Relic Challenges for Vector-Like Fermions as Connectors to a Dark Sector

New dark sectors consisting of exotic fields that couple only very feebly to the Standard Model (SM) have strong theoretical motivation and may be relevant to explaining the abundance of dark matter (DM). An important question for such sectors is how they connect to the SM. For a dark sector with a new gauge interaction, a natural connection arises from heavy vector-like fermions charged under both the visible and dark gauge groups. The gauge charges of such fermions imply that one or more of them is stable in the absence of additional sources of dark symmetry breaking. A generic challenge for such connectors is that they can produce too much dark matter or interact too strongly with nuclei if they were ever thermalized in the early universe. In this paper we study this challenge in a simple connector theory consisting of new vector-like electroweak doublet and singlet fermions that also transform under the fundamental representation of a new (Abelian) gauge force, and we show that these connectors in their minimal form are almost always ruled out by existing direct DM searches. To address this challenge, we investigate two solutions. First, we study mitigating scattering on nuclei by introducing a Majorana mass term for the singlet. And second, we investigate a mixing with SM leptons that allows the connectors to decay while remaining consistent with cosmological tests and searches for charged lepton flavor violation. Both solutions rely on the presence of a dark Higgs field with a specific charge.Comment: 32 pages, 5 figures, added references, corrected plotting error, conclusions unchange

Forward-backward asymmetry in B→D∗ℓν: One more hint for scalar leptoquarks?

Experimental data have provided intriguing hints for the violation of lepton flavor universality (LFU), including B→D(*)τν/B→D(*)ℓν, the anomalous magnetic moment of the muon and b→sℓ+ℓ− with a significance of >3σ, >4σ, and >5σ, respectively. Furthermore, in a recent reanalysis of 2018 Belle data, it was found that the forward-backward asymmetry (ΔAFB) of B→D∗μ¯ν vs B→D∗e¯ν disagrees with the SM prediction by ≈4σ, providing an additional sign of LFU violation. We show that a tensor operator is necessary to significantly improve the agreement with data in ΔAFB while respecting the bounds from other b→cℓν observables. Importantly, this tensor operator can only be induced (at tree-level within renormalizable models) by a scalar leptoquark. Furthermore, among the two possible representations, the SU(2)L-singlet S1 and the doublet S2, which can interestingly both also account for the anomalous magnetic moment of the muon, only S1 can provide a good fit. Even though the constraints from (differences of) other angular observables prefer a smaller value of ΔAFB than the current central one, this scenario is significantly preferred (nearly 4σ) over the Standard Model hypothesis, and is compatible with constraints such as B→K∗νν and electroweak precision bounds. Therefore, if the ΔAFB anomaly is confirmed, it would provide circumstantial evidence for scalar leptoquarks and pave the way for a natural connection with all other anomalies pointing toward LFU violation

The Recalcitrance and Resilience of Scientific Function

“Function” is a vitally important concept in the scientific community. Scientists use it to describe and address a wide variety of research problems. In publications, however, scientists within and across disciplines interpret function differently. For example, intense controversy surrounds what percentage of the human genome should be deemed "functional” rather than “junk DNA.” In this essay, we analyze the use of function in the research of de novo gene birth, a budding scientific field that studies how novel genes can emerge in non-genic sequences. Our research team, composed of a rhetorical scholar, philosopher, structural biologist and systems biologist, crafts a taxonomy of how “function” is variously constituted in de novo gene birth publications, including as expressions, capacities, interactions, physiological implications and evolutionary implications. We argue function is shaped by the diverse onto-epistemological perspectives of scientists and is both a recalcitrant and resilient concept of scientific practice. Informed by Gilles Deleuze and Felix Guattari’s writings on a scientific mode of thinking, functions are time-space scales of objects under investigation that make possible references to scientific measurements

Genome-Wide Identification of Pseudomonas aeruginosa Virulence-Related Genes Using a Caenorhabditis elegans Infection Model

