Life history effects on neutral diversity levels of autosomes and sex chromosomes, pp. 1133–1142
Guy Amster and Guy Sella
Understanding the determinants of neutral diversity patterns on autosomes and sex chromosomes provides a bedrock for our interpretation of population genetic data. Sex-specific age-structure and variation in reproductive success have long been thought to affect neutral diversity, but theoretical descriptions of these effects were complicated and/or lacked in generality, stymying attempts to relate diversity patterns of species with their life history. Amster and Sella derive general yet simple expressions for these effects, which clarify how they impact neutral diversity and should enable studies of relative diversity levels on the autosomes and sex chromosomes in many taxa.
Tolerance to hypoxia is promoted by FOXO regulation of the innate immunity transcription factor NF-κB/relish in Drosophila, pp. 1013–1025
Elizabeth C. Barretto, Danielle M. Polan, Amy N. Beevor-Potts, Byoungchun Lee, and Savraj S. Grewal
Our cells and organs need oxygen from the air we breathe in order to survive. However, although air contains twenty percent oxygen, our cells are exposed to much lower levels. In addition, our cells are often deprived of oxygen in diseases such as stroke, heart disease, and cancer. This lack of oxygen, known as hypoxia, leads to the tissue damage seen in these diseases. An important challenge in biology is to understand how cells and organs can respond to, and cope with, low oxygen. Barretto et al. identified activation of the transcription factor FOXO as a key mechanism flies use to promote survival in low oxygen. In addition, they show that one way that FOXO works is by activating Relish, a factor known to be important for immune responses. Hence, their work demonstrates that organisms may cope with low oxygen conditions by co-opting immune-like responses.
A transcriptional regulatory map of iron homeostasis reveals a new control circuit for capsule formation in Cryptococcus neoformans, pp. 1171–1189
Eunsoo Do, Yong-Joon Cho, Donghyeun Kim, James Kronstad, and Won Hee Jung
To overcome host iron restriction, the human fungal pathogen Cryptococcus neoformans uses several iron uptake mechanisms to cause disease. In this study, Do et al. used ChIP-seq and RNA-seq analysis to identify genes directly regulated by Cir1 and HapX. They identified the genes that are downstream targets of each protein and constructed comprehensive genome wide-transcriptional regulatory networks in response to iron availability. In addition, they found that Cir1 and HapX are iron-binding proteins suggesting that iron may directly influence the activities of these proteins. Together, their data provide new insights into the regulatory networks for iron acquisition and homeostasis in C. neoformans.
Systematic humanization of the yeast cytoskeleton discerns functionally replaceable from divergent human genes, pp. 1153–1169
Riddhiman K. Garge, Jon M. Laurent, Aashiq H. Kachroo, and Edward M. Marcotte
To understand the extent of functional divergence across duplicated genes in core eukaryotic systems, Garge et al. systematically tested ∼81% of human orthologs (comprising 89 new complementation pairs) across 7 major cytoskeletal gene families via simple growth rescue assays. In all, the authors found that ∼26% of tested human genes across 5 of 7 cytoskeletal families could complement their yeast equivalents. Probing functional complementation in more detail, they found varying extents to which human orthologs functionally rescue yeast cytoskeletal family-specific roles, including cell morphology, meiosis, and mating. Such cases complementation assays now provide yeast-based reagents to better understand human cytoskeletal gene function.
Spontaneous tumor regression in Tasmanian devils associated with RASL11A activation, pp. 1143–1152
Mark J. Margres, Manuel Ruiz-Aravena, Rodrigo Hamede, Kusum Chawla, Austin Patton, Matthew F. Lawrance, Alexandra K. Fraik, Amanda R. Stahlke, Brian W. Davis, Elaine A. Ostrander, Menna E. Jones, Hamish McCallum, Patrick J. Paddison, Paul A. Hohenlohe, David Hockenbery, and Andrew Storfer
Spontaneous cancer regression in humans is uncommon, but understanding the mechanisms is key for advancing treatment. Using Devil Facial Tumor Disease as a model, Margres et al. employed comparative and functional genomics to study rare instances of tumor regression in wild Tasmanian devils. The authors identified a single mutation that differed between regressed and non-regressed tumors that activated the expression of RASL11A. Inducement of RASL11A expression significantly reduced tumor growth rates in vitro. RASL11A is also under-expressed in human prostate and colon cancer. Their work suggests that RASL11A could be used as gene therapy treatment for human cancers and the Tasmanian devil.
