Emerging Properties and Functional Consequences of Noncoding Transcription [Perspectives]
Eukaryotic genomes are rich in transcription units encoding "long noncoding RNAs" (lncRNAs). The purpose of all this transcription is unclear since most lncRNAs are quickly targeted for destruction during synthesis or shortly thereafter. As debates continue over the functional significance of many specific lncRNAs, support grows for the notion that the act of transcription rather than the RNA product itself is functionally important in many cases. Indeed, this alternative mechanism might better explain how low-abundance lncRNAs transcribed from noncoding DNA function in organisms. Here, we highlight some of the recently em...
Source: Genetics - October 4, 2017 Category: Genetics & Stem Cells Authors: Ard, R., Allshire, R. C., Marquardt, S. Tags: Perspectives Source Type: research
ISSUE HIGHLIGHTS [Issue Highlights]
(Source: Genetics)
Source: Genetics - October 4, 2017 Category: Genetics & Stem Cells Tags: Issue Highlights Source Type: research
Histone Acetylation, Not Stoichiometry, Regulates Linker Histone Binding in Saccharomyces cerevisiae [Genome and Systems Biology]
In this study, we used a combination of genetic and genomic approaches to explore the regulation of linker histone binding in the yeast, Saccharomyces cerevisiae. We found that increased expression of Hho1, the yeast linker histone, resulted in a severe growth defect, despite only subtle changes in chromatin structure. Further, this growth defect was rescued by mutations that increase histone acetylation. Consistent with this, genome-wide analysis of linker histone occupancy revealed an inverse correlation with histone tail acetylation in both yeast and mouse embryonic stem cells. Collectively, these results suggest that h...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Lawrence, M. B. D., Coutin, N., Choi, J. K., Martin, B. J. E., Irwin, N. A. T., Young, B., Loewen, C., Howe, L. J. Tags: Genome and Systems Biology Source Type: research
Tracing Genetic Exchange and Biogeography of Cryptococcus neoformans var. grubii at the Global Population Level [Genome and Systems Biology]
Cryptococcus neoformans var. grubii is the causative agent of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals, typically human immunodeficiency virus/AIDS patients from developing countries. Despite the worldwide emergence of this ubiquitous infection, little is known about the global molecular epidemiology of this fungal pathogen. Here we sequence the genomes of 188 diverse isolates and characterize the major subdivisions, their relative diversity, and the level of genetic exchange between them. While most isolates of C. neoformans var. grubii belong to one of three major lineag...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Rhodes, J., Desjardins, C. A., Sykes, S. M., Beale, M. A., Vanhove, M., Sakthikumar, S., Chen, Y., Gujja, S., Saif, S., Chowdhary, A., Lawson, D. J., Ponzio, V., Colombo, A. L., Meyer, W., Engelthaler, D. M., Hagen, F., Illnait-Zaragozi, M. T., Alanio, A. Tags: Genome and Systems Biology Source Type: research
Naturally Segregating Variation at Ugt86Dd Contributes to Nicotine Resistance in Drosophila melanogaster [Genetics of Complex Traits]
Identifying the sequence polymorphisms underlying complex trait variation is a key goal of genetics research, since knowing the precise causative molecular events allows insight into the pathways governing trait variation. Genetic analysis of complex traits in model systems regularly starts by constructing QTL maps, but generally fails to identify causative sequence polymorphisms. Previously we mapped a series of QTL contributing to resistance to nicotine in a Drosophila melanogaster multiparental mapping resource and here use a battery of functional tests to resolve QTL to the molecular level. One large-effect QTL resided...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Highfill, C. A., Tran, J. H., Nguyen, S. K. T., Moldenhauer, T. R., Wang, X., Macdonald, S. J. Tags: Genetics of Complex Traits Source Type: research
The Recombination Landscape in Wild House Mice Inferred Using Population Genomic Data [Population and Evolutionary Genetics]
In this study, we constructed fine-scale recombination rate maps for a natural population of the Eastern house mouse, Mus musculus castaneus. We performed simulations to assess the accuracy of recombination rate inference in the presence of phase errors, and we used a novel approach to quantify phase error. The spatial distribution of recombination events is strongly positively correlated between our castaneus map, and a map constructed using inbred lines derived predominantly from M. m. domesticus. Recombination hotspots in wild castaneus show little overlap, however, with the locations of double-strand breaks in wild-der...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Booker, T. R., Ness, R. W., Keightley, P. D. Tags: Population and Evolutionary Genetics Source Type: research
Recombination-Driven Genome Evolution and Stability of Bacterial Species [Population and Evolutionary Genetics]
While bacteria divide clonally, horizontal gene transfer followed by homologous recombination is now recognized as an important contributor to their evolution. However, the details of how the competition between clonality and recombination shapes genome diversity remains poorly understood. Using a computational model, we find two principal regimes in bacterial evolution and identify two composite parameters that dictate the evolutionary fate of bacterial species. In the divergent regime, characterized by either a low recombination frequency or strict barriers to recombination, cohesion due to recombination is not sufficien...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Dixit, P. D., Pang, T. Y., Maslov, S. Tags: Population and Evolutionary Genetics Source Type: research
Untangling Heteroplasmy, Structure, and Evolution of an Atypical Mitochondrial Genome by PacBio Sequencing [Population and Evolutionary Genetics]
