Gene Classification Based on Amino Acid Motifs and Residues: The DLX (distal-less) Test Case

BACKGROUND:Comparative studies using hundreds of sequences can give a detailed picture of the evolution of a given gene family. Nevertheless, retrieving only the sequences of interest from public databases can be difficult, in particular, when working with highly divergent sequences. The difficulty increases substantially when one wants to include in the study sequences from many (or less well studied) species whose genomes are non-annotated or incompletely annotated. METHODOLOGY/PRINCIPAL FINDINGS:In this work we evaluate the usefulness of different approaches of gene retrieval and classification, using the distal-less (DLX) gene family as a test case. Furthermore, we evaluate whether the use of a large number of gene sequences from a wide range of animal species, the use of multiple alternative alignments, and the use of amino acids aligned with high confidence only, is enough to recover the accepted DLX evolutionary history. CONCLUSIONS/SIGNIFICANCE:The canonical DLX homeobox gene sequence here derived, together with the characteristic amino acid variants here identified in the DLX homeodomain region, can be used to retrieve and classify DLX genes in a simple and efficient way. A program is made available that allows the easy retrieval of synteny information that can be used to classify gene sequences. Maximum likelihood trees using hundreds of sequences can be used for gene identification. Nevertheless, for the DLX case, the proposed DLX evolutionary is not recovered even when multiple alignment algorithms are used

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Genomic Organization and Expression Demonstrate Spatial and Temporal Hox Gene Colinearity in the Lophotrochozoan Capitella sp. I

Hox genes define regional identities along the anterior–posterior axis in many animals. In a number of species, Hox genes are clustered in the genome, and the relative order of genes corresponds with position of expression in the body. Previous Hox gene studies in lophotrochozoans have reported expression for only a subset of the Hox gene complement and/or lack detailed genomic organization information, limiting interpretations of spatial and temporal colinearity in this diverse animal clade. We studied expression and genomic organization of the single Hox gene complement in the segmented polychaete annelid Capitella sp. I. Total genome searches identified 11 Hox genes in Capitella, representing 11 distinct paralog groups thought to represent the ancestral lophotrochozoan complement. At least 8 of the 11 Capitella Hox genes are genomically linked in a single cluster, have the same transcriptional orientation, and lack interspersed non-Hox genes. Studying their expression by situ hybridization, we find that the 11 Capitella Hox genes generally exhibit spatial and temporal colinearity. With the exception of CapI-Post1, Capitella Hox genes are all expressed in broad ectodermal domains during larval development, consistent with providing positional information along the anterior–posterior axis. The anterior genes CapI-lab, CapI-pb, and CapI-Hox3 initiate expression prior to the appearance of segments, while more posterior genes appear at or soon after segments appear. Many of the Capitella Hox genes have either an anterior or posterior expression boundary coinciding with the thoracic–abdomen transition, a major body tagma boundary. Following metamorphosis, several expression patterns change, including appearance of distinct posterior boundaries and restriction to the central nervous system. Capitella Hox genes have maintained a clustered organization, are expressed in the canonical anterior–posterior order found in other metazoans, and exhibit spatial and temporal colinearity, reflecting Hox gene characteristics that likely existed in the protostome–deuterostome ancestor

A general scenario of Hox gene inventory variation among major sarcopterygian lineages

<p>Abstract</p> <p>Background</p> <p><it>H</it>ox genes are known to play a key role in shaping the body plan of metazoans. Evolutionary dynamics of these genes is therefore essential in explaining patterns of evolutionary diversity. Among extant sarcopterygians comprising both lobe-finned fishes and tetrapods, our knowledge of the <it>Hox </it>genes and clusters has largely been restricted in several model organisms such as frogs, birds and mammals. Some evolutionary gaps still exist, especially for those groups with derived body morphology or occupying key positions on the tree of life, hindering our understanding of how <it>Hox </it>gene inventory varied along the sarcopterygian lineage.</p> <p>Results</p> <p>We determined the <it>Hox </it>gene inventory for six sarcopterygian groups: lungfishes, caecilians, salamanders, snakes, turtles and crocodiles by comprehensive PCR survey and genome walking. Variable <it>Hox </it>genes in each of the six sarcopterygian group representatives, compared to the human <it>Hox </it>gene inventory, were further validated for their presence/absence by PCR survey in a number of related species representing a broad evolutionary coverage of the group. Turtles, crocodiles, birds and placental mammals possess the same 39 <it>Hox </it>genes. <it>HoxD12 </it>is absent in snakes, amphibians and probably lungfishes. <it>HoxB13 </it>is lost in frogs and caecilians. Lobe-finned fishes, amphibians and squamate reptiles possess <it>HoxC3</it>. <it>HoxC1 </it>is only present in caecilians and lobe-finned fishes. Similar to coelacanths, lungfishes also possess <it>HoxA14</it>, which is only found in lobe-finned fishes to date. Our <it>Hox </it>gene variation data favor the lungfish-tetrapod, turtle-archosaur and frog-salamander relationships and imply that the loss of <it>HoxD12 </it>is not directly related to digit reduction.</p> <p>Conclusions</p> <p>Our newly determined <it>Hox </it>inventory data provide a more complete scenario for evolutionary dynamics of <it>Hox </it>genes along the sarcopterygian lineage. Limbless, worm-like caecilians and snakes possess similar <it>Hox </it>gene inventories to animals with less derived body morphology, suggesting changes to their body morphology are likely due to other modifications rather than changes to <it>Hox </it>gene numbers. Furthermore, our results provide basis for future sequencing of the entire <it>Hox </it>clusters of these animals.</p

