25 research outputs found

    Only true pelagics mix : comparative phylogeography of deepwater bathybatine cichlids from Lake Tanganyika

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    In the absence of dispersal barriers, species with great dispersal ability are expected to show little, if at all, phylogeographic structure. The East African Great Lakes and their diverse fish faunas provide opportunities to test this hypothesis in pelagic fishes, which are presumed to be highly mobile and unrestricted in their movement by physical barriers. Here, we address the link between panmixis and pelagic habitat use by comparing the phylogeographic structure among four deepwater cichlid species of the tribe Bathybatini from Lake Tanganyika. We show that the mitochondrial genealogies (based on the most variable part or the control region) of the four species are very shallow (0.8–4% intraspecific divergence across entire distribution ranges) and that all species experienced recent population growth. A lack of phylogeographic structure in the two eupelagic species, Bathybates fasciatus and B. leo, was consistent with expectations and with findings in other pelagic cichlid species. Contrary to expectations, a clear phylogeographic structure was detected in the two benthopelagic species, B. graueri and Hemibates stenosoma. Differences in genetic diversity between eupelagic and benthopelagic species may be due to differences in their dispersal propensity, mediated by their respective predatory niches, rather than precipitated by external barriers to dispersal.Peer reviewe

    The Role of Alternative Splicing and Differential Gene Expression in Cichlid Adaptive Radiation

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    Species diverge eco-morphologically through the continuous action of natural selection on functionally important structures, producing alternative adaptive morphologies. In cichlid fishes, the oral and pharyngeal jaws are such key structures. Adaptive variation in jaw morphology contributes to trophic specialization, which is hypothesized to fuel their rapid speciation in the East African Great Lakes. Much is known about the genes involved in cichlid jaw and craniofacial development. However, it is still unclear what salient sources of variation gave rise to trophic-niche specialization, facilitating adaptive radiation. Here, we explore two sources of transcriptional variation that may underlie species-specific disparities in jaw morphology. Using whole transcriptome RNA-sequencing, we analyze differences in gene expression and alternative splicing, at the end of postlarval development, in fully functional jaws of six species of cichlids from the Lake Tanganyika tribe Tropheini. Our data reveal a surprisingly high degree of alternative splicing events compared with gene expression differences among species and trophic types. This suggests that differential trophic adaptation of the jaw apparatus may have been shaped by transcriptional rewiring of splicing as well as gene expression variation during the rapid radiation of the Tropheini. Specifically, genes undergoing splicing across most species were found to be enriched for pharyngeal jaw gene ontology terms. Overall, jaw transcriptional patterns at postlarval developmental stage were highly dynamic and species-specific. In conclusion, this work indicates that shifts in alternative splicing could have played a more important role in cichlid adaptive radiation, and possibly adaptive radiation in general, than currently recognized.publishe

    A separate lowstand lake at the northern edge of Lake Tanganyika? Evidence from phylogeographic patterns in the cichlid genus Tropheus

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    In Lake Tanganyika, lake level fluctua- tions were shown to have had a major impact on the evolution of littoral species. Many species are subdi- vided into arrays of populations, geographical races and sister species, each colonizing a particular section of the shore. Their often limited dispersal abilities promoted geographic isolation and, on the long run, allopatric speciation. With more than 120 distinct populations, the genus Tropheus represents the most spectacular and best-studied example of this phe- nomenon. The present study aims at the fine-scale reconstruction of the spread of two mitochondrial Tropheus-lineages in the very north of the lake, where two species, T. sp. ‘black’ and T. brichardi, occur. Using mtDNA sequences and AFLP-data, we analyzed samples from 21 localities and found a highly complex conglomerate of introgressed populations formed by the repeated contact of two lineages. Our data suggest repeated cross-lake dispersal of T. sp. ‘black’ haplotypes along the ridge between the West and East Ubwari Fault, supporting an additional persisting lowstand-lake in the Bujumbura subbasin at the very north of the lake and highlighting once more the impact of lake level fluctuations on the genetic structure and evolution of stenotopic rock- dwelling cichlid species.status: publishe

    Flexible Fragment Growing Boosts Potency of Quorum Sensing Inhibitors against Pseudomonas aeruginosa Virulence.

