Biology subjects

Lang, M.

Publications and source records attributed to Lang, M..

46 records · Page 3Linked to original sources

bioRxiv2020

Widespread introgression across a phylogeny of 155 Drosophila genomes

Genome-scale sequence data have invigorated the study of hybridization and introgression, particularly in animals. However, outside of a few notable cases, we lack systematic tests for introgression at a larger phylogenetic scale across entire clades. Here we leverage 155 genome assemblies, from 149 species, to generate a fossil-calibrated phylogeny and conduct multilocus tests for introgression across nine monophyletic radiations within the genus Drosophila. Using complementary phylogenomic approaches, we identify widespread introgression across the evolutionary history of Drosophila. Mapping gene-tree discordance onto the phylogeny revealed that both ancient and recent introgression has occurred across most of the nine clades that we examined. Our results provide the first evidence of introgression occurring across the evolutionary history of Drosophila and highlight the need to continue to study the evolutionary consequences of hybridization and introgression in this genus and across the Tree of Life.

evolutionary biology↗

bioRxiv2020

Sleeping ribosomes: bacterial signaling triggers RaiA mediated persistence to aminoglycosides.

Indole is a small molecule derived from tryptophan degradation and proposed to be involved in bacterial signaling. We find that indole secretion is induced by sublethal tobramycin concentrations and increases persistence to aminoglycosides in V. cholerae. Indole transcriptomics showed strongly increased expression of raiA, a ribosome associated factor. Deletion of raiA abolishes the appearance of indole dependent persisters to aminoglycosides, while its overexpression leads to 100-fold increase of persisters, and a reduction in lag phase, evocative of increased active 70S ribosome content, which was confirmed by sucrose gradient analysis. We propose that, under stress conditions, inactive 70S ribosomes are associated with RaiA to be stored and rapidly reactivated when growth conditions become favorable again, in a mechanism different than ribosome hibernation. Our results point to an active process of persistent cell formation, through ribosome protection during translational stress and relief upon antibiotic removal. Translation is a universal process, and these results could help elucidate a mechanism of persistence formation in a controlled, thus inducible way.

microbiology↗

bioRxiv2020

Salicylate, Bile Acids and Extreme Acid Cause Fitness Tradeoffs for Multidrug Pumps in Escherichia coli K-12

The aspirin derivative salicylate selects against bacterial multidrug efflux pumps of Escherichia coli K-12 such as MdtEF-TolC and EmrAB-TolC, and acid stress regulators such as GadE. Salicylate uptake is driven by the transmembrane pH gradient ({Delta}pH) and the proton motive force (PMF) which drives many efflux pumps. We used flow cytometry to measure the fitness tradeoffs of salicylate, bile acids, and extreme low pH for E. coli cultured with pump deletants. The AcrAB-TolC efflux pump conferred a fitness advantage in the presence of bile acids, an efflux substrate. Without bile acids, AcrA incurred a small fitness cost. The fitness advantage with bile acids was eliminated by the PMF uncoupler CCCP. The Gad acid fitness island encodes components of MdtEF-TolC (an acid-adapted efflux pump) as well as acid regulator GadE. The fitness advantage of E. coli cocultured with a Gad deletant ({Delta}slp-gadX) was lost in the presence of salicylate. Salicylate caused an even larger fitness cost for GadE. MdtE incurred negative or neutral fitness under all media conditions, as did EmrA. But when the competition cycle included two hours at pH 2, MdtE conferred a fitness advantage. The MdtE advantage required the presence of bile acids. Thus, the MdtEF-TolC pump is useful to E. coli for transient extreme acid exposure comparable to passage through the acidic stomach. Salicylate selects against some multidrug efflux pumps, whereas bile acids selects for them; and these fitness tradeoffs are amplified by extreme acid. IMPORTANCEControl of drug resistance in gut microbial communities is a compelling problem for human health. Growth of gut bacteria is limited by host-produced acids such as bile acids, and may be modulated by plant-derived acids such as salicylic acid. Membrane-soluble organic acids can control bacterial growth by disrupting membranes, decreasing cell pH, and depleting PMF. Our flow cytometry assay measures the fitness effects of exposure to membrane-soluble organic acids, with growth cycles that may include a period of extreme acid. We find that extreme-acid exposure leads to a fitness advantage for a multidrug pump, MdtEF-TolC, which otherwise incurs a large fitness cost. Thus, organic acids and stomach acid may play important roles in controlling multidrug resistance in the gut microbiome. Therapeutic acids might be developed to limit the prevalence of multidrug resistance pumps in environmental and host-associated communities.

