Emergence of Xin Demarcates a Key Innovation in Heart Evolution

The mouse Xin repeat-containing proteins (mXinα and mXinβ) localize to the intercalated disc in the heart. mXinα is able to bundle actin filaments and to interact with β-catenin, suggesting a role in linking the actin cytoskeleton to N-cadherin/β-catenin adhesion. mXinα-null mouse hearts display progressively ultrastructural alterations at the intercalated discs, and develop cardiac hypertrophy and cardiomyopathy with conduction defects. The up-regulation of mXinβ in mXinα-deficient mice suggests a partial compensation for the loss of mXinα. To elucidate the evolutionary relationship between these proteins and to identify the origin of Xin, a phylogenetic analysis was done with 40 vertebrate Xins. Our results show that the ancestral Xin originated prior to the emergence of lamprey and subsequently underwent gene duplication early in the vertebrate lineage. A subsequent teleost-specific genome duplication resulted in most teleosts encoding at least three genes. All Xins contain a highly conserved β-catenin-binding domain within the Xin repeat region. Similar to mouse Xins, chicken, frog and zebrafish Xins also co-localized with β-catenin to structures that appear to be the intercalated disc. A putative DNA-binding domain in the N-terminus of all Xins is strongly conserved, whereas the previously characterized Mena/VASP-binding domain is a derived trait found only in Xinαs from placental mammals. In the C-terminus, Xinαs and Xinβs are more divergent relative to each other but each isoform from mammals shows a high degree of within-isoform sequence identity. This suggests different but conserved functions for mammalian Xinα and Xinβ. Interestingly, the origin of Xin ca. 550 million years ago coincides with the genesis of heart chambers with complete endothelial and myocardial layers. We postulate that the emergence of the Xin paralogs and their functional differentiation may have played a key role in the evolutionary development of the heart

Comparative physical maps derived from BAC end sequences of tilapia (Oreochromis niloticus)

Background: The Nile tilapia is the second most important fish in aquaculture. It is an excellent laboratory model, and is closely related to the African lake cichlids famous for their rapid rates of speciation. A suite of genomic resources has been developed for this species, including genetic maps and ESTs. Here we analyze BAC endsequences to develop comparative physical maps, and estimate the number of genome rearrangements, between tilapia and other model fish species. Results: We obtained sequence from one or both ends of 106,259 tilapia BACs. BLAST analysis against the genome assemblies of stickleback, medaka and pufferfish allowed identification of homologies for approximately 25,000 BACs for each species. We calculate that rearrangement breakpoints between tilapia and these species occur about every 3 Mb across the genome. Analysis of 35,000 clones previously assembled into contigs by restriction fingerprints allowed identification of longer-range syntenies. Conclusions: Our data suggest that chromosomal evolution in recent teleosts is dominated by alternate loss of gene duplicates, and by intra-chromosomal rearrangements (~one per million years). These physical maps are a useful resource for comparative positional cloning of traits in cichlid fishes. The paired BAC end sequences from these clones will be an important resource for scaffolding forthcoming shotgun sequence assemblies of the tilapia genome. (Résumé d'auteur

Basal Jawed Vertebrate Phylogenomics Using Transcriptomic Data from Solexa Sequencing

The traditionally accepted relationships among basal jawed vertebrates have been challenged by some molecular phylogenetic analyses based on mitochondrial sequences. Those studies split extant gnathostomes into two monophyletic groups: tetrapods and piscine branch, including Chondrichthyes, Actinopterygii and sarcopterygian fishes. Lungfish and bichir are found in a basal position on the piscine branch. Based on transcriptomes of an armored bichir (Polypterus delhezi) and an African lungfish (Protopterus sp.) we generated, expressed sequences and whole genome sequences available from public databases, we obtained 111 genes to reconstruct the phylogenetic tree of basal jawed vertebrates and estimated their times of divergence. Our phylogenomic study supports the traditional relationship. We found that gnathostomes are divided into Chondrichthyes and the Osteichthyes, both with 100% support values (posterior probabilities and bootstrap values). Chimaeras were found to have a basal position among cartilaginous fishes with a 100% support value. Osteichthyes were divided into Actinopterygii and Sarcopterygii with 100% support value. Lungfish and tetrapods form a monophyletic group with 100% posterior probability. Bichir and two teleost species form a monophyletic group with 100% support value. The previous tree, based on mitochondrial data, was significantly rejected by an approximately unbiased test (AU test, p = 0). The time of divergence between lungfish and tetrapods was estimated to be 391.8 Ma and the divergence of bichir from pufferfish and medaka was estimated to be 330.6 Ma. These estimates closely match the fossil record. In conclusion, our phylogenomic study successfully resolved the relationship of basal jawed vertebrates based on transtriptomes, EST and whole genome sequences

