Search

Chromosomal inversions can play an important role in divergence and reproductive isolation by building and maintaining distinct allelic combinations between evolutionary lineages. Alternatively, they can take the form of balanced polymorphisms that segregate within populations until one arrangement becomes fixed. Many questions remain about how inversion polymorphisms arise, how they are maintained over the long term, and ultimately, whether and how they contribute to speciation. The long-snouted seahorse (Hippocampus guttulatus) is genetically subdivided into geographic lineages and marine-lagoon ecotypes, with shared structural variation underlying lineage and ecotype divergence. Here, we aim to characterize structural variants and to reconstruct their history and suspected role in ecotype formation. We generated a near chromosome-level genome assembly and described genome-wide patterns of diversity and divergence through the analysis of 112 whole-genome sequences from Atlantic, Mediterranean, and Black Sea populations. By also analysing linked-read sequencing data, we found evidence for two chromosomal inversions that were several megabases in length and showed contrasting allele frequency patterns between lineages and ecotypes across the species range. We reveal that these inversions represent ancient intraspecific polymorphisms, one likely being maintained by divergent selection and the other by pseudo-overdominance. A possible selective coupling between the two inversions was further supported by the absence of specific haplotype combinations and a putative functional interaction between the two inversions in reproduction. Lastly, we detected gene flux eroding divergence between inverted alleles at varying levels for the two inversions, with a likely impact on their dynamics and contribution to divergence and speciation., (© 2024 John Wiley & Sons Ltd.)

Cystoseira sensu lato (Class Phaeophyceae, Order Fucales, Family Sargassaceae) forests play a central role in marine Mediterranean ecosystems. Over the last decades, Cystoseira s.l. suffered from a severe loss as a result of multiple anthropogenic stressors. In particular, Gongolaria barbata has faced multiple human-induced threats, and, despite its ecological importance in structuring rocky communities and hosting a large number of species, the natural recovery of G. barbata depleted populations is uncertain. Here, we used nine microsatellite loci specifically developed for G. barbata to assess the genetic diversity of this species and its genetic connectivity among fifteen sites located in the Ionian, the Adriatic and the Black Seas. In line with strong and significant heterozygosity deficiencies across loci, likely explained by Wahlund effect, high genetic structure was observed among the three seas (ENA corrected F ST  = 0.355, IC = [0.283, 0.440]), with an estimated dispersal distance per generation smaller than 600 m, both in the Adriatic and Black Sea. This strong genetic structure likely results from restricted gene flow driven by geographic distances and limited dispersal abilities, along with genetic drift within isolated populations. The presence of genetically disconnected populations at small spatial scales (< 10 km) has important implications for the identification of relevant conservation and management measures for G. barbata: each population should be considered as separated evolutionary units with dedicated conservation efforts., (© 2021. The Author(s).)

Diverging semi-isolated lineages either meet in narrow clinal hybrid zones, or have a mosaic distribution associated with environmental variation. Intrinsic reproductive isolation is often emphasized in the former and local adaptation in the latter, although both reduce gene flow between groups. Rarely are these two patterns of spatial distribution reported in the same study system. Here, we report that the long-snouted seahorse Hippocampus guttulatus is subdivided into discrete panmictic entities by both types of hybrid zones. Along the European Atlantic coasts, a northern and a southern lineage meet in the southwest of France where they coexist in sympatry-i.e., in the same geographical zone-with little hybridization. In the Mediterranean Sea, two lineages have a mosaic distribution, associated with lagoon-like and marine habitats. A fifth lineage was identified in the Black Sea. Genetic homogeneity over large spatial scales contrasts with isolation maintained in sympatry or close parapatry at a fine scale. A high variation in locus-specific introgression rates provides additional evidence that partial reproductive isolation must be maintaining the divergence. We find that fixed differences between lagoon and marine populations in the Mediterranean Sea belong to the most differentiated SNPs between the two Atlantic lineages, against the genome-wide pattern of structure that mostly follow geography. These parallel outlier SNPs cluster on a single chromosome-wide island of differentiation. Since Atlantic lineages do not map to lagoon-sea habitat variation, genetic parallelism at the genomic island suggests a shared genetic barrier contributes to reproductive isolation in contrasting contexts-i.e., spatial versus ecological. We discuss how a genomic hotspot of parallel differentiation could have evolved and become associated both with space and with a patchy environment in a single study system., (© 2019 The Author(s). Evolution © 2019 The Society for the Study of Evolution.)