Potassium channel-associated bioelectricity of the dermomyotome determines fin patterning in zebrafish, pp. 1067–1084
Martin R. Silic, Qiuyu Wu, Brian H. Kim, Greg Golling, Kenny H. Chen, Renata Freitas, Alexander A. Chubykin, Suresh K. Mittal, and GuangJun Zhang
It has long been recognized that the morphological complexity of vertebrates is established by spatially- and temporally-regulated cell signaling. For decades, studies of the molecular mechanisms of body patterning have focused on conserved signaling molecules and transcription factors, which has led to major insights into how the embryo is patterned. However, the roles of bioelectric signaling in developmental patterning remain largely unknown. In this paper, Silic et al. identify a potassium channel-based bioelectric signaling mechanism that regulates fin size in zebrafish. In addition, they provide the first evidence that fin size is determined by dermomyotome bioelectric properties.
Spontaneous polyploids and antimutators compete during the evolution of Saccharomyces cerevisiae mutator cells, pp. 959–974
Maxwell A. Tracy, Mitchell B. Lee, Brady L. Hearn, Ian T. Dowsett, Luke C. Thurber, Jason Loo, Anisha M. Loeb, Kent Preston, Miles I. Tuncel, Niloufar Ghodsian, Anna Bode, Thao T. Tang, Andy R. Chia, and Alan J. Herr
“Mutator” tumor cells that cannot correct DNA replication errors exhibit an extremely high mutation rate that accelerates their evolution. But this gamble puts them at risk for extinction. Haploid mutator yeast escape this problem through genome duplication, which buffers cells from lethal mutations, or “antimutator” alleles that lower mutation rate. Tracy et al. modeled mutator-driven tumors facing extinction using diploid yeast. Tetraploids arose with a 1% frequency, while the rest acquired antimutator mutations. With diploids that model heterozygous POLE mutator alleles found in cancer, cultures had many independent adapted subclones. A similar process occurring in tumors would maintain substantial intra-tumoral genetic heterogeneity.
Multi-trait genome-wide analyses of the brain imaging phenotypes in UK Biobank, pp. 947–958
Chong Wu
Wu introduced a new method termed aMAT for multi-trait analysis of any number of traits. The author conducted extensive simulations, confirming that aMAT yields well-controlled Type I error rates and achieves high statistical power across a wide range of scenarios. He then applied aMAT to GWAS summary statistics for a set of 58 volumetric imaging derived phenotypes from the UK Biobank. aMAT identified 24 distinct risk loci, 13 of which were missed by standard GWAS. Bioinformatic analyses show that the linked genes are enriched in volumetric gene sets such as hippocampal subfield CA4 volume.
In CBE — Life Sciences Education (LSE)
Diving into the details: constructing a framework of random call components, CBE—Life Sciences Education Vol. 19: doi.org/10.1187/cbe.19-07-0130
Alex H. Waugh and Tessa C. Andrews
Calling on students in class helps them engage with content, demonstrate knowledge, and foster discussion. However, research shows that asking for volunteers to answer questions often skews toward overrepresentation of male and non-minority student voices. Random call can increase the diversity of voices in the classroom, making the classroom more inclusive. Waugh and Andrews examine the factors involved in the choice of random calling and the methods to optimize its outcome. Qualitative analysis of interviews of faculty adopters highlights the costs and benefits faculty weighed and techniques deemed critical for success: 1) explain the reason for use of random call, 2) allow students to discuss the question beforehand in groups, 3) ask the question of the discussion group, and 4) be respectful and positive. Having identified these parameters, future research can now explore the relative importance of these features of random calls on positive outcomes.