Tetrapod Lineage Research Articles

Comparative functional morphology indicates niche partitioning among sympatric marine reptiles.

Mesozoic marine ecosystems were dominated by diverse lineages of aquatic tetrapods. For over 50 Ma in the Jurassic until the Early Cretaceous, plesiosaurians, ichthyosaurians and thalattosuchian crocodylomorphs coexisted at the top levels of trophic food webs. We created a functional dataset of continuous craniomandibular and dental characters known from neontological studies to be functionally significant in modern aquatic tetrapods. We analysed this dataset with multivariate ordination and inferential statistics to assess functional similarities and differences in the marine reptile faunas of two well-sampled Jurassic ecosystems deposited in the same seaway: the Oxford Clay Formation (OCF, Callovian-early Oxfordian, Middle-Late Jurassic) and the Kimmeridge Clay Formation (KCF, Kimmeridgian-Tithonian, Late Jurassic) of the UK. Lower jaw-based macroevolutionary trends are similar to those of tooth-based diversity studies. Closely related species cluster together, with minimal overlaps in the morphospace. Marine reptile lineages were characterized by the distinctive combinations of features, but we reveal multiple instances of morphofunctional convergence among different groups. We quantitatively corroborate previous observations that the ecosystems in the OCF and KCF were markedly distinct in faunal composition and structure. Morphofunctional differentiation may have enabled specialization and was an important factor facilitating the coexistence of diverse marine reptile assemblages in deep time.

Beakiation: how a novel parrot gait expands the locomotor repertoire of living birds.

Occupation of arboreal habitats poses myriad locomotor challenges, driving both anatomical and behavioural innovations across various tetrapod lineages. Here, we report and biomechanically assess a novel, beak-driven locomotor mode-'beakiation'-by which parrots advance along the underside of narrow arboreal substrates. Using high-speed videography and kinetic analyses, we describe the limb loading patterns and pendular mechanics of beakiation, and compare the biomechanical characteristics of this gait with other suspensory behaviours (namely, forelimb-driven brachiation and inverted quadrupedal walking). We report that the parrot beak experiences comparable force magnitudes (approx. 150% body weight in the normal plane; approx. 50% body weight in the fore-aft plane) to the forelimbs of brachiating primates. Parrot beakiation is also characterized by longer-than-expected pendular periods, similar to observations of gibbon brachiation. However, in terms of mechanical energy recovery, beakiation is typified by lower levels of energetic recovery than brachiating specialists: a product of its slower, more careful nature. The observation of this novel behaviour-which adds to a growing base of literature regarding beak-assisted locomotor strategies in birds-highlights the extraordinary behavioural plasticity of birds, the functional versatility of the avian beak, and the difficulties in reconstructing an animal's locomotor repertoire from morphological characteristics alone.

Morphological description of spontaneous pelvic fin loss in a neotropical cichlid fish.

Pelvic finsare a characteristic structure of the vertebrate Bauplan. Yet, pelvic fin loss has occurred repeatedly across a wide diversity of other lineages of tetrapods and at least 48 times in teleost fishes. This pelvic finless condition is often associated with other morphological features such as body elongation, loss of additional structures, and bilateral asymmetry. However, despite the remarkable diversity in the several thousand cichlid fish species, none of them are characterized by the complete absence of pelvic fins. Here, we examined the musculoskeletal structure and associated bilateral asymmetry in Midas cichlids (Amphilophus cf. citrinellus) that lost their pelvic fins spontaneously in the laboratory. Due to this apparent mutational loss of the pelvic girdle and fins, the external and internal anatomy are described in a series of "normal" Midas individuals and their pelvic finless sibling tankmates. First, other traits associated with teleost pelvic fin loss, the genetic basis of pelvic fin loss, and the potential for pleiotropic effects of these genes on other traits in teleosts were all reviewed. Using these traits as a guide, we investigated whether other morphological differences were associated with the pelvic girdle/fin loss. The mean values of the masses of muscle of the pectoral fin, fin ray numbers in the unpaired fins, and oral jaw tooth numbers did not differ between the two pelvic fin morphotypes. However, significant differences in meristic values of the paired traits assessed were observed for the same side of the body between morphotypes. Notably, bilateral asymmetry was found exclusively for the posterior lateral line scales. Finally, we found limited evidence of pleiotropic effects, such as lateral line scale numbers and fluctuating asymmetry between the Midas pelvic fin morphotypes. The fast and relatively isolated changes in the Midas cichlids suggest minor but interesting pleiotropic effects could accompany loss of cichlid pelvic fins.