In many marine invertebrates, long-distance dispersal is achieved during an extended pelagic larval phase. Although such dispersal should result in high gene flow over broad spatial scales, fine-scale genetic structure has often been reported, a pattern attributed to interfamilial variance in reproductive success and limited homogenization during dispersal. To examine this hypothesis, the genetic diversity of dispersing larvae must be compared with the postdispersal stages, that is benthic recruits and adults. Such data remain, however, scarce due to the difficulty to sample and analyse larvae of minute size. Here, we carried out such an investigation using the marine gastropod Crepidula fornicata. Field sampling of three to four larval pools was conducted over the reproductive season and repeated over 3 years. The genetic composition of larval pools, obtained with 16 microsatellite loci, was compared with that of recruits and adults sampled from the same site and years. In contrast to samples of juveniles and adults, large genetic temporal variations between larval pools produced at different times of the same reproductive season were observed. In addition, full- and half-sibs were detected in early larvae and postdispersal juveniles, pointing to correlated dispersal paths between several pairs of individuals. Inbred larvae were also identified. Such collective larval dispersal was unexpected given the long larval duration of the study species. Our results suggest that each larval pool is produced by a small effective number of reproducers but that, over a reproductive season, the whole larval pool is produced by large numbers of reproducers across space and time., (© 2017 John Wiley & Sons Ltd.)

RIPK3 kinase-mediated phosphorylation of MLKL pseudokinase is the execution event of necroptosis. Two independent reports-in Immunity (Yoon et al., 2017) and Cell (Gong et al., 2017)-reveal that MLKL affects homeostatic membrane trafficking and necroptosis-enhanced bubble formation involving interaction with the ESCRT machinery., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Genetic chimerism is rarely considered in the analysis of population genetics data, because assumed to be an exceptionally rare, mostly benign, developmental accident. An unappreciated source of chimerism is transmissible cancer, when malignant cells have become independent parasites and can infect other individuals. Parasitic cancers were thought to be rare exceptions, only reported in dogs (Murgia et al., Cell , 2006, 126 , 477; Rebbeck et al., Evolution , 2009, 63 , 2340), Tasmanian devils (Pearse and Swift, Nature , 2006, 439 , 549; Pye et al., Proceedings of the National Academy of Sciences , 2016, 113 , 374), and soft-shell clams (Metzger et al., Cell , 2015, 161 , 255). However, the recent simultaneous report of four new contagious leukemias in marine mollusks (Metzger et al., Nature , 2016, 534 , 705) might change the rules. By doubling up the number of naturally occurring transmissible cancers, this discovery suggests they may essentially be missed because not sufficiently searched for, especially outside mammals. We encourage population geneticists to keep in mind infectious cancer when interpreting weird genotypes in their molecular data. It would then contribute in the investigation of how widespread contagious cancer could really be in the wild. We provide an example with our own data in Mytilus mussels, a commercially important shellfish. We identified genetic chimerism in a few mussels that suggests the possible occurrence at low prevalence in European M. edulis populations of a M. trossulus contagious cancer related to the one described by Metzger et al. ( Nature , 2016, 534 , 705) in populations of British Columbia.

Chaotic genetic patchiness (CGP) refers to surprising patterns of spatial and temporal genetic structure observed in some marine species at a scale where genetic variation should be efficiently homogenized by gene flow via larval dispersal. Here we review and discuss 4 mechanisms that could generate such unexpected patterns: selection, sweepstakes reproductive success, collective dispersal, and temporal shifts in local population dynamics. First, we review examples where genetic differentiation at specific loci was driven by diversifying selection, which was historically the first process invoked to explain CGP. Second, we turn to neutral demographic processes that may drive genome-wide effects, and whose effects on CGP may be enhanced when they act together. We discuss how sweepstakes reproductive success accelerates genetic drift and can thus generate genetic structure, provided that gene flow is not too strong. Collective dispersal is another mechanism whereby genetic structure can be maintained regardless of dispersal intensity, because it may prevent larval cohorts from becoming entirely mixed. Theoretical analyses of both the sweepstakes and the collective dispersal ideas are presented. Finally, we discuss an idea that has received less attention than the other ones just mentioned, namely temporal shifts in local population dynamics.

