets of selection. In sauropsids, more genes upstream in the network exhibited positive selection, and this observation is driven by positive selection in squamates, which is consistent with previous work showing rapid divergence and adaptation of metabolic and stress pathways in this group. Finally, we identified a negative correlation between maximum lifespan and the number of genes with evidence of divergent molecular evolution, indicating that species with longer lifespans likely experienced less variation in selection across the network. In summary, our study offers evidence that comparative genomic approaches can provide insights into how molecular networks have evolved across diverse species.
Asunto(s)
Evolución Molecular , Genes p53 , Selección Genética , Vertebrados/genética , Animales , FilogeniaRESUMEN
In all amniotes specialized intermediate filament keratins (IF-keratins), in addition to keratin-associated and corneous proteins form the outermost cornified layer of the epidermis. Only in reptiles and birds (sauropsids) the epidermis of scales, claws, beaks, and feathers, largely comprises small proteins formerly indicated as "beta-keratins" but here identified as corneous beta-proteins (CBPs) to avoid confusion with true keratins. Genes coding for CBPs have evolved within the epidermal differentiation complex (EDC), a locus with no relationship with those of IF-keratins. CBP genes have the same exon-intron structure as EDC genes encoding other corneous proteins of sauropsids and mammals, but they are unique by encoding a peculiar internal amino acid sequence motif beta-sheet region that allows formation of CBP filaments in the epidermis and epidermal appendages of reptiles and birds. In contrast, skin appendages of mammals, like hairs, claws, horns and nails, contain keratin-associated proteins that, like IF-keratin genes, are encoded by genes in loci different from the EDC. Phylogenetic analysis shows that lepidosaurian (lizards and snakes) and nonlepidosaurian (crocodilians, birds, and turtles) CBPs form two separate clades that likely originated after the divergence of these groups of sauropsids in the Permian Period. Clade-specific CBPs evolved to make most of the corneous material of feathers in birds and of the shell in turtles. Based on the recent identification of the complete sets of CBPs in all major phylogenetic clades of sauropsids, this review provides a comprehensive overview of the molecular evolution of CBPs.
Asunto(s)
Evolución Biológica , Aves/metabolismo , Epidermis/metabolismo , Reptiles/metabolismo , beta-Queratinas/metabolismo , Animales , Aves/genética , Regulación de la Expresión Génica , Reptiles/genética , beta-Queratinas/genéticaRESUMEN
Recent palaeontological data and novel physiological hypotheses now allow a timescaled reconstruction of the evolution of endothermy in birds and mammals. A three-phase iterative model describing how endothermy evolved from Permian ectothermic ancestors is presented. In Phase One I propose that the elevation of endothermy - increased metabolism and body temperature (Tb ) - complemented large-body-size homeothermy during the Permian and Triassic in response to the fitness benefits of enhanced embryo development (parental care) and the activity demands of conquering dry land. I propose that Phase Two commenced in the Late Triassic and Jurassic and was marked by extreme body-size miniaturization, the evolution of enhanced body insulation (fur and feathers), increased brain size, thermoregulatory control, and increased ecomorphological diversity. I suggest that Phase Three occurred during the Cretaceous and Cenozoic and involved endothermic pulses associated with the evolution of muscle-powered flapping flight in birds, terrestrial cursoriality in mammals, and climate adaptation in response to Late Cenozoic cooling in both birds and mammals. Although the triphasic model argues for an iterative evolution of endothermy in pulses throughout the Mesozoic and Cenozoic, it is also argued that endothermy was potentially abandoned at any time that a bird or mammal did not rely upon its thermal benefits for parental care or breeding success. The abandonment would have taken the form of either hibernation or daily torpor as observed in extant endotherms. Thus torpor and hibernation are argued to be as ancient as the origins of endothermy itself, a plesiomorphic characteristic observed today in many small birds and mammals.