Coronary artery established through amniote evolution.

Coronary arteries are a critical part of the vascular system and provide nourishment to the heart. In humans, even minor defects in coronary arteries can be lethal, emphasizing their importance for survival. However, some teleosts survive without coronary arteries, suggesting that there may have been some evolutionary changes in the morphology and function of coronary arteries in the tetrapod lineage. Here, we propose that the true ventricular coronary arteries were newly established during amniote evolution through remodeling of the ancestral coronary vasculature. In mouse (Mus musculus) and Japanese quail (Coturnix japonica) embryos, the coronary arteries unique to amniotes are established by the reconstitution of transient vascular plexuses: aortic subepicardial vessels (ASVs) in the outflow tract and the primitive coronary plexus on the ventricle. In contrast, amphibians (Hyla japonica, Lithobates catesbeianus, Xenopus laevis, and Cynops pyrrhogaster) retain the ASV-like vasculature as truncal coronary arteries throughout their lives and have no primitive coronary plexus. The anatomy and development of zebrafish (Danio rerio) and chondrichthyans suggest that their hypobranchial arteries are ASV-like structures serving as the root of the coronary vasculature throughout their lives. Thus, the ventricular coronary artery of adult amniotes is a novel structure that has acquired a new remodeling process, while the ASVs, which occur transiently during embryonic development, are remnants of the ancestral coronary vessels. This evolutionary change may be related to the modification of branchial arteries, indicating considerable morphological changes underlying the physiological transition during amniote evolution.

Body size and life history shape the historical biogeography of tetrapods.

Dispersal across biogeographic barriers is a key process determining global patterns of biodiversity as it allows lineages to colonize and diversify in new realms. Here we demonstrate that past biogeographic dispersal events often depended on species' traits, by analysing 7,009 tetrapod species in 56 clades. Biogeographic models incorporating body size or life history accrued more statistical support than trait-independent models in 91% of clades. In these clades, dispersal rates increased by 28-32% for lineages with traits favouring successful biogeographic dispersal. Differences between clades in the effect magnitude of life history on dispersal rates are linked to the strength and type of biogeographic barriers and intra-clade trait variability. In many cases, large body sizes and fast life histories facilitate dispersal success. However, species with small bodies and/or slow life histories, or those with average traits, have an advantage in a minority of clades. Body size-dispersal relationships were related to a clade's average body size and life history strategy. These results provide important new insight into how traits have shaped the historical biogeography of tetrapod lineages and may impact present-day and future biogeographic dispersal.

A functional framework for interpreting phalangeal form.

Across tetrapods, the proportional lengths of the manual and pedal phalanges are highly constrained, following a generalized blueprint of shortening in a proximodistal gradient. Despite this, several lineages of both mammals (e.g. sloths, bats and colugos) and birds (e.g. raptors, parrots and woodpeckers) have broken this pattern, shortening the proximal phalanx while elongating more distal elements. As yet, no unifying explanation for this convergence has been empirically evaluated. This study combines a comparative phylogenetic assessment of phalangeal morphology across mammals and birds with a novel bioinspired robotics approach to explicitly test functional hypotheses relating to these morphotypes. We demonstrate that shortening the proximal phalanx allows taxa to maximize forces produced at the proximal interphalangeal joint, while elongation of subsequent elements maintains total ray length-ensuring arboreal species can still enclose large-diameter supports. Within suspensory and vertically clinging mammals, we additionally observe a secondary adaptation towards maximizing grip strength: namely increasing the height of the trochleae to increase the moment arm of digital flexor muscles that cross the joint. Together, our analyses highlight that numerous tetrapod lineages independently converged upon this morphotype to maximize proximal gripping strength, an adaptation to support specialized hunting and locomotor behaviours.