Development and testing of innovative patient resources for the management of coronary heart disease (CHD): a descriptive study

BACKGROUND: Although heart disease is a major cause of morbidity and mortality the majority of patients do not access existing rehabilitation programs and patient resources are not designed to facilitate patient choice and decision-making. The objective of this study was to develop and test a series of risk factor modules and corresponding patient information leaflets for secondary prevention of CHD. METHODS: In phase one, a series of risk factor modules and management options were developed following analysis of literature and interviews with health professionals. In phase two, module information leaflets were developed using published guidelines and interviews of people with CHD. In phase three, the leaflets were tested for quality (DISCERN), readability (Flesch) and suitability (SAM) and were compared to the existing cardiac rehabilitation (CR) information leaflet. Finally, the patients assessed the leaflets for content and relevance. RESULTS: Four key risk factors identified were cholesterol, blood pressure, smoking and physical inactivity. Choice management options were selected for each risk factor and included medical consultation, intensive health professional led program, home program and self direction. Patient information needs were then identified and leaflets were developed. DISCERN quality scores were high for cholesterol (62/80), blood pressure (59/80), smoking (62/80) and physical activity (62/80), all scoring 4/5 for overall rating. The mean Flesch readability score was 75, representing "fairly easy to read", all leaflets scored in the superior category for suitability and were reported to be easy to understand, useful and motivating by persons with CHD risk factors. The developed leaflets scored higher on each assessment than the existing CR leaflets. CONCLUSION: Using a progressive three phase approach, a series of risk factor modules and information leaflets were successfully developed and tested. The leaflets will contribute to shared-decision making and empowerment for persons with CHD

Primitive Duplicate Hox Clusters in the European Eel's Genome

The enigmatic life cycle and elongated body of the European eel (Anguilla anguilla L., 1758) have long motivated scientific enquiry. Recently, eel research has gained in urgency, as the population has dwindled to the point of critical endangerment. We have assembled a draft genome in order to facilitate advances in all provinces of eel biology. Here, we use the genome to investigate the eel's complement of the Hox developmental transcription factors. We show that unlike any other teleost fish, the eel retains fully populated, duplicate Hox clusters, which originated at the teleost-specific genome duplication. Using mRNA-sequencing and in situ hybridizations, we demonstrate that all copies are expressed in early embryos. Theories of vertebrate evolution predict that the retention of functional, duplicate Hox genes can give rise to additional developmental complexity, which is not immediately apparent in the adult. However, the key morphological innovation elsewhere in the eel's life history coincides with the evolutionary origin of its Hox repertoire

A Phylogenetic Perspective on the Evolution of Mediterranean Teleost Fishes

The Mediterranean Sea is a highly diverse, highly studied, and highly impacted biogeographic region, yet no phylogenetic reconstruction of fish diversity in this area has been published to date. Here, we infer the timing and geographic origins of Mediterranean teleost species diversity using nucleotide sequences collected from GenBank. We assembled a DNA supermatrix composed of four mitochondrial genes (12S ribosomal DNA, 16S ribosomal DNA, cytochrome c oxidase subunit I and cytochrome b) and two nuclear genes (rhodopsin and recombination activating gene I), including 62% of Mediterranean teleost species plus 9 outgroups. Maximum likelihood and Bayesian phylogenetic and dating analyses were calibrated using 20 fossil constraints. An additional 124 species were grafted onto the chronogram according to their taxonomic affinity, checking for the effects of taxonomic coverage in subsequent diversification analyses. We then interpreted the time-line of teleost diversification in light of Mediterranean historical biogeography, distinguishing non-endemic natives, endemics and exotic species. Results show that the major Mediterranean orders are of Cretaceous origin, specifically ∼100–80 Mya, and most Perciformes families originated 80–50 Mya. Two important clade origin events were detected. The first at 100–80 Mya, affected native and exotic species, and reflects a global diversification period at a time when the Mediterranean Sea did not yet exist. The second occurred during the last 50 Mya, and is noticeable among endemic and native species, but not among exotic species. This period corresponds to isolation of the Mediterranean from Indo-Pacific waters before the Messinian salinity crisis. The Mediterranean fish fauna illustrates well the assembly of regional faunas through origination and immigration, where dispersal and isolation have shaped the emergence of a biodiversity hotspot

