Indirect development with an intermediate larva exists in all major animal lineages
, which makes larvae central to most scenarios of animal evolution
. Yet how larvae evolved remains disputed. Here ...we show that temporal shifts (that is, heterochronies) in trunk formation underpin the diversification of larvae and bilaterian life cycles. We performed chromosome-scale genome sequencing in the annelid Owenia fusiformis with transcriptomic and epigenomic profiling during the life cycles of this and two other annelids. We found that trunk development is deferred to pre-metamorphic stages in the feeding larva of O. fusiformis but starts after gastrulation in the non-feeding larva with gradual metamorphosis of Capitella teleta and the direct developing embryo of Dimorphilus gyrociliatus. Accordingly, the embryos of O. fusiformis develop first into an enlarged anterior domain that forms larval tissues and the adult head
. Notably, this also occurs in the so-called 'head larvae' of other bilaterians
, with which the O. fusiformis larva shows extensive transcriptomic similarities. Together, our findings suggest that the temporal decoupling of head and trunk formation, as maximally observed in head larvae, facilitated larval evolution in Bilateria. This diverges from prevailing scenarios that propose either co-option
or innovation
of gene regulatory programmes to explain larva and adult origins.
Bacterial symbioses allow annelids to colonise extreme ecological niches, such as hydrothermal vents and whale falls. Yet, the genetic principles sustaining these symbioses remain unclear. Here, we ...show that different genomic adaptations underpin the symbioses of phylogenetically related annelids with distinct nutritional strategies. Genome compaction and extensive gene losses distinguish the heterotrophic symbiosis of the bone-eating worm Osedax frankpressi from the chemoautotrophic symbiosis of deep-sea Vestimentifera. Osedax's endosymbionts complement many of the host's metabolic deficiencies, including the loss of pathways to recycle nitrogen and synthesise some amino acids. Osedax's endosymbionts possess the glyoxylate cycle, which could allow more efficient catabolism of bone-derived nutrients and the production of carbohydrates from fatty acids. Unlike in most Vestimentifera, innate immunity genes are reduced in O. frankpressi, which, however, has an expansion of matrix metalloproteases to digest collagen. Our study supports that distinct nutritional interactions influence host genome evolution differently in highly specialised symbioses.
Abstract Background DNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are ...hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as “mosaic”. Yet, the role and developmental dynamics of 5mC and how these explain interspecies differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla. Results Here, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, alongside a gradual and global, age-dependent demethylation in adult stages. Additionally, reducing 5mC levels with cytidine analogs during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis . Conclusions Our study indicates that global epigenetic erosion during development and aging is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely more important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.
Functional genomics in Spiralia Martín-Zamora, Francisco M; Davies, Billie E; Donnellan, Rory D ...
Briefings in Functional Genomics,
11/2023, Volume:
22, Issue:
6
Journal Article
Open access
Abstract
Our understanding of the mechanisms that modulate gene expression in animals is strongly biased by studying a handful of model species that mainly belong to three groups: Insecta, Nematoda ...and Vertebrata. However, over half of the animal phyla belong to Spiralia, a morphologically and ecologically diverse animal clade with many species of economic and biomedical importance. Therefore, investigating genome regulation in this group is central to uncovering ancestral and derived features in genome functioning in animals, which can also be of significant societal impact. Here, we focus on five aspects of gene expression regulation to review our current knowledge of functional genomics in Spiralia. Although some fields, such as single-cell transcriptomics, are becoming more common, the study of chromatin accessibility, DNA methylation, histone post-translational modifications and genome architecture are still in their infancy. Recent efforts to generate chromosome-scale reference genome assemblies for greater species diversity and optimise state-of-the-art approaches for emerging spiralian research systems will address the existing knowledge gaps in functional genomics in this animal group.