Over the last decade, our picture of cell death signals involved in experimental disease models totally shifted. Indeed, in addition to apoptosis, multiple forms of regulated necrosis have been associated with an increasing number of pathologies such as ischemia-reperfusion injury in brain, heart and kidney, inflammatory diseases, sepsis, retinal disorders, neurodegenerative diseases and infectious disorders. Especially necroptosis is currently attracting the attention of the scientific community. However, the in vivo identification of ongoing necroptosis in experimental disease conditions remains troublesome, mainly due to the lack of specific biomarkers. Initially, Receptor-Interacting Protein Kinase 1 (RIPK1) and RIPK3 kinase activity were uniquely associated with induction of necroptosis, however recent evidence suggests pleiotropic functions in cell death, inflammation and survival, obscuring a clear picture. In this review, we will present the last methodological advances for in vivo necroptosis identification and discuss past and recent data to provide an update of the so-called "necroptosis-associated pathologies"., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In sex-changing animals with internal fertilization, gregarious behavior may increase mating opportunities and the frequency of multiple paternity, thus increasing maternal reproductive success. Crepidula convexa is a direct-developing protandrous gastropod characterized by only modest gregarious behavior compared with previously studied members of the genus: females are frequently found isolated. Using 6 microsatellite markers, we analyzed paternity profiles in 10 broods (25 embryos per mother). The number of assigned fathers varied among families from 1 to 4 fathers per brood. Interestingly, polyandry was not detected in solitary females but only in females grouped with conspecific individuals. Overall, we found an average of 1.8 fathers per brood, but this increased to 2.6 fathers per brood when considering only the nonisolated females. Among 18 unambiguously identified fathers, only 5 were collected in our samples, suggesting substantial male mobility. Comparison with previous paternity analyses in Crepidula fornicata and Crepidula coquimbensis revealed that polyandry appears as a common trait of these sex-changing gastropods despite their different grouping behaviors and life histories. As expected, the level of polyandry was nevertheless lower in the modestly gregarious C. convexa.

Cell death contributes to the maintenance of homeostasis, but mounting evidence has confirmed the involvement of programmed cell death in some diseases. The concept of programmed cell death, which was coined several decades ago to refer to apoptosis, now also encompasses necroptosis, a newly characterized cell death program. Research on programmed cell death has become essential for the development of some new therapies. To study cell death signaling and its molecular mechanisms, new biochemical and fluorogenic approaches have been devised. Here, we first provide an overview of programmed cell death modes and the importance of dynamic cell death studies. Next, we focus on both apoptotic and necroptotic signaling and their mechanisms by providing a systematic review of all the methods and approaches that have been used. We emphasize the contribution of advanced approaches based on fluorescent probes, reporters, and Förster resonance energy transfer (FRET)-based biosensors for studying programmed cell death. Because apoptosis and necroptosis signaling pathways share some effectors molecules, we discuss how these new tools could be used to discriminate between apoptosis and necroptosis. We also describe how we developed specific FRET-based biosensors for detecting necroptosis. Finally, we touch on how dynamic measurement of biomolecules in living models will play a role in personalized prognosis and therapy., (Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Among biosensors, genetically-encoded FRET-based biosensors are widely used to localize and measure enzymatic activities. Kinases activities are of particular interest as their spatiotemporal regulation has become crucial for the deep understanding of cell fate decisions. This is especially the case for ERK, whose activity is a key node in signal transduction pathways and can direct the cell into various processes. There is a constant need for better tools to analyze kinases in vivo, and to detect even the slightest variations of their activities. Here we report the optimization of the previous ERK activity reporters, EKAR and EKAREV. Those tools are constituted by two fluorophores adapted for FRET experiments, which are flanking a specific substrate of ERK, and a domain able to recognize and bind this substrate when phosphorylated. The latter phosphorylation allows a conformational change of the biosensor and thus a FRET signal. We improved those biosensors with modifications of: (i) fluorophores and (ii) linkers between substrate and binding domain, resulting in new versions that exhibit broader dynamic ranges upon EGF stimulation when FRET experiments are carried out by fluorescence lifetime and ratiometric measurements. Herein, we characterize those new biosensors and discuss their observed differences that depend on their fluorescence properties.