Pseudomonas aeruginosa strain PA14 is an opportunistic human pathogen capable of infecting a wide range of organisms including the nematode Caenorhabditis elegans. We used a non-redundant transposon mutant library consisting of 5,850 clones corresponding to 75% of the total and approximately 80% of the non-essential PA14 ORFs to carry out a genome-wide screen for attenuation of PA14 virulence in C. elegans. We defined a functionally diverse 180 mutant set (representing 170 unique genes) necessary for normal levels of virulence that included both known and novel virulence factors. Seven previously uncharacterized virulence genes (ABC transporters PchH and PchI, aminopeptidase PepP, ATPase/molecular chaperone ClpA, cold shock domain protein PA0456, putative enoyl-CoA hydratase/isomerase PA0745, and putative transcriptional regulator PA14_27700) were characterized with respect to pigment production and motility and all but one of these mutants exhibited pleiotropic defects in addition to their avirulent phenotype. We examined the collection of genes required for normal levels of PA14 virulence with respect to occurrence in P. aeruginosa strain-specific genomic regions, location on putative and known genomic islands, and phylogenetic distribution across prokaryotes. Genes predominantly contributing to virulence in C. elegans showed neither a bias for strain-specific regions of the P. aeruginosa genome nor for putatively horizontally transferred genomic islands. Instead, within the collection of virulence-related PA14 genes, there was an overrepresentation of genes with a broad phylogenetic distribution that also occur with high frequency in many prokaryotic clades, suggesting that in aggregate the genes required for PA14 virulence in C. elegans are biased towards evolutionarily conserved genes

The life cycle of Drosophila orphan genes

Orphans are genes restricted to a single phylogenetic lineage and emerge at high rates. While this predicts an accumulation of genes, the gene number has remained remarkably constant through evolution. This paradox has not yet been resolved. Because orphan genes have been mainly analyzed over long evolutionary time scales, orphan loss has remained unexplored. Here we study the patterns of orphan turnover among close relatives in the Drosophila obscura group. We show that orphans are not only emerging at a high rate, but that they are also rapidly lost. Interestingly, recently emerged orphans are more likely to be lost than older ones. Furthermore, highly expressed orphans with a strong male-bias are more likely to be retained. Since both lost and retained orphans show similar evolutionary signatures of functional conservation, we propose that orphan loss is not driven by high rates of sequence evolution, but reflects lineage specific functional requirements.Comment: 47 pages, 19 figure

Reinforcing the Egg-Timer: Recruitment of Novel Lophotrochozoa Homeobox Genes to Early and Late Development in the Pacific Oyster

The metazoan superclade Lophotrochozoa includes mollusks, annelids, and several other animal phyla. It is reasonable to assume that this organismal diversity may be traced, in part, to changes in developmentally important genes, such as the homeobox genes. Although most comparative studies have focussed on ancient homeobox gene families conserved across bilaterians, there are also "novel" homeobox genes that have arisen more recently in evolution, presumably by duplication followed by radical divergence and functional change. We classify 136 homeobox genes in the genome sequence of the Pacific oyster, Crassostrea gigas. The genome shows an unusually low degree of homeobox gene clustering, with disruption of the NK, Hox, and ParaHox gene clusters. Among the oyster genes, 31 do not fall into ancient metazoan or bilaterian homeobox gene families; we deduce that they originated in the lophotrochozoan clade. We compared eight lophotrochozoan genomes to trace the pattern of homeobox gene evolution across this clade, allowing us to define 19 new lophotrochozoan-specific clades within the ANTP, PRD, TALE, ZF, SIX, and CUT classes. Using transcriptome data, we compared temporal expression of each homeobox gene in oyster development, and discovered that the lophotrochozoan-specific homeobox genes have peak expression either in early development (egg to gastrula) or in late development (after the trochophore larval stage), but rarely in between. This finding is consistent with the egg-timer, hourglass or phylotypic stage model of developmental evolution, in which there is a conserved central phase of development, but more evolutionarily labile early and late phases