Abstract
Fox genes are a large and conserved family of transcription factors involved in many key biological processes, including embryogenesis and body patterning. Although the role of Fox genes has ...been studied in an array of model systems, comprehensive comparative studies in Spiralia—a large clade of invertebrate animals including molluscs and annelids—are scarce but much needed to better understand the evolutionary history of this gene family. Here, we reconstruct and functionally characterize the Fox gene complement in the annelid Owenia fusiformis, a slow evolving species and member of the sister group to all remaining annelids. The genome of O. fusiformis contains at least a single ortholog for 20 of the 22 Fox gene classes that are ancestral to Bilateria, including an ortholog of the recently discovered foxT class. Temporal and spatial expression dynamics reveal a conserved role of Fox genes in gut formation, mesoderm patterning, and apical organ and cilia formation in Annelida and Spiralia. Moreover, we uncover an ancestral expansion of foxQ2 genes in Spiralia, represented by 11 paralogs in O. fusiformis. Notably, although all foxQ2 copies have apical expression in O. fusiformis, they show variable spatial domains and staggered temporal activation, which suggest cooperation and sub-functionalization among foxQ2 genes for the development of apical fates in this annelid. Altogether, our study informs the evolution and developmental roles of Fox genes in Annelida and Spiralia generally, providing the basis to explore how regulatory changes in Fox gene expression might have contributed to developmental and morphological diversification in Spiralia.
A firm mattress is commonly believed to be beneficial for low-back pain, although evidence supporting this recommendation is lacking. We assessed the effect of different firmnesses of mattresses on ...the clinical course of patients with chronic non-specific low-back pain.
In a randomised, double-blind, controlled, multicentre trial, we assessed 313 adults who had chronic non-specific low-back pain, but no referred pain, who complained of backache while lying in bed and on rising. Mattress firmness is rated on a scale developed by the European Committee for Standardisation. The Hs scale starts at 1·0 (firmest) and stops at 10·0 (softest). We randomly assigned participants firm mattresses (Hs=2·3) or medium- firm mattresses (Hs=5·6). We did clinical assessments at baseline and at 90 days. Primary endpoints were improvements in pain while lying in bed, pain on rising, and disability.
At 90 days, patients with medium-firm mattresses had better outcomes for pain in bed (odds ratio 2·36 95% Cl 1·13–4·93), pain on rising (1·93 0·97–3·86), and disability (2·10 1·24–3·56) than did patients with firm mattresses. Throughout the study period, patients with medium-firm mattresses also had less daytime low-back pain (p=0·059), pain while lying in bed (p=0·064), and pain on rising (p=0·008) than did patients with firm mattresses.
A mattress of medium firmness improves pain and disability among patients with chronic non-specific low- back pain.
Follow-up study.
To estimate the influence of fear avoidance beliefs (FAB) on 1-year low back pain (LBP)-related sick leave.
As opposed to Anglo-Saxon and Northern European subjects, in Spanish LBP ...patients the influence of FAB on disability and quality of life is virtually irrelevant.
Twelve primary care and 9 hospital services from 7 different regions of Spain recruited 165 workers who visited the National Health Service for LBP. None was excluded. On their first visit and 14 days later, patients were given 2 independent Visual Analogue Scales (VAS) for LBP and leg pain, as well as the validated Spanish versions of the Fear Avoidance Beliefs (FABQ), Roland-Morris (RMQ), and SF-12 questionnaires. During the following 12-month period, the number of days on sick leave because of LBP was registered.
Differences in sick leave throughout the study period were associated with baseline differences in chronicity, severity of low back (not referred) pain, disability, FAB, physical and mental quality of life, being on sick leave when entering the study, and duration of previous sick leave. Ordinal logistic regression models showed that each additional point in the total FAB baseline score increases by 2.4% the odds of being on sick leave for up to 60 days during the following year and by 7.7% the odds of being sick listed for 61 days or more. Corresponding figures for FAB-Work scores are 4.2% and 11%. No variable modifies the effect of FAB on sick leave.
Although in Spanish patients the influence of FAB on disability and quality of life is irrelevant, baseline FABQ score does influence LBP-related sick leave during the following year. This seems to be a direct effect of FAB, since there is no confounding by any other variable.
The NDI, COM and NPQ are evaluation instruments for disability due to NP. There was no Spanish version of NDI or COM for which psychometric characteristics were known. The objectives of this study ...were to translate and culturally adapt the Spanish version of the Neck Disability Index Questionnaire (NDI), and the Core Outcome Measure (COM), to validate its use in Spanish speaking patients with non-specific neck pain (NP), and to compare their psychometric characteristics with those of the Spanish version of the Northwick Pain Questionnaire (NPQ).