Selection processes are believed to be an important evolutionary driver behind the successful establishment of nonindigenous species, for instance through adaptation for invasiveness (e.g. dispersal mechanisms and reproductive allocation). However, evidence supporting this assumption is still scarce. Genome scans have often identified loci with atypical patterns of genetic differentiation (i.e. outliers) indicative of selection processes. Using microsatellite- and AFLP-based genome scans, we looked for evidence of selection following the introduction of the mollusc Crepidula fornicata. Native to the northwestern Atlantic, this gastropod has become an emblematic invader since its introduction during the 19th and 20th centuries in the northeastern Atlantic and northeastern Pacific. We examined 683 individuals from seven native and 15 introduced populations spanning the latitudinal introduction and native ranges of the species. Our results confirmed the previously documented high genetic diversity in native and introduced populations with little genetic structure between the two ranges, a pattern typical of marine invaders. Analysing 344 loci, no outliers were detected between the introduced and native populations or in the introduced range. The genomic sampling may have been insufficient to reveal selection especially if it acts on traits determined by a few genes. Eight outliers were, however, identified within the native range, underlining a genetic singularity congruent with a well-known biogeographical break along the Florida. Our results call into question the relevance of AFLP genome scans in detecting adaptation on the timescale of biological invasions: genome scans often reveal long-term adaptation involving numerous genes throughout the genome but seem less effective in detecting recent adaptation from pre-existing variation on polygenic traits. This study advocates other methods to detect selection effects during biological invasions-for example on phenotypic traits, although genome scans may remain useful for elucidating introduction histories., (© 2013 Blackwell Publishing Ltd.)

In silico mining of an expressed sequence tags (ESTs) library was found to be efficient at isolating simple sequence repeats (SSRs) loci in the non-indigenous marine mollusc Crepidula fornicata. Twelve SSR loci were developed for routine genotyping. Cross-species amplification to 8 other Crepidula species showed that the 12 loci are highly specific for C. fornicata. Mendelian inheritance was shown for 11 of them (1 being monomorphic in the analyzed offspring array). The genetic diversity for 88 adults was found to be variable across the 12 loci (2-40 alleles, expected heterozygosity between 0.023 and 0.898) with a high overall exclusion probability of 0.99. The degree of genetic polymorphism found here is similar to that shown for 7 anonymous SSRs previously developed and here used on the same samples. This set of 12 specific loci is relevant to perform reliable population and relatedness analyses in Crepidula fornicata., (Copyright © 2011 Elsevier B.V. All rights reserved.)

In combination with two photon excitation, FLIM is currently one of the best techniques to quantitatively study the subcellular localization of protein-protein interactions in living cells. An appropriate analysis procedure is crucial to obtain reliable results. TCSPC is an accurate method to measure FLIM. It is however an indirect process that requires photon decay curve fitting, using an exponential decay equation. Although choosing the number of exponential terms is essential, it is labor-intensive and time consuming. Therefore, a mono-model is usually applied to a whole image. Here we propose an algorithm, named Lichi, allowing pixel by pixel analysis based on the Deltachi(2) value. Lichi was validated using simulated photon decay curves with known lifetimes and proportions. It showed a high robustness for decay curves with more than 10(3) photons. When applied to lifetime images acquired from living cells, it resulted in a more realistic representation of the interaction maps. We developed an easy-to-use procedure for multi-model FLIM analysis, which enables optimized FRET quantification for all interaction texture studies, and is especially suitable to avoid the classical misinterpretation of heterogeneous samples., ((c) 2008 International Society for Advancement of Cytometry)

Between October 2001 and April 2002, five cases of acute flaccid paralysis (AFP) associated with type 2 vaccine-derived polioviruses (VDPVs) were reported in the southern province of the Republic of Madagascar. To determine viral factors that favor the emergence of these pathogenic VDPVs, we analyzed in detail their genomic and phenotypic characteristics and compared them with co-circulating enteroviruses. These VDPVs appeared to belong to two independent recombinant lineages with sequences from the type 2 strain of the oral poliovaccine (OPV) in the 5'-half of the genome and sequences derived from unidentified species C enteroviruses (HEV-C) in the 3'-half. VDPV strains showed characteristics similar to those of wild neurovirulent viruses including neurovirulence in poliovirus-receptor transgenic mice. We looked for other VDPVs and for circulating enteroviruses in 316 stools collected from healthy children living in the small area where most of the AFP cases occurred. We found vaccine PVs, two VDPVs similar to those found in AFP cases, some echoviruses, and above all, many serotypes of coxsackie A viruses belonging to HEV-C, with substantial genetic diversity. Several coxsackie viruses A17 and A13 carried nucleotide sequences closely related to the 2C and the 3D(pol) coding regions of the VDPVs, respectively. There was also evidence of multiple genetic recombination events among the HEV-C resulting in numerous recombinant genotypes. This indicates that co-circulation of HEV-C and OPV strains is associated with evolution by recombination, resulting in unexpectedly extensive viral diversity in small human populations in some tropical regions. This probably contributed to the emergence of recombinant VDPVs. These findings give further insight into viral ecosystems and the evolutionary processes that shape viral biodiversity.

