Genetic Diversity Patterns and Domestication Origin of Soybean, bioRxiv, 2018-07-14
AbstractUnderstanding diversity and evolution of a crop is an essential step to implement a strategy to expand its germplasm base for crop improvement research. Samples intensively collected from Korea, which is a small but central region in the distribution geography of soybean, were genotyped to provide sufficient data to underpin genome-wide population genetic questions. After removing natural hybrids and duplicated or redundant accessions, we obtained a non-redundant set comprising 1,957 domesticated and 1,079 wild accessions to perform population structure analyses. Our analysis demonstrates that while wild soybean germplasm will require additional sampling from diverse indigenous areas to expand the germplasm base, the current domesticated soybean germplasm is saturated in terms of genetic diversity. We then showed that our genome-wide polymorphism map enabled us to detect genetic loci underling flower color, seed-coat color, and domestication syndrome. A representative soybean set consisting of 194 accessions were divided into one domesticated subpopulation and four wild subpopulations that could be traced back to their geographic collection areas. Population genomics analyses suggested that the monophyletic group of domesticated soybeans was originated in eastern Japan. The results were further substantiated by a phylogenetic tree constructed from domestication-associated single nucleotide polymorphisms identified in this study.
biorxiv plant-biology 200-500-users 2018Cold-induced epigenetic programming of the sperm enhances brown adipose tissue activity in the offspring, Nature Medicine, 2018-07-06
Recent research has focused on environmental effects that control tissue functionality and systemic metabolism. However, whether such stimuli affect human thermogenesis and body mass index (BMI) has not been explored. Here we show retrospectively that the presence of brown adipose tissue (BAT) and the season of conception are linked to BMI in humans. In mice, we demonstrate that cold exposure (CE) of males, but not females, before mating results in improved systemic metabolism and protection from diet-induced obesity of the male offspring. Integrated analyses of the DNA methylome and RNA sequencing of the sperm from male mice revealed several clusters of co-regulated differentially methylated regions (DMRs) and differentially expressed genes (DEGs), suggesting that the improved metabolic health of the offspring was due to enhanced BAT formation and increased neurogenesis. The conclusions are supported by cell-autonomous studies in the offspring that demonstrate an enhanced capacity to form mature active brown adipocytes, improved neuronal density and more norepinephrine release in BAT in response to cold stimulation. Taken together, our results indicate that in humans and in mice, seasonal or experimental CE induces an epigenetic programming of the sperm such that the offspring harbor hyperactive BAT and an improved adaptation to overnutrition and hypothermia.
nature medicine genetics 200-500-users 2018Phenotypic Age a novel signature of mortality and morbidity risk, bioRxiv, 2018-07-06
AbstractBackgroundA person’s rate of aging has important implications for hisher risk of death and disease, thus, quantifying aging using observable characteristics has important applications for clinical, basic, and observational research. We aimed to validate a novel aging measure, “Phenotypic Age”, constructed based on routine clinical chemistry measures, by assessing its applicability for differentiating risk for morbidity and mortality in both healthy and unhealthy populations of various ages.MethodsA nationally representative US sample, NHANES III, was used to derive “Phenotypic Age” based on a linear combination of chronological age and nine multi-system clinical chemistry measures, selected via cox proportional elastic net. Mortality predictions were validated using an independent sample (NHANES IV), consisting of 11,432 participants, for whom we observed a total of 871 deaths, ascertained over 12.6 year of follow-up. Proportional hazard models and ROC curves were used to evaluate predictions.ResultsPhenotypic Age was significantly associated with all-cause mortality and cause-specific mortality. These results were robust to age and sex stratification, and remained even when excluding short-term mortality. Similarly, Phenotypic Age was associated with mortality among seemingly “healthy” participants—defined as those who were disease-free and had normal BMI at baseline—as well as the oldest-old (aged 85+)—a group with high disease burden.ConclusionsPhenotypic Age is a reliable predictor of all-cause and cause-specific mortality in multiple subgroups of the population. Risk stratification by this composite measure is far superior to that of the individual measures that go into it, as well as traditional measures of health. It is able to differentiate individuals who appear healthy, who may have otherwise been missed using traditional health assessments. Further, it can differentiate risk among persons with shared disease burden. Overall, this easily measured metric may be useful in the clinical setting and facilitate secondary and tertiary prevention strategies.