microbiology↗

bioRxiv2020

Excitatory-Inhibitory Balance within EEG Microstates and Resting-state fMRI Networks: Assessed via Simultaneous PET-MR-EEG Imaging

The symbiosis of neuronal activities and glucose energy metabolism is reflected in the generation of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) signals. However, their association with the balance between neuronal excitation and inhibition (E/I-B), which is closely related to the activities of glutamate and GABA ({gamma} -aminobutyric acid) and the receptor availability (RA) of GABAA and mGluR5, remains unexplored. This study investigates these associations during the resting state (RS) condition using simultaneously recorded PET/MR/EEG (trimodal) data. Glucose metabolism and neuroreceptor binding availability (non-displaceable binding potential (BPND)) of GABAA and mGluR5 were found to be significantly higher and closely linked within core resting-state networks (RSNs). The neuronal generators of EEG microstates and the fMRI measures were most tightly associated with the BPND of GABAA relative to mGluR5 BPND and the glucose metabolism, emphasising a predominance of inhibitory processes within in the core RSNs at rest.

neuroscience↗

bioRxiv2020

Population dynamics of decision making in temperate bacteriophages

Due to their ability to choose between lysis and lysogeny, temperate bacteriophages represent a classic model system to study the molecular basis of decision making. The coinfection of individual bacteria by multiple, genetically identical phages is known to alter the infection outcome and favor lysogeny over lytic development. However, it is not clear what role the ability of individual phages to sense and respond to coinfections plays in the phage-host infection dynamics at the population level. To address this question, we developed a full-stochastic model to capture the interaction dynamics between billions of bacteria and phages with single-cell and -phage resolution. While, at the level of individual bacteria, the probability of coinfections depends mainly on the phage concentration at the time of infection, the average number of coinfections at the population level is primarily determined by the relative growth rate of phage. Because the maximum attainable phage growth rate is constrained by basic life history parameters, the average number of coinfections has an upper bound of around two. However, for a broad range of conditions, the average number of coinfections stays well below this value. Consequently, we find that coinfections provide only very limited information to individual phages about the state of the infection at the population level. Nevertheless, this information can still provide a strong competitive advantage for phages that base fate decisions on the number of coinfections.

evolutionary biology↗

bioRxiv2020

Genome-wide Identification and Analysis of Enhancer Regulated microRNAs Across 31 Human Tissues

Enhancers are cis-regulatory DNA elements that positively regulate the transcription of target genes in a tissue-specific manner and dysregulation in various diseases such as cancer. Recent studies showed that enhancers can regulate miRNAs and participate in the biological synthesis of miRNAs. However, the network of enhancer-regulated miRNAs across multiple cancers is still unclear. Here, a total of 2,418 proximal enhancer-miRNA interactions and 1,280 distal enhancer-miRNA interactions were identified through the integration of genomic distance, co-expression, and 3D genome data in 31 cancers. The results showed that both proximal and distal interactions exhibited significant tissue-specific feature and there was a noteworthy positive correlation between the expression of miRNA and the number of regulated enhancers in most tissues. Furthermore, it was found that there was a high correlation between the formation of enhancer-miRNA pairs and the expression of eRNAs whether in distal or proximal regulation. The characteristics analysis showed that miRes (enhancers that regulated miRNAs) and non-miRes presented significant differences in sequence conservation, GC content and histone modification signatures. Notably, GC content, H3K4me1, H3K36me3 were present differently between distal regulation and proximal regulation, suggesting they might participate in chromosome looping of enhancer-miRNA interactions. Finally, we introduced a case study, enhancer: chr1:1186391-1186507[~]miR-200a was highly relevant to the survival of thyroid cancer patients and a cis-eQTL SNP on enhancer affected the expression TNFRSF18 gene as a tumor suppressor.

bioinformatics↗

bioRxiv2019

A primary sexual trait involved in courtship in insects: Male genital lobe morphology affects the chance to copulate in Drosophila pachea