Coordinated spatial and temporal expression of Hox genes during embryogenesis in the acoel Convolutriloba longifissura

Background: Hox genes are critical for patterning the bilaterian anterior-posterior axis. The evolution of their clustered genomic arrangement and ancestral function has been debated since their discovery. As acoels appear to represent the sister group to the remaining Bilateria (Nephrozoa), investigating Hox gene expression will provide an insight into the ancestral features of the Hox genes in metazoan evolution. Results: We describe the expression of anterior, central and posterior class Hox genes and the ParaHox ortholog Cdx in the acoel Convolutriloba longifissura. Expression of all three Hox genes begins contemporaneously after gastrulation and then resolves into staggered domains along the anterior-posterior axis, suggesting that the spatial coordination of Hox gene expression was present in the bilaterian ancestor. After early surface ectodermal expression, the anterior and central class genes are expressed in small domains of putative neural precursor cells co-expressing ClSoxB1, suggesting an evolutionary early function of Hox genes in patterning parts of the nervous system. In contrast, the expression of the posterior Hox gene is found in all three germ layers in a much broader posterior region of the embryo. Conclusion: Our results suggest that the ancestral set of Hox genes was involved in the anteriorposterior patterning of the nervous system of the last common bilaterian ancestor and were later co-opted for patterning in diverse tissues in the bilaterian radiation. The lack of temporal colinearity of Hox expression in acoels may be due to a loss of genomic clustering in this clade or, alternatively, temporal colinearity may have arisen in conjunction with the expansion of the Hox cluster in the Nephrozoa

Vertebrate Vitellogenin Gene Duplication in Relation to the “3R Hypothesis”: Correlation to the Pelagic Egg and the Oceanic Radiation of Teleosts

The spiny ray-finned teleost fishes (Acanthomorpha) are the most successful group of vertebrates in terms of species diversity. Their meteoric radiation and speciation in the oceans during the late Cretaceous and Eocene epoch is unprecedented in vertebrate history, occurring in one third of the time for similar diversity to appear in the birds and mammals. The success of marine teleosts is even more remarkable considering their long freshwater ancestry, since it implies solving major physiological challenges when freely broadcasting their eggs in the hyper-osmotic conditions of seawater. Most extant marine teleosts spawn highly hydrated pelagic eggs, due to differential proteolysis of vitellogenin (Vtg)-derived yolk proteins. The maturational degradation of Vtg involves depolymerization of mainly the lipovitellin heavy chain (LvH) of one form of Vtg to generate a large pool of free amino acids (FAA 150–200 mM). This organic osmolyte pool drives hydration of the ooctye while still protected within the maternal ovary. In the present contribution, we have used Bayesian analysis to examine the evolution of vertebrate Vtg genes in relation to the “3R hypothesis” of whole genome duplication (WGD) and the functional end points of LvH degradation during oocyte maturation. We find that teleost Vtgs have experienced a post-R3 lineage-specific gene duplication to form paralogous clusters that correlate to the pelagic and benthic character of the eggs. Neo-functionalization allowed one paralogue to be proteolyzed to FAA driving hydration of the maturing oocytes, which pre-adapts them to the marine environment and causes them to float. The timing of these events matches the appearance of the Acanthomorpha in the fossil record. We discuss the significance of these adaptations in relation to ancestral physiological features, and propose that the neo-functionalization of duplicated Vtg genes was a key event in the evolution and success of the teleosts in the oceanic environment

Tissue-specific autoantibodies and autoimmune disorders in vitiligo and alopecia areata: a retrospective study

We retrospectively analyzed our laboratory reports of tissue-specific autoantibodies (TSA) in 38 patients with alopecia areata (AA) and 31 patients with vitiligo. These reports were based on standard indirect immunofluorescence (IF) procedures, employing monkey tissues as substrates. One or more TSA were detected in 39% of serum samples. Thyroid (microsomal and/or thyroglobulin) antibodies had the highest occurrence rate and, as compared with the normal population, were detected at a greater frequency in both vitiligo and AA. Over half (58%) of our patients with vitiligo had one or more detectable TSA, while only 28% of patients with AA had such antibodies. When compared with the normal population, the occurrence rate of TSA was higher in patients with vitiligo. The only remarkable finding in AA was a higher than normal occurrence rate of antithyroid antibodies