MHC architecture in amphibians - ancestral reconstruction, gene rearrangements and duplication patterns.

The hypervariable major histocompatibility complex (MHC) is a crucial component of vertebrate adaptive immunity, but large-scale studies on MHC macroevolution in non-model vertebrates have long been constrained by methodological limitations. Here, we used rapidly accumulating genomic data to reconstruct macroevolution of the MHC region in amphibians. We retrieved contigs containing the MHC region from genome assemblies of 32 amphibian species and examined major structural rearrangements, duplication patterns and gene structure across the amphibian phylogeny. Based on the few available caecilian and urodele genomes we showed that the structure of ancestral MHC region in amphibians was probably relatively simple and compact, with a close physical linkage between MHC-I and MHC-II regions. This ancestral MHC architecture was generally conserved in anurans, although the evolution of class I subregion proceeded towards more extensive duplication and rapid expansion of gene copy number, providing evidence for dynamic evolutionary trajectories. Although in anurans we recorded tandems of duplicated MHC-I genes outside the core subregion, our phylogenetic analyses of MHC-I sequences provided little support for an expansion of nonclassical MHC-Ib genes across amphibian families. Finally, we found that intronic regions of amphibian classical MHC genes were much longer when compared to other tetrapod lineages (birds and mammals), which could partly be driven by the expansion of genome size. Our study reveals novel evolutionary patterns of the MHC region in amphibians and provides a comprehensive framework for further studies on the MHC macroevolution across vertebrates.

A new long-necked archosauromorph from the Guanling Formation (Anisian, Middle Triassic) of southwestern China and its implications for neck evolution in tanystropheids.

A long neck is an evolutionary innovation convergently appearing in multiple tetrapod lineages, including groups of plesiosaurs, non-archosauriform archosauromorphs, turtles, sauropodomorphs, birds, and mammals. Among all tetrapods both extant and extinct, two Triassic archosauromorphs, Tanystropheus and Dinocephalosaurus, have necks that are particularly elongated relative to the lengths of their trunks. However, the evolutionary history of such hyper-elongated necks in these two archosauromorph clades remains unknown, partially because known close relatives such as Macrocnemus and Pectodens possess only moderately elongated necks. Here, we describe a newly discovered early diverging archosauromorph, Gracilicollum latens gen. et sp. nov., based on a specimen comprising a partial neck and an incompletely preserved skull. The long neck is composed of at least 18 cervical vertebrae. The dentition suggests that this new taxon most likely represents an aquatic piscivore, similar to Dinocephalosaurus and Tanystropheus hydroides. Despite possessing a high number of cervical vertebrae, Gracilicollum gen. nov. is recovered as a tanystropheid in an evolutionary grade between Macrocnemus and Tanystropheus rather than as a close relative of Dinocephalosaurus, a result that is primarily attributable to the presence of palatal teeth and the anatomy of the cervical vertebrae in Gracilicollum gen. nov. Considering the information provided by the new specimen, we provide a detailed discussion of the cervical evolution in dinocephalosaurids and tanystropheids, which is shown to be highly complex and mosaic in nature.

A new Carboniferous edaphosaurid and the origin of herbivory in mammal forerunners

Herbivory evolved independently in several tetrapod lineages during the Late Carboniferous and became more widespread throughout the Permian Period, eventually leading to the basic structure of modern terrestrial ecosystems. Here we report a new taxon of edaphosaurid synapsid based on two fossils recovered from the Moscovian-age cannel coal of Linton, Ohio, which we interpret as an omnivore–low-fibre herbivore. Melanedaphodon hovaneci gen. et sp. nov. provides the earliest record of an edaphosaurid to date and is one of the oldest known synapsids. Using high-resolution X-ray micro-computed tomography, we provide a comprehensive description of the new taxon that reveals similarities between Late Carboniferous and early Permian (Cisuralian) members of Edaphosauridae. The presence of large bulbous, cusped, marginal teeth alongside a moderately-developed palatal battery, distinguishes Melanedaphodon from all other known species of Edaphosauridae and suggests adaptations for processing tough plant material already appeared among the earliest synapsids. Furthermore, we propose that durophagy may have provided an early pathway to exploit plant resources in terrestrial ecosystems.