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    Hit-to-lead optimization is a critical phase in drug discovery. Herein, we report on the fragment-based discovery and optimization of 2-amino pyridine derivatives as a novel lead-like structure for the treatment of the dangerous opportunistic pathogen Pseudomonas aeruginosa . We pursue an innovative treatment strategy by interfering with the Pseudomonas Quinolone Signal (PQS) Quorum Sensing (QS) system leading to an abolishment of bacterial pathogenicity. Our compounds act on the PQS receptor (PqsR), a key transcription factor controlling the expression of various pathogenicity determinants. In this target-driven approach, we made use of biophysical screening via surface plasmon resonance (SPR) followed by isothermal titration calorimetry (ITC)-enabled enthalpic efficiency (EE) evaluation. Hit optimization then involved growth vector identification and exploitation. Astonishingly, the latter was successfully achieved by introducing flexible linkers rather than rigid motifs leading to a boost in activity on the target receptor and anti-virulence potency

    Increasing the Yield in Targeted Next-Generation Sequencing by Implicating CNV Analysis, Non-Coding Exons and the Overall Variant Load: The Example of Retinal Dystrophies

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    <div><p>Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are major causes of blindness. They result from mutations in many genes which has long hampered comprehensive genetic analysis. Recently, targeted next-generation sequencing (NGS) has proven useful to overcome this limitation. To uncover “hidden mutations” such as copy number variations (CNVs) and mutations in non-coding regions, we extended the use of NGS data by quantitative readout for the exons of 55 RP and LCA genes in 126 patients, and by including non-coding 5′ exons. We detected several causative CNVs which were key to the diagnosis in hitherto unsolved constellations, e.g. hemizygous point mutations in consanguineous families, and CNVs complemented apparently monoallelic recessive alleles. Mutations of non-coding exon 1 of <i>EYS</i> revealed its contribution to disease. In view of the high carrier frequency for retinal disease gene mutations in the general population, we considered the overall variant load in each patient to assess if a mutation was causative or reflected accidental carriership in patients with mutations in several genes or with single recessive alleles. For example, truncating mutations in <i>RP1</i>, a gene implicated in both recessive and dominant RP, were causative in biallelic constellations, unrelated to disease when heterozygous on a biallelic mutation background of another gene, or even non-pathogenic if close to the C-terminus. Patients with mutations in several loci were common, but without evidence for di- or oligogenic inheritance. Although the number of targeted genes was low compared to previous studies, the mutation detection rate was highest (70%) which likely results from completeness and depth of coverage, and quantitative data analysis. CNV analysis should routinely be applied in targeted NGS, and mutations in non-coding exons give reason to systematically include 5′-UTRs in disease gene or exome panels. Consideration of all variants is indispensable because even truncating mutations may be misleading.</p></div

    Causative mutations and putatively pathogenic variants identified in this study.

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    <p>Causative alleles are being listed as “allele 1” and “allele 2” in resolved cases. Additional alleles are shown if the minor allele frequency is below 3% and if <i>in silico</i> prediction suggests putative pathogenicity. The inheritance pattern was largely delineated from pedigree informations. In patients 22, 23, 77, 100, 116 and 119, the true mode of inheritance had not been evident from the pedigree information and was finally deduced from the genotype. a, this study. References for studies cited in this table can be found in the Supplementary Material (References S1 in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078496#pone.0078496.s001" target="_blank">File S1</a>). n.d., not defined; f, female; m, male; ar, autosomal recessive; ad, autosomal dominant; s, sporadic. Xl, X-linked. Cau, Caucasian; Ger, Germany; Tur, Turkey; KSA, Kingdom of Saudi Arabia; Pol, Poland; Au, Austria; Syr, Syria; Pak, Pakistan; DRC, Democratic Republic of the Congo; Mor, Morocco; UAE, United Arab Emirates; E-Eur, East Europe; SE-Eur, Southeast Europe.</p
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