Asunto(s)
Evolución Biológica , Aves/clasificación , Aves/fisiología , Regulación de la Temperatura Corporal/fisiología , Mamíferos/clasificación , Mamíferos/fisiología , Adaptación Fisiológica/fisiología , AnimalesRESUMEN
During land adaptation of the integument in tetrapods, an efficient stratum corneum was originated through the evolution of numerous corneous proteins in addition to the framework of intermediate filament-keratins present in keratinocytes. The new genes for corneous proteins were originated in a chromosome region indicated as epidermal differentiation complex (EDC), a locus with no apparent relationship to keratin genes. The addition of EDC proteins to IF-keratins transformed the process of epidermal keratinization present in anamniotes into a new process of cornification in the epidermis and skin appendages of amniotes, including hairs and feathers. In sauropsids among other EDC proteins a peculiar type of small proteins evolved a central region of 34 amino acids conformed as beta-sheets that, differently from the other EDC proteins, allowed the formation of long polymers of filamentous proteins customarily termed beta-keratins but in the present review reclassified as EDC corneous beta proteins. To the initial beta-sheets present in the corneous beta proteins specific N- and C-regions were later added in the proteins of different sauropsids in relation to the evolution of the corneous layer and skin appendages. Cornification contributed to the evolutive success of amniotes in the terrestrial environment.
Asunto(s)
Epidermis/metabolismo , Queratinas/metabolismo , Vertebrados/metabolismo , Amnios/metabolismo , Animales , Evolución Biológica , Queratinas/química , Estructura Secundaria de ProteínaRESUMEN
Prototype galectins, endogenously expressed animal lectins with a single carbohydrate recognition domain, are well-known regulators of tissue properties such as growth and adhesion. The earliest discovered and best studied of the prototype galectins is Galectin-1 (Gal-1). In the Gallus gallus (chicken) genome, Gal-1 is represented by two homologs: Gal-1A and Gal-1B, with distinct biochemical properties, tissue expression, and developmental functions. We investigated the origin of the Gal-1A/Gal-1B divergence to gain insight into when their developmental functions originated and how they could have contributed to vertebrate phenotypic evolution. Sequence alignment and phylogenetic tree construction showed that the Gal-1A/Gal-1B divergence can be traced back to the origin of the sauropsid lineage (consisting of extinct and extant reptiles and birds) although lineage-specific duplications also occurred in the amphibian and actinopterygian genomes. Gene synteny analysis showed that sauropsid gal-1b (the gene for Gal-1B) and its frog and actinopterygian gal-1 homologs share a similar chromosomal location, whereas sauropsid gal-1a has translocated to a new position. Surprisingly, we found that chicken Gal-1A, encoded by the translocated gal-1a, was more similar in its tertiary folding pattern than Gal-1B, encoded by the untranslocated gal-1b, to experimentally determined and predicted folds of nonsauropsid Gal-1s. This inference is consistent with our finding of a lower proportion of conserved residues in sauropsid Gal-1Bs, and evidence for positive selection of sauropsid gal-1b, but not gal-1a genes. We propose that the duplication and structural divergence of Gal-1B away from Gal-1A led to specialization in both expression and function in the sauropsid lineage.
Asunto(s)
Galectinas/química , Vertebrados/clasificación , Animales , Galectinas/genética , Filogenia , Estructura Secundaria de Proteína , Vertebrados/genéticaRESUMEN
Sequencing of vertebrate genomes permits changes in distinct protein families, including gene gains and losses, to be ascribed to lineage-specific phenotypes. A prominent example of this is the large-scale duplication of beta-keratin genes in the ancestors of birds, which was crucial to the subsequent evolution of their beaks, claws, and feathers. Evidence suggests that the shell of Pseudomys nelsoni contains at least 16 beta-keratins proteins, but it is unknown whether this is a complete set and whether their corresponding genes are orthologous to avian beak, claw, or feather beta-keratin genes. To address these issues and to better understand the evolution of the turtle shell at a molecular level, we surveyed the diversity of beta-keratin genes from the genome assemblies of three turtles, Chrysemys picta, Pelodiscus sinensis, and Chelonia mydas, which together represent over 160 Myr of chelonian evolution. For these three turtles, we found 200 beta-keratins, which indicate that, as for birds, a large expansion of beta-keratin genes in turtles occurred concomitantly with the evolution of a unique phenotype, namely, their plastron and carapace. Phylogenetic reconstruction of beta-keratin gene evolution suggests that separate waves of gene duplication within a single genomic location gave rise to scales, claws, and feathers in birds, and independently the scutes of the shell in turtles.