IntroductionMale genitalia are thought to ensure transfer of sperm through direct physical contact with female during copulation. However, little attention has been given to their pre-copulatory role with respect to sexual selection and sexual conflict. Males of the fruitfly Drosophila pachea have a pair of asymmetric external genital lobes, which are primary sexual structures and stabilize the copulatory complex of female and male genitalia. We wondered if genital lobes in D. pachea may have a role before or at the onset of copulation, before genitalia contacts are made. ResultsWe tested this hypothesis with a D. pachea stock where males have variable lobe lengths. In 92 mate competition trials with a single female and two males, females preferentially engaged into a first copulation with males that had a longer left lobe and that displayed increased courtship vigor. In 53 additional trials with both males having partially amputated left lobes of different lengths, we observed a weaker and non-significant effect of left lobe length on copulation success. Courtship durations significantly increased with female age and when two males courted the female simultaneously, compared to trials with only one courting male. In addition, lobe length did not affect sperm transfer once copulation was established. ConclusionLeft lobe length affects the chance of a male to engage into copulation. The morphology of this primary sexual trait may affect reproductive success by mediating courtship signals or by facilitating the establishment of genital contacts at the onset of copulation.

evolutionary biology↗

bioRxiv2019

Repeated evolution of asymmetric genitalia and right-sided mating behavior in the Drosophila nannoptera species group

BackgroundMale genitals have repeatedly evolved left-right asymmetries, and the causes of such evolution remain unclear. The Drosophila nannoptera group contains four species, among which three exhibit left-right asymmetries of distinct genital organs. In the most studied species, Drosophila pachea, males display asymmetric genital lobes and they mate right-sided on top of the female. Copulation position of the other species is unknown. ResultsTo assess whether the evolution of genital asymmetry could be linked to the evolution of one-sided mating, we examined phallus morphology and copulation position in D. pachea and closely related species. The phallus was found to be symmetric in all investigated species except D. pachea, which display an asymmetric phallus with a right-sided gonopore, and D. acanthoptera, which harbor an asymmetrically bent phallus. In all examined species, males were found to position themselves symmetrically on top of the female, except in D. pachea and D. nannoptera, where males mated right-sided, in distinctive, species-specific positions. In addition, the copulation duration was found to be increased in nannoptera group species compared to closely related outgroup species. ConclusionOur study shows that gains, and possibly losses, of asymmetry in genital morphology and mating position have evolved repeatedly in the nannoptera group. Current data does not allow us to conclude whether genital asymmetry has evolved in response to changes in mating position, or vice versa.

evolutionary biology↗

bioRxiv2018

Correlated Evolution of two Sensory Organs via a Single Cis-Regulatory Nucleotide Change

Diverse traits often covary between species. The possibility that a single mutation could contribute to the evolution of several characters between species is rarely investigated as relatively few cases are dissected at the nucleotide level. Drosophila santomea has evolved additional sex comb sensory teeth on its legs and has lost two sensory bristles on its genitalia. We found that a single nucleotide substitution in an enhancer of the scute gene contributes to both changes. The mutation alters a binding site for the Hox protein Abdominal-B in the developing genitalia, leading to bristle loss, and for another factor in the developing leg, leading to bristle gain. Our study shows that morphological evolution between species can occur through a single nucleotide change affecting several sexually dimorphic traits.\n\nOne Sentence SummaryWe identify one nucleotide substitution in a gene regulatory region contributing to evolutionary change of two distinct organs.

evolutionary biology↗

bioRxiv2018

Evolution of sexually-transferred steroids in Anopheles mosquitoes

Human malaria, which remains a major public health problem, is transmitted by a subset of Anopheles mosquitoes belonging to only three out of eight subgenera: Anopheles, Cellia and Nyssorhynchus. Unlike almost every other insect species, it was shown that males of some Anopheles species produce and transfer steroid hormones to females during copulation and that this transfer mediates reproductive changes. Steroids are consequently seen as a potential target for malaria vector control. Here, we analysed the evolution of sexually-transferred steroids and their effects on female reproductive traits across Anopheles by using a set of 16 mosquito species (5 Anopheles, 8 Cellia, and 3 Nyssorhynchus), including malaria vector and non-vector species. We show that male steroid production and transfer are specific to the Cellia subgenus and that there is no correlation between mating-induced effects in females and sexually-transferred steroids. In the light of our results, male steroid production, transfer and post-mating effects in females do not correlate with their ability to transmit human malaria, which overturns the suggestion from previous studies and suggests that manipulation of steroid-response pathways in the field should be considered with caution in order to benefit malaria vector control strategies.

evolutionary biology↗