Adaptation of pineal expressed teleost exo-rod opsin to non-image forming photoreception through enhanced Meta II decay

Photoreception by vertebrates enables both image-forming vision and non-image-forming responses such as circadian photoentrainment. Over the recent years, distinct non-rod non-cone photopigments have been found to support circadian photoreception in diverse species. By allowing specialization to this sensory task a selective advantage is implied, but the nature of that specialization remains elusive. We have used the presence of distinct rod opsin genes specialized to either image-forming (retinal rod opsin) or non-image-forming (pineal exo-rod opsin) photoreception in ray-finned fish (Actinopterygii) to gain a unique insight into this problem. A comparison of biochemical features for these paralogous opsins in two model teleosts, Fugu pufferfish (Takifugu rubripes) and zebrafish (Danio rerio), reveals striking differences. While spectral sensitivity is largely unaltered by specialization to the pineal environment, in other aspects exo-rod opsins exhibit a behavior that is quite distinct from the cardinal features of the rod opsin family. While they display a similar thermal stability, they show a greater than tenfold reduction in the lifetime of the signaling active Meta II photoproduct. We show that these features reflect structural changes in retinal association domains of helices 3 and 5 but, interestingly, not at either of the two residues known to define these characteristics in cone opsins. Our findings suggest that the requirements of non-image-forming photoreception have lead exo-rod opsin to adopt a characteristic that seemingly favors efficient bleach recovery but not at the expense of absolute sensitivity

Hox cluster duplication in the basal teleost Hiodon alosoides (Osteoglossomorpha)

Large-scale—even genome-wide—duplications have repeatedly been invoked as an explanation for major radiations. Teleosts, the most species-rich vertebrate clade, underwent a “fish-specific genome duplication” (FSGD) that is shared by most ray-finned fish lineages. We investigate here the Hox complement of the goldeye (Hiodon alosoides), a representative of Osteoglossomorpha, the most basal teleostean clade. An extensive PCR survey reveals that goldeye has at least eight Hox clusters, indicating a duplicated genome compared to basal actinopterygians. The possession of duplicated Hox clusters is uncoupled to species richness. The Hox system of the goldeye is substantially different from that of other teleost lineages, having retained several duplicates of Hox genes for which crown teleosts have lost at least one copy. A detailed analysis of the PCR fragments as well as full length sequences of two HoxA13 paralogs, and HoxA10 and HoxC4 genes places the duplication event close in time to the divergence of Osteoglossomorpha and crown teleosts. The data are consistent with—but do not conclusively prove—that Osteoglossomorpha shares the FSGD

The calcium channel β2 (CACNB2) subunit repertoire in teleosts

© 2008 Ebert et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Does physical activity change predict functional recovery in low back pain? Protocol for a prospective cohort study

Background: Activity advice and prescription are commonly used in the management of low back pain (LBP). Although there is evidence for advising patients with LBP to remain active, facilitating both recovery and return to work, to date no research has assessed whether objective measurements of free living physical activity (PA) can predict outcome, recovery and course of LBP. Methods: An observational longitudinal study will investigate PA levels in a cohort of community-dwelling working age adults with acute and sub-acute LBP. Each participant's PA level, functional status, mood, fear avoidance behaviours, and levels of pain, psychological distress and occupational activity will be measured on three occasions during for 1 week periods at baseline, 3 months, and 1 year. Physical activity levels will be measured by self report, RT3 triaxial accelerometer, and activity recall questionnaires. The primary outcome measure of functional recovery will be the Roland Morris Disability Questionnaire (RMDQ). Free living PA levels and changes in functional status will be quantified in order to look at predictive relationships between levels and changes in free living PA and functional recovery in a LBP population. Discussion: This research will investigate levels and changes in activity levels of an acute LBP cohort and the predictive relationship to LBP recovery. The results will assess whether occupational, psychological and behavioural factors affect the relationship between free living PA and LBP recovery. Results from this research will help to determine the strength of evidence supporting international guidelines that recommend restoration of normal activity in managing LBP. Trial registration. [Clinical Trial Registration Number, ACTRN12609000282280]. © 2009 Hendrick et al; licensee BioMed Central Ltd