Evolutionary and Genomic Diversity of True Polyploidy in Tetrapods.

True polyploid organisms have more than two chromosome sets in their somatic and germline cells. Polyploidy is a major evolutionary force and has played a significant role in the early genomic evolution of plants, different invertebrate taxa, chordates, and teleosts. However, the contribution of polyploidy to the generation of new genomic, ecological, and species diversity in tetrapods has traditionally been underestimated. Indeed, polyploidy represents an important pathway of genomic evolution, occurring in most higher-taxa tetrapods and displaying a variety of different forms, genomic configurations, and biological implications. Herein, we report and discuss the available information on the different origins and evolutionary and ecological significance of true polyploidy in tetrapods. Among the main tetrapod lineages, modern amphibians have an unparalleled diversity of polyploids and, until recently, they were considered to be the only vertebrates with closely related diploid and polyploid bisexual species or populations. In reptiles, polyploidy was thought to be restricted to squamates and associated with parthenogenesis. In birds and mammals, true polyploidy has generally been considered absent (non-tolerated). These views are being changed due to an accumulation of new data, and the impact as well as the different evolutionary and ecological implications of polyploidy in tetrapods, deserve a broader evaluation.

The role of cranial osteoderms on the mechanics of the skull in scincid lizards.

Osteoderms (ODs) are calcified organs formed directly within the skin of most major extant tetrapod lineages. Lizards possibly show the greatest diversity in ODs morphology and distribution. ODs are commonly hypothesized to function as a defensive armor. Here we tested the hypothesis that cranial osteoderms also contribute to the mechanics of the skull during biting. A series of in vivo experiments were carried out on three specimens of Tiliqua gigas. Animals were induced to bite a force plate while a single cranial OD was strain gauged. A finite element (FE) model of a related species, Tiliqua scincoides, was developed and used to estimate the level of strain across the same OD as instrumented in the in vivo experiments. FE results were compared to the in vivo data and the FE model was modified to test two hypothetical scenarios in which all ODs were (i) removed from, and (ii) fused to, the skull. In vivo data demonstrated that the ODs were carrying load during biting. The hypothetical FE models showed that when cranial ODs were fused to the skull, the overall strain across the skull arising from biting was reduced. Removing the ODs showed an opposite effect. In summary, our findings suggest that cranial ODs contribute to the mechanics of the skull, even when they are loosely attached.

IL-10 Negatively Controls the Primary T Cell Response of Tilapia by Triggering the JAK1/STAT3/SOCS3 Axis That Suppresses NF-κB and MAPK/ERK Signaling.

The braking mechanisms to protect the host from tissue damage and inflammatory disease caused by an overexuberant immune response are common in many T cell subsets. However, the negative regulation of T cell responses and detailed mechanisms are not well understood in early vertebrates. In the current study, using a Nile tilapia (Oreochromis niloticus) model, we investigated the suppression of T cell immunity by IL-10. Tilapia encodes an evolutionarily conserved IL-10, whose expression in lymphocytes is markedly induced during the primary adaptive immune response against Aeromonas hydrophila infection. Activated T cells of tilapia produce IL-10, which in turn inhibits proinflammatory cytokine expression and suppresses PHA-induced T cell activation. Moreover, administration of IL-10 impairs the proliferation of tilapia T cells, reduces their potential to differentiate into Th subsets, and cripples the cytotoxic function, rendering the animals more vulnerable to pathogen attack. After binding to its receptor IL-10Ra, IL-10 activates the JAK1/STAT3 axis by phosphorylation and enhances the expression of the suppressor of cytokine signaling 3 (SOCS3), which in turn attenuates the activation of the NF-κB and MAPK/ERK signaling pathways, thus suppressing the T cell response of tilapia. Our findings elucidate a negative regulatory mechanism of T cell immunity in a fish species and support the notion that the braking mechanism of T cells executed through IL-10 existed prior to the divergence of the tetrapod lineage from teleosts. Therefore, this study, to our knowledge, provides a novel perspective on the evolution of the adaptive immune system.

