This Month’s Centennial Articles
The sustained impact of model organisms—in genetics and epigenetics, pp. 1-4
Nancy M. Bonini and Shelley L. Berger
In this GENETICS Centennial commentary, Nancy M. Bonini and Shelley L. Berger reflect on the history of genetic research on model organisms and whether these models will continue to play important roles in uncovering mechanisms of basic biological processes.
Coordination of cell cycle progression and mitotic spindle assembly involves histone H3 lysine 4 methylation by Setl/COMPASS, pp. 185-199
Traude H. Beilharz, Paul F. Harrison, Douglas Maya Miles, Michael Ming See, Uyen Minh Merry Le, Ming Kalanon, Melissa Jane Curtis, Qambar Hasan, Julie Saksouk, Thanasis Margaritis, Frank Holstege, Vincent Geli, and Bernhard Dichtl
The biological functions of H3K4 methylation by the Setl complex remain unclear. Beilharz et al. found the chromatin mark is needed for normal transcription levels and timing during the cell-cycle. Notably, Setl is required for proper tubulin expression. H3K4 meth- ylation deficient cells display resistance to the microtubule destabilizing drug benomyl, have delayed entry into S-phase, and reveal a genetic interaction with the aurora kinase component of the spindle assembly checkpoint. Thus, H3K4 methylation is important for coordinating early cell cycle phases with chromosome segregation during mitosis.
Controlling the rate of GWAS false discoveries, pp. 61-75
Damian Brzyski, Christine B. Peterson, Piotr Sobczyk, Emmanuel J. Candes, Malgorzata Bogdan, and Chiara Sabatti
Controlling the false discovery rate (FDR) has become increasingly appealing and accepted for multiple comparison adjustment in genetic association studies. Brzyski et al. illustrate the challenges presented by linkage disequilibrium for methods that target FDR and show how to overcome these issues using a novel selective approach. They also show how a recently introduced penalized estimation approach allows simultaneous, accurate identification of multiple loci influencing a trait.
Variation and evolution of the meiotic requirement for crossing over in mammals, pp. 155-168
Beth L. Dumont
To correctly segregate homologs at meiosis, do mammals require one crossover per chromosome or one crossover per chromosome arm? To address this fundamental question, Dumont measured recombination in karyotypically diverse house mice and voles. Intriguingly, the recombination patterns revealed species-level variation in the chromosomal constraint on crossing over. Phylogenetic analyses of published recombination and karyotype data uncovered evidence for multiple independent shifts in the apparent scale of the chromosomal demand for crossing over at meiosis during mammalian evolution.
Survey of global genetic diversity within the Drosophila immune system, pp. 353-366
Angela M. Early, J. Roman Arguello, Margarida Cardoso-Moreira, Srikanth Gottipati, Jennifer K. Grenier, and Andrew G. Clark
Immune genes are among the most rapidly evolving in a wide range of taxa. This does not imply, however, that all immune genes experience rapid adaptation. Early et al. surveyed immune genes in fruit fly populations and show that strong selection on these genes is not pervasive. Further, the flies displayed similar responses to bacterial infection regardless of their geographic origin. These results imply that the innate immune response is relatively robust and may not require extensive “fine-tuning” when confronting new environments and pathogens.
Inferring heterozygosity from ancient and low coverage genomes, pp. 317-332
Athanasios Kousathanas, Christoph Leuenberger, Vivian Link, Christian Sell, Joachim Burger, and Daniel Wegmann
Kousathanas et al. introduce a novel method to infer genetic diversity from very low coverage data of a single individual. They further introduce a method to recalibrate quality scores from sequencing machines. Importantly, neither method requires a reference genome except for the initial alignment of the data. Applying these new methods to ancient human samples revealed substantial differences between European hunter-gatherer samples, suggesting the European population was highly structured prior to the arrival of farming.
Complex ancient genetic structure and cultural transitions in southern African populations, pp. 303-316
Francesco Montinaro, George B. J. Busby, Miguel Gonzalez-Santos, Ockie Oosthuitzen, Erika Oosthuitzen, Paolo Anagnostou, Giovanni Destro-Bisol, Vincenzo L. Pascali, and Cristian Capelli
Southern Africa is characterized by extraordinary anthropological and linguistic variation. Archaeological records document the presence of distinct Hunter-gatherer and Khoesan-speaking groups before the arrival of Bantu-speaking and European settlers. Using local ancestry analyses Montinaro et al. identify a tripartite, ancient, Khoesan genetic structure that correlates with geography, but not with linguistic affiliation or subsistence strategy. Fine mapping revealed admixture dynamics and episodes of cultural reversion involving several southern African groups.
Stage-specific timing of the microRNA regulation of lin-28 by the heterochronic gene lin-14 in Caenorhabditis elegans, pp. 251-262
Jennifer Tsialikas, Mitchell A. Romens, Allison Abbott, and Eric G. Moss
Developmental timing in Caenorhabditis elegans is controlled by the heterochronic pathway, a complex network of proteins and microRNAs. These act in feedforward and feedback interactions to form a robust mechanism for the stage-specific timing of development. The RNA binding protein LIN-28 is positively regulated by LIN-14 but the mechanism was previously unknown. Tsialikas et al. demonstrate that three let-7-family and one lin-4-family microRNAs negatively regulate lin-28 and are directly inhibited by LIN-14 activity, making them the first known targets of LIN-14 that act in the heterochronic pathway.
Widespread historical contingency in influenza viruses, pp. 409-420
Jean Claude Nshogozabahizi, Jonathan Dench, and Stephane Aris-Brosou
Detecting epistasis in sequence data is challenging. Nshogozabahizi et al. use a classical approach for detecting coevolution of binary characters on a phylogeny. They carry out extensive simulations to test the statistical properties of this method, further validate it against experimental data, and apply it to five influenza virus data sets. The authors show that epistasis is widespread among these viruses and takes the form of networks of correlated sites.