Translation/re-translation of the English versions of the NDI and the COM was done blindly and independently by a multidisciplinary team. The study was done in 9 primary care Centers and 12 specialty services from 9 regions in Spain, with 221 acute, subacute and chronic patients who visited their physician for NP: 54 in the pilot phase and 167 in the validation phase. Neck pain (VAS), referred pain (VAS), disability (NDI, COM and NPQ), catastrophizing (CSQ) and quality of life (SF-12) were measured on their first visit and 14 days later. Patients' self-assessment was used as the external criterion for pain and disability. In the pilot phase, patients' understanding of each item in the NDI and COM was assessed, and on day 1 test-retest reliability was estimated by giving a second NDI and COM in which the name of the questionnaires and the order of the items had been changed.
Comprehensibility of NDI and COM were good. Minutes needed to fill out the questionnaires median, (P25, P75): NDI. 4 (2.2, 10.0), COM: 2.1 (1.0, 4.9). Reliability: ICC, (95%CI): NDI: 0.88 (0.80, 0.93). COM: 0.85 (0.75,0.91). Sensitivity to change: Effect size for patients having worsened, not changed and improved between days 1 and 15, according to the external criterion for disability: NDI: -0.24, 0.15, 0.66; NPQ: -0.14, 0.06, 0.67; COM: 0.05, 0.19, 0.92.
Results of NDI, NPQ and COM were consistent with the external criterion for disability, whereas only those from NDI were consistent with the one for pain. Correlations with VAS, CSQ and SF-12 were similar for NDI and NPQ (absolute values between 0.36 and 0.50 on day 1, between 0.38 and 0.70 on day 15), and slightly lower for COM (between 0.36 and 0.48 on day 1, and between 0.33 and 0.61 on day 15). Correlation between NDI and NPQ: r = 0.84 on day 1, r = 0.91 on day 15. Correlation between COM and NPQ: r = 0.63 on day 1, r = 0.71 on day 15.
Although most psychometric characteristics of NDI, NPQ and COM are similar, those from the latter one are worse and its use may lead to patients' evolution seeming more positive than it actually is. NDI seems to be the best instrument for measuring NP-related disability, since its results are the most consistent with patient's assessment of their own clinical status and evolution. It takes two more minutes to answer the NDI than to answer the COM, but it can be reliably filled out by the patient without assistance.
Clinical Trials Register NCT00349544.
Purpose To assess the efficacy of neuro-reflexotherapy intervention (NRT) for treating temporomandibular joint dysfunction attributed to myofascial pain. Neuro-reflexotherapy intervention consists of ...the temporary implantation of epidermal devices in trigger points in the back and ear. It has shown efficacy, effectiveness, and cost-effectiveness in treating subacute and chronic common back pain. No study, however, has explored its efficacy in treating myofascial temporomandibular joint pain (MF/TMJP). Patients and Methods This was a randomized, double-blind, placebo-controlled trial. Patients with MF/TMJP for more than 3 months in spite of conservative treatment, and with no evidence of major structural damage in the joint, were recruited at the Maxillofacial Department of the Hospital Clínico Universitario, a teaching hospital in Madrid, Spain. Patients were randomly assigned to an intervention group and to a control group. Patients in the treated group underwent 2 NRTs, immediately after baseline assessment and 45 days later. Sham interventions in the control group consisted of placement of the same number of epidermal devices within a 5-cm radius of the target zones. In both groups, conservative treatment during follow-up was allowed and recorded. Patients underwent clinical evaluations on 4 occasions: 5 minutes before intervention, 5 minutes after intervention, and 45 and 90 days later. The preintervention assessment was performed by the physician at the hospital service who included the patient in the study. The 3 follow-up assessments were performed independently by 1 of 2 physicians who had no connection with the research team, and who were blinded to patients' assignments. The primary outcome variable was level of pain severity during jaw movements at the last assessment (90 days), and the key comparison of interest was change in pain over time (pain levels at baseline and at 90 days). Level of pain was measured using a visual analog scale (VAS). Results Fifty-one patients with MF/TMJP were recruited into the study. Random assignment allocated 27 patients to the intervention group, and 24 to the control group. Differences in pain severity in favor of the intervention group appeared immediately after the intervention, persisted for 45 days, and increased after the second intervention. Differences at last follow-up were highly clinically and statistically significant (4 to 5 points on the VAS, P = .000), allowing for patients in the intervention group to cease drug treatment ( P = .005). There were no differences in the evolution of crepitus or clicking in the joint. There were no clinically relevant side effects associated with the intervention. Conclusions For patients in whom conservative treatment has failed, NRT improves the chronic pain associated with MF/TMJP syndrome.
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