A Long-Running Arms Race between APOBEC1 Genes and Retroviruses in Tetrapods.

Activation-induced cytidine deaminase/apolipoprotein B mRNA editing catalytic polypeptide-like (AID/APOBEC) proteins are cytosine deaminases implicated in diverse biological functions. APOBEC1 (A1) proteins have long been thought to regulate lipid metabolism, whereas the evolutionary significance of A1 proteins in antiviral defense remains largely obscure. Endogenous retroviruses (ERVs) document past retroviral infections and are ubiquitous within the vertebrate genomes. Here, we identify the A1 gene repertoire, characterize the A1-mediated mutation footprints in ERVs, and interrogate the evolutionary arms race between A1 genes and ERVs across vertebrate species. We find that A1 genes are widely present in tetrapods, recurrently amplified and lost in certain lineages, suggesting that A1 genes might have originated during the early evolution of tetrapods. A1-mediated mutation footprints can be detected in ERVs across tetrapods. Moreover, A1 genes appear to have experienced episodic positive selection in many tetrapod lineages. Taken together, we propose that a long-running arms race between A1 genes and retroviruses might have persisted throughout the evolutionary course of tetrapods. IMPORTANCE APOBEC3 (A3) genes have been thought to function in defense against retroviruses, whereas the evolutionary significance of A1 proteins in antiviral defense remains largely obscure. In this study, we identify the A1 gene repertoire, characterize the A1-mediated mutation footprints in endogenous retroviruses (ERVs), and explore the evolutionary arms race between A1 genes and ERVs across vertebrate species. We found A1 proteins originated during the early evolution of tetrapods, and detected the footprints of A1-induced hypermutations in retroviral fossils. A1 genes appear to have experienced pervasive positive selection in tetrapods. Our study indicates a long-running arms race between A1 genes and retroviruses taking place throughout the evolutionary course of tetrapods.

Grouping behavior in a Triassic marine apex predator

Marine tetrapods occupy important roles in modern marine ecosystems and often gather in large aggregations driven by patchy prey distribution,1,2 social or reproductive behaviors,3,4 or oceanographic factors.5 Here, we show that similar grouping behaviors evolved in an early marine tetrapod lineage, documented by dozens of specimens of the giant ichthyosaur Shonisaurus in the Luning Formation in West Union Canyon, Nevada, USA.6,7 A concentration of at least seven skeletons closely preserved on a single bedding plane received the bulk of previous attention. However, many more specimens are preserved across ∼106 square meters and ∼200 stratigraphic meters of outcrop representing an estimated >105-6 years. Unlike other marine-tetrapod-rich deposits, this assemblage is essentially monotaxic; other vertebrate fossils are exceptionally scarce. Large individuals are disproportionately abundant, with the exception of multiple neonatal or embryonic specimens, indicating an unusual demographic composition apparently lacking intermediate-sized juveniles or subadults. Combined with geological evidence, our data suggest that dense aggregations of Shonisaurus inhabited this moderately deep, low-diversity, tropical marine environment for millennia during the latest Carnian Stage of the Late Triassic Period (237-227 Ma). Thus, philopatric grouping behavior in marine tetrapods, potentially linked to reproductive activity, has an antiquity of at least 230 million years.

The influence of substrate size upon pulling and gripping forces in parrots (Psittaciformes: Agapornis roseicollis).

