PNAS Plus Significance Statements

Abstract

Pasta and bread wheat are polyploid species that carry multiple copies of each gene. Therefore, loss-offunction mutations in one gene copy are frequently masked by functional copies on other genomes. We sequenced the protein coding regions of 2,735 mutant lines and developed a public database including more than 10 million mutations. Researchers and breeders can search this database online, identify mutations in the different copies of their target gene, and request seeds to study gene function or improve wheat varieties. Mutations are being used to improve the nutritional value of wheat, increase the size of the wheat grains, and generate additional variability in flowering genes to improve wheat adaptation to new and changing environments. Our Girvan-Newman-based community network analysis provides a strategy to explore the effects of protein kinase mutations on the dynamic properties of the kinase core and the allosteric network underlying the catalytic cycle. With this approach, which allows us to identify subtle shifts in dynamics and in particular side-chain rotamer preferences, we can explain the underlying mechanism for loss of function in many different scenarios. Our method is especially relevant for disease-causing mutations that lie far from the active site but show no obvious structural perturbations based on X-ray crystallography. (See pp. E931-E940.)Heat-induced masculinization in domesticated zebrafish is family-specific and yields a set of different gonadal transcriptomes Laia Ribas, Woei Chang Liew, Noèlia Díaz, Rajini Sreenivasan, László Orbán, and Francesc Piferrer Fish exhibit remarkable sexual plasticity. However, the underlying mechanism of heat-induced sex reversal is still unclear. Here we first established the conditions for heat-induced reprogramming of sexual phenotypes in zebrafish through sex ratio analysis and gonad transcriptomics. Sex ratio response to heat was family-specific and resulted in masculinization. We observed two heat-induced gonadal transcriptomic profiles per sex in adults, among them neomales and, strikingly, females with an ovary but a "male-like" transcriptome. The latter indicates major transcriptomic reprogramming with preserved organ structure, an interesting observation in vertebrates. In all heat-treated juveniles, we also observed a male-like transcriptome. Overall, this study reveals novel lasting thermal effects on fish gonads, with practical implications for studying the effects of global warming in natural populations. (See pp. E941-E950.) Similarities and differences in the transcriptional control of expression of the mouse TSLP gene in skin epidermis and intestinal epithelium Krishna Priya Ganti, Atish Mukherji, Milan Surjit, Mei Li, and Pierre Chambon Thymic stromal lymphopoietin (TSLP) is a critical immunoregulatory cytokine that plays important physiological functions in epithelial cells in skin and intestinal barriers. However, the molecular mechanisms controlling TSLP expression in vivo are still poorly understood. Using tissue-selective mutagene...