Interpreting Cancer Genomes Using Systematic Host Perturbations by Tumour Virus Proteins

Genotypic differences greatly influence susceptibility and resistance to disease. Understanding genotype-phenotype relationships requires that phenotypes be viewed as manifestations of network properties, rather than simply as the result of individual genomic variations. Genome sequencing efforts have identified numerous germline mutations associated with cancer predisposition and large numbers of somatic genomic alterations. However, it remains challenging to distinguish between background, or “passenger” and causal, or “driver” cancer mutations in these datasets. Human viruses intrinsically depend on their host cell during the course of infection and can elicit pathological phenotypes similar to those arising from mutations. To test the hypothesis that genomic variations and tumour viruses may cause cancer via related mechanisms, we systematically examined host interactome and transcriptome network perturbations caused by DNA tumour virus proteins. The resulting integrated viral perturbation data reflects rewiring of the host cell networks, and highlights pathways that go awry in cancer, such as Notch signalling and apoptosis. We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on par with their identification through functional genomics and large-scale cataloguing of tumour mutations. Together, these complementary approaches result in increased specificity for cancer gene identification. Combining systems-level studies of pathogen-encoded gene products with genomic approaches will facilitate prioritization of cancer-causing driver genes so as to advance understanding of the genetic basis of human cancer

Classification and function of small open reading frames

Small open reading frames (smORFs) of 100 codons or fewer are usually - if arbitrarily - excluded from proteome annotations. Despite this, the genomes of many metazoans, including humans, contain millions of smORFs, some of which fulfil key physiological functions. Recently, the transcriptome of Drosophila melanogaster was shown to contain thousands of smORFs of different classes that actively undergo translation, which produces peptides of mostly unknown function. Here, we present a comprehensive analysis of smORFs in flies, mice and humans. We propose the existence of several functional classes of smORFs, ranging from inert DNA sequences to transcribed and translated cis-regulators of translation and peptides with a propensity to function as regulators of membrane-associated proteins, or as components of ancient protein complexes in the cytoplasm. We suggest that the different smORF classes could represent steps in gene, peptide and protein evolution. Our analysis introduces a distinction between different peptide-coding classes of smORFs in animal genomes, and highlights the role of model organisms for the study of small peptide biology in the context of development, physiology and human disease

Transcriptomic profiling of host-parasite interactions in the microsporidian <i>Trachipleistophora hominis</i>

BACKGROUND: Trachipleistophora hominis was isolated from an HIV/AIDS patient and is a member of a highly successful group of obligate intracellular parasites. METHODS: Here we have investigated the evolution of the parasite and the interplay between host and parasite gene expression using transcriptomics of T. hominis-infected rabbit kidney cells. RESULTS: T. hominis has about 30 % more genes than small-genome microsporidians. Highly expressed genes include those involved in growth, replication, defence against oxidative stress, and a large fraction of uncharacterised genes. Chaperones are also highly expressed and may buffer the deleterious effects of the large number of non-synonymous mutations observed in essential T. hominis genes. Host expression suggests a general cellular shutdown upon infection, but ATP, amino sugar and nucleotide sugar production appear enhanced, potentially providing the parasite with substrates it cannot make itself. Expression divergence of duplicated genes, including transporters used to acquire host metabolites, demonstrates ongoing functional diversification during microsporidian evolution. We identified overlapping transcription at more than 100 loci in the sparse T. hominis genome, demonstrating that this feature is not caused by genome compaction. The detection of additional transposons of insect origin strongly suggests that the natural host for T. hominis is an insect. CONCLUSIONS: Our results reveal that the evolution of contemporary microsporidian genomes is highly dynamic and innovative. Moreover, highly expressed T. hominis genes of unknown function include a cohort that are shared among all microsporidians, indicating that some strongly conserved features of the biology of these enormously successful parasites remain uncharacterised. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12864-015-1989-z) contains supplementary material, which is available to authorized users