The ability to securely grasp substrates of variable diameter is critical to arboreal animals. Arboreal specialists have emerged across several vertebrate lineages - including mammals, lizards and amphibians - and several attempts have been made to quantify their grasping performance, by measuring either gripping (i.e. forces generated about an object or substrate enclosed within the digits) or pulling (i.e. the ability to resist being removed from a substrate) forces. In this study, we present data on both pulling and gripping performance across a range of substrate diameters (0.5-17.5 mm) within a model parrot species (Agapornis roseicollis). Parrots represent an ancient arboreal lineage, allowing us to compare their abilities with those of arboreal specialists within other tetrapod groups. Data were collected using 3D-printed perches of variable diameter, and forces were registered using either an AMTI low-load force plate (grip force) or a Harvard Apparatus portable strength tester (pull force). Gripping forces peaked at a 5 mm diameter perch, while pulling forces were greatest at a 2.5 mm diameter. All forces strongly diminished above 10 mm size, suggesting grip force is optimized when utilizing small perches, a finding which corresponds to observational studies of preferential perching habits among free-ranging parrots. Relative grasping performance (adjusted for body size) in parrots is roughly equivalent to that of other arboreal specialists from other tetrapod lineages, but low when compared with that of raptorial birds that utilize their feet during aerial prey capture. Further taxonomic sampling is encouraged to contextualize how grasping performance varies in an adaptive evolutionary context.

Synthesis of geological data and comparative phylogeography of lowland tetrapods suggests recent dispersal through lowland portals crossing the Eastern Andean Cordillera.

Vicariance is the simplest explanation for divergence between sister lineages separated by a potential barrier, and the northern Andes would seem to provide an ideal example of a vicariant driver of divergence. We evaluated the potential role of the uplift of the Eastern Cordillera (EC) of the Colombian Andes and the Mérida Andes (MA) of Venezuela as drivers of vicariance between lowland populations co-distributed on both flanks. We synthesized published geological data and provided a new reconstruction showing that the EC-MA grew from north to south, reaching significant heights and separating drainages and changing sediment composition by 38–33 million years ago (Ma). A few lowland passes across the EC-MA may have reached their current heights (~1,900 m a.s.l.) at 3–5 Ma. We created a comparative phylogeographic data set for 37 lineages of lowland tetrapods. Based on molecular phylogenetic analyses, most divergences between sister populations or species across the EC-MA occurred during Pliocene and the Quaternary and a few during the latest Miocene, and coalescent simulations rejected synchronous divergence for most groups. Divergence times were on average slightly but significantly more recent in homeotherms relative to poikilotherms. Because divergence ages are mostly too recent relative to the geological history and too asynchronous relative to each other, divergence across the northern Andes may be better explained by organism-environment interactions concomitant with climate oscillations during the Pleistocene, and/or dispersal across portals through the Andes.

Cephalic salt gland evolution in Mesozoic pelagic crocodylomorphs

Abstract Secondarily marine tetrapod lineages have independently evolved osmoregulatory adaptations for life in salt water but inferring physiological changes in extinct marine tetrapods is difficult. The Mesozoic crocodylomorph clade Thalattosuchia is unique in having both direct evidence from natural endocasts and several proposed osteological correlates for salt exocrine glands. Here, we investigate salt gland evolution in thalattosuchians by creating endocranial reconstructions from CT scans of eight taxa (one basal thalattosuchian, one teleosauroid, two basal metriorhynchoids and four metriorhynchids) and four outgroups (three extant crocodylians and the basal crocodyliform Protosuchus) to identify salt gland osteological correlates. All metriorhynchoids show dorsolateral nasal cavity expansions corresponding to the location of nasal salt glands in natural casts, but smaller expansions in teleosauroids correspond more with the cartilaginous nasal capsule. The different sizes of these expansions suggest the following evolutionary sequence: (1) plesiomorphically small glands present in semi-aquatic teleosauroids draining through the nasal vestibule; (2) moderately sized glands in the basalmost metriorhynchoid Pelagosaurus; and (3) hypertrophied glands in the clade comprising Eoneustes and metriorhynchids, with a pre-orbital fenestra providing a novel exit for salt drainage. The large gland size inferred from basal metriorhynchoids indicates advanced osmoregulation occurred while metriorhynchoids were semi-aquatic. This pattern does not precisely fit into current models of physiological evolution in marine tetrapods and suggests a unique sequence of changes as thalattosuchians transitioned from land to sea.

IL-2 Signaling Couples the MAPK and mTORC1 Axes to Promote T Cell Proliferation and Differentiation in Teleosts.