The highly compact mitochondrial (mt) genome of terrestrial isopods (Oniscidae) presents two unusual features. First, several loci can individually encode two tRNAs, thanks to single nucleotide polymorphisms at anticodon sites. Within-individual variation (heteroplasmy) at these loci is thought to have been maintained for millions of years because individuals that do not carry all tRNA genes die, resulting in strong balancing selection. Second, the oniscid mtDNA genome comes in two conformations: a ~14 kb linear monomer and a ~28 kb circular dimer comprising two monomer units fused in palindrome. We hypothesized ...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Peccoud, J., Chebbi, M. A., Cormier, A., Moumen, B., Gilbert, C., Marcade, I., Chandler, C., Cordaux, R. Tags: Population and Evolutionary Genetics Source Type: research
Contrasting Determinants of Mutation Rates in Germline and Soma [Population and Evolutionary Genetics]
Recent studies of somatic and germline mutations have led to the identification of a number of factors that influence point mutation rates, including CpG methylation, expression levels, replication timing, and GC content. Intriguingly, some of the effects appear to differ between soma and germline: in particular, whereas mutation rates have been reported to decrease with expression levels in tumors, no clear effect has been detected in the germline. Distinct approaches were taken to analyze the data, however, so it is hard to know whether these apparent differences are real. To enable a cleaner comparison, we considered a ...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Chen, C., Qi, H., Shen, Y., Pickrell, J., Przeworski, M. Tags: Population and Evolutionary Genetics Source Type: research
Exact Calculation of the Joint Allele Frequency Spectrum for Isolation with Migration Models [Population and Evolutionary Genetics]
Population genomic datasets collected over the past decade have spurred interest in developing methods that can utilize massive numbers of loci for inference of demographic and selective histories of populations. The allele frequency spectrum (AFS) provides a convenient statistic for such analysis, and, accordingly, much attention has been paid to predicting theoretical expectations of the AFS under a number of different models. However, to date, exact solutions for the joint AFS of two or more populations under models of migration and divergence have not been found. Here, we present a novel Markov chain representation of ...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Kern, A. D., Hey, J. Tags: Population and Evolutionary Genetics Source Type: research
Decomposing the Site Frequency Spectrum: The Impact of Tree Topology on Neutrality Tests [Population and Evolutionary Genetics]
We present a new test for selection in the same class as Fay and Wu’s H and discuss its interpretation and power. Finally, we determine the trees corresponding to extreme expected values of these neutrality tests and present formulas for these extreme values as a function of sample size and number of segregating sites. (Source: Genetics)
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Ferretti, L., Ledda, A., Wiehe, T., Achaz, G., Ramos-Onsins, S. E. Tags: Population and Evolutionary Genetics Source Type: research
A Gene Implicated in Activation of Retinoic Acid Receptor Targets Is a Novel Renal Agenesis Gene in Humans [Developmental and Behavioral Genetics]
This study is the first to associate a component of the RAR pathway with renal agenesis in humans. (Source: Genetics)
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Brophy, P. D., Rasmussen, M., Parida, M., Bonde, G., Darbro, B. W., Hong, X., Clarke, J. C., Peterson, K. A., Denegre, J., Schneider, M., Sussman, C. R., Sunde, L., Lildballe, D. L., Hertz, J. M., Cornell, R. A., Murray, S. A., Manak, J. R. Tags: Developmental and Behavioral Genetics Source Type: research
Noncanonical Decapentaplegic Signaling Activates Matrix Metalloproteinase 1 To Restrict Hedgehog Activity and Limit Ectopic Eye Differentiation in Drosophila [Developmental and Behavioral Genetics]
One of the pertinent issues associated with cellular plasticity is to understand how the delicate balance between the determined state of cells and the extent to which they can transdetermine is maintained. Employing the well-established model of generating ectopic eyes in developing wing discs of Drosophila by ectopic eyeless expression, we provide evidence for the genetic basis of this mechanism. By both loss-of-function and gain-of-function genetic analyses, we demonstrate that Matrix metalloproteinase 1 (Mmp1) plays an important role in regulating the extent of ectopic ommatidial differentiation. Transcriptional activa...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Aggarwal, P., Gera, J., Ghosh, S., Mandal, L., Mandal, S. Tags: Developmental and Behavioral Genetics Source Type: research
The Stress-Sensing TORC2 Complex Activates Yeast AGC-Family Protein Kinase Ypk1 at Multiple Novel Sites [Cellular Genetics]
Yeast (Saccharomyces cerevisiae) target of rapamycin (TOR) complex 2 (TORC2) is a multi-subunit plasma membrane-associated protein kinase and vital growth regulator. Its essential functions are exerted via phosphorylation and stimulation of downstream protein kinase Ypk1 (and its paralog Ypk2). Ypk1 phosphorylates multiple substrates to regulate plasma membrane lipid and protein composition. Ypk1 function requires phosphorylation of Thr504 in its activation loop by eisosome-associated Pkh1 (and its paralog Pkh2). For cell survival under certain stresses, however, Ypk1 activity requires further stimulation by TORC2-mediated...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Leskoske, K. L., Roelants, F. M., Marshall, M. N. M., Hill, J. M., Thorner, J. Tags: Cellular Genetics Source Type: research
MicroRNAs That Contribute to Coordinating the Immune Response in Drosophila melanogaster [Genetics of Immunity]
Small noncoding RNAs called microRNAs (miRNAs) have emerged as post-transcriptional regulators of gene expression related to host defenses. Here, we have used Drosophila melanogaster to explore the contribution of individual or clusters of miRNAs in countering systemic Candida albicans infection. From a total of 72 tested, we identify 6 miRNA allelic mutant backgrounds that modulate the survival response to infection and the ability to control pathogen number. These mutants also exhibit dysregulation of the Toll pathway target transcripts Drosomycin (Drs) and Immune-Induced Molecule 1 (IM1). These are characteristics of de...
Source: Genetics - September 5, 2017 Category: Genetics & Stem Cells Authors: Atilano, M. L., Glittenberg, M., Monteiro, A., Copley, R. R., Ligoxygakis, P. Tags: Genetics of Immunity Source Type: research