Both cell-specific and ubiquitous transcription factors in fibroblasts have been identified as critical for expression of the Col1a1 gene, which encodes the alpha1 chain of type I collagen. Here, we report that Yin Yang 1 (YY1) binds to the Col1a1 promoter immediately upstream of the TATA box, and we examine the functional implications of YY1 binding for regulation of Col1a1 gene expression in BALBc/3T3 fibroblasts. The Col1a1 promoter region spanning base pairs (bp) -56 to -9 bound purified recombinant YY1 and the corresponding binding activity in nuclear extracts was supershifted using a YY1-specific antibody. Mutation of the TATA box to TgTA enhanced YY1 complex formation. Mutation analysis revealed two YY1 core binding sites at -40/-37 bp (YY1A) and, on the reverse strand, at -32/-29 bp (YY1B) immediately adjacent to the TATA box. In transfections using Col1a1-luciferase constructs, mutation of YY1A decreased activity completely (wild-type p350 (p350wt), -222/+113 bp) or partially (p130wt, -84 bp/+13 bp), whereas mutation of YY1B blocked the expression of both promoter constructs. Cotransfection with pCMV-YY1 increased p350wt and p130wt activities by as much as 10-fold, whereas antisense YY1 decreased constitutive expression and blocked the increased activity due to pCMV-YY1 overexpression. The mTgTA constructs were devoid of activity, arguing for a requirement for cognate binding of the TATA box-binding protein (TBP). Electrophoretic mobility shift assays performed under conditions permitting TBP binding showed that recombinant TBP/TFIID and YY1 could bind to the -56/-9 bp fragment and that YY1B was the preferred site for YY1 binding. Our results indicate that YY1 binds to the Col1a1 proximal promoter and functions as a positive regulator of constitutive activity in fibroblasts. Although YY1 is not sufficient for transcriptional initiation, it is a required component of the transcription machinery in this promoter.

Background: Tissues undergoing a chronic inflammatory process, such as the synovium in rheumatoid arthritis, are characterized by the infiltration of lymphocytes of different subsets and activation of monocyte/macrophages. Interleukin-1 (IL-1), a monocyte/ macrophage product that stimulates synovial fibroblasts to produce matrix metalloproteinases (MMPs), prostaglandins, and other cytokines, also has profound effects on the synthesis of extracellular matrix components such as type I collagen. In previous studies, we have shown that synovial fibroblasts and chondrocytes isolated from human joint tissues are particularly sensitive to prostaglandins, which modulate the effects of IL-1 on collagen gene expression in an autocrine manner., Materials and Methods: BALBc/3T3 fibroblasts were treated with IL-1 and prostaglandins in the absence and presence of indomethacin to inhibit endogenous prostaglandin biosynthesis. Collagen synthesis was analyzed by SDS-PAGE as [3H]proline-labeled, secreted proteins, and prostaglandin production and cyclic adenosine 3',5'-cyclic monophosphate (camp) content were assayed. The expression of type I collagen gene (Col1a1) promoter-reporter gene constructs was examined in transient transfection experiments, and the binding of nuclear factors to the Col1a1 promoter region spanning -222 bp/+ 116 bp was analyzed by DNase I footprinting and electrophoretic mobility shift (EMSA) assays., Results: IL-1 increased the synthesis of type I and type III collagens in BALBc/3T3 fibroblasts; greater increases were observed when IL-1-stimulated synthesis of PGE2 was blocked by indomethacin. Transient transfection experiments demonstrated dose-dependent inhibition of the-222 bp Col1a1 promoter by exogenously added prostaglandins with the order of potency of PGF2alpha > PGE2 > PGE1 DNase I footprinting showed increased protection, which extended from the region immediately upstream of the TATA box, owing to the binding of nuclear factors from PGE2- or PGE1-treated BALBc/3T3 cells. EMSA analysis showed zinc-dependent differences in the binding of nuclear factors from untreated and prostaglandin-treated cells to the -84 bp/-29 bp region of the Col1a1 promoter., Conclusions: These results show that the inhibition of Col1a1 expression by IL-1 in fibroblasts is mediated by prostaglandins at the transcriptional level and suggest that PGE-responsive factors may interact directly or indirectly with basal regulatory elements in the proximal promoter region of the Col1a1 gene.