IL-2 is a pleiotropic cytokine that is critical for T cell immunity. Although the IL-2-mediated regulation of T cell immunity in mammals is relatively well understood, it remains largely unknown whether and how IL-2 regulates T cell immunity in lower vertebrates. To address this knowledge gap, we investigated the role played by IL-2 in the regulation of T cell response, as well as the associated underlying mechanisms in a teleost fish, large yellow croaker (Larimichthys crocea). We found that large yellow croaker (L. crocea) IL-2 (LcIL-2) significantly promoted T cell proliferation both in vivo and in vitro; significantly induced the differentiation of Th1, Th2, regulatory T, and cytotoxic T cells while inhibiting Th17 differentiation; and participated in the elimination of invading pathogenic bacteria. Mechanistically, the binding of LcIL-2 to its heterotrimer receptor complex (LcIL-15Rα/LcIL-2Rβ/Lcγc) triggered the conserved JAK-STAT5 pathway, which in turn regulated the expression of genes involved in T cell expansion, differentiation, and biological function. The MAPK and mammalian target of rapamycin complex 1 (mTORC1) axes, which are involved in TCR-mediated signaling, were also required for LcIL-2-mediated T cell response. Collectively, our results demonstrated that fish IL-2 plays a comprehensive regulatory role in T cell response and highlighted the complex and delicate network regulating T cell-driven immune response. We propose that T cell immunity is regulated by the interplay between TCR signaling and cytokine signaling, and that this basic strategy evolved before the emergence of the tetrapod lineage. Our findings provide valuable insights into the regulatory mechanisms underlying T cell response in teleosts.

Evolution of touch and proprioception of the limbs: Insights from fish and humans.

The function of the hands is inextricably linked to cutaneous mechanosensation, both in touch and in how hand movement and posture (proprioception) are controlled. The structure and behavior of hands and distal forelimbs of other vertebrates have been evolutionarily shaped by these mechanosensory functions. The distal forelimb of tetrapod vertebrates is homologous to the pectoral fin rays and membrane of fishes. Fish fins demonstrate similar mechanosensory abilities to hands and other distal tetrapod forelimbs in touch and proprioception. These results indicate that vertebrates were using the core mechanosensory inputs, such as fast adapting and slow adapting nerve responses, to inform fin and limb function and behavior before their diversification in fish and tetrapod lineages.

Analysis of the mast cell expressed carboxypeptidase A3 and its structural and evolutionary relationship to other vertebrate carboxypeptidases

Metallo-carboxypeptidases are exopeptidases with diverse expression and function, found in all kingdoms of life from bacteria to mammals. One of them, the carboxypeptidase A3 (CPA3), has become an important component of the mammalian immune system by its expression in mast cells. Mast cells (MCs) are highly specialized sentinel cells, which store large amounts of bioactive mediators, including CPA3, in very abundant cytoplasmic granules. Clinical studies have found an increased CPA3 expression in asthma but the physiological role as well as the evolutionary origin of CPA3 remains largely unexplored. CPA3 belongs to the M14A subfamily of metallo-carboxypeptidases, which among others also includes the digestive enzymes CPA1, CPA2, CPB1 and CPO. To study the appearance of CPA3 during vertebrate evolution, we here performed bioinformatic analyses of homologous genes and gene loci from a broad panel of metazoan animals from invertebrates to mammals. The phylogenetic analysis indicated that CPA3 appeared at the base of tetrapod evolution in a branch closer to CPB1 than to other CPAs. Indeed, CPA3 and CPB1 are also located in the same locus, on chromosome 3 in humans. The presence of CPA3 only in tetrapods and not in fishes, suggested that CPA3 could have appeared by a gene duplication from CPB1 during early tetrapod evolution. However, the apparent loss of CPA3 in several tetrapod lineages, e.g. in birds and monotremes, indicates a complex evolution of the CPA3 gene. Interestingly, in the lack of CPA3 in fishes, zebrafish MCs express instead CPA5 for which the most closely related human carboxypeptidase is CPA1, which has a similar cleavage specificity as CPA3. Collectively, these findings clarify and add to our understanding of the evolution of hematopoietic proteases expressed by mast cells.