biorxiv epidemiology 200-500-users 2018Systematic assessment of GFP tag position on protein localization and growth fitness in yeast, bioRxiv, 2018-07-02
AbstractWhile protein tags are ubiquitously utilized in molecular biology, they harbor the potential to interfere with functional traits of their fusion counterparts. Systematic evaluation of the effect of protein tags on localization and function would promote accurate use of tags in experimental setups. Here we examine the effect of Green Fluorescent Protein (GFP) tagging at either the N or C terminus of budding yeast proteins on localization and functionality. We use a competition-based approach to decipher the relative fitness of two strains tagged on the same protein but on opposite termini and from that infer the correct, physiological localization for each protein and the optimal position for tagging. Our study provides a first of a kind systematic assessment of the effect of tags on the functionality of proteins and provides step towards broad investigation of protein fusion libraries.Highlights<jatslist list-type=bullet><jatslist-item>Protein tags are widely used in molecular biology although they may interfere with protein function.<jatslist-item><jatslist-item>The subcellular localization of hundreds of proteins in yeast is different when tagged at the N or the C terminus.<jatslist-item><jatslist-item>A competition based assay enables systematic deciphering of correct tagging terminus for essential proteins.<jatslist-item><jatslist-item>The presented approach can be used to derive physiologically relevant tagged libraries.<jatslist-item>
biorxiv cell-biology 200-500-users 2018A deep proteome and transcriptome abundance atlas of 29 healthy human tissues, bioRxiv, 2018-06-27
AbstractGenome-, transcriptome- and proteome-wide measurements provide valuable insights into how biological systems are regulated. However, even fundamental aspects relating to which human proteins exist, where they are expressed and in which quantities are not fully understood. Therefore, we have generated a systematic, quantitative and deep proteome and transcriptome abundance atlas from 29 paired healthy human tissues from the Human Protein Atlas Project and representing human genes by 17,615 transcripts and 13,664 proteins. The analysis revealed that few proteins show truly tissue-specific expression, that vast differences between mRNA and protein quantities within and across tissues exist and that the expression levels of proteins are often more stable across tissues than those of transcripts. In addition, only ~2% of all exome and ~7% of all mRNA variants could be confidently detected at the protein level showing that proteogenomics remains challenging, requires rigorous validation using synthetic peptides and needs more sophisticated computational methods. Many uses of this resource can be envisaged ranging from the study of geneprotein expression regulation to protein biomarker specificity evaluation to name a few.
biorxiv systems-biology 200-500-users 2018Career Choice, Gender, and Mentor Impact Results of the U.S. National Postdoc Survey, bioRxiv, 2018-06-26
AbstractThe postdoctoral community is an essential component of the academic and scientific workforce. As economic and political pressures impacting these enterprises continue to change, the postdoc experience has evolved from short, focused periods of training into often multidisciplinary, extended positions with less clear outcomes. As efforts are underway to amend U.S. federally funded research policies, the paucity of postdoc data has made evaluating the impact of policy recommendations challenging. Here we present comprehensive survey results from over 7,600 postdocs based at 351 academic and non-academic U.S. institutions in 2016. In addition to demographic and salary information, we present multivariate analyses on the factors that influence postdoc career plans and mentorship satisfaction in this population. We further analyze gender dynamics and expose wage disparities and career choice differences. Academic research positions remain the predominant career choice of postdocs in the U.S., although unequally between postdocs based on gender and residency status. Receiving mentorship training during the postdoctoral period has a large, positive effect on postdoc mentorship satisfaction. Strikingly, the quality of and satisfaction with postdoc mentorship appears to also heavily influence career choice. The data presented here are the most comprehensive data on the U.S. postdoc population to date. These results provide an evidence basis for informing government and institutional policies, and establish a critical cornerstone for quantifying the effects of future legislation aimed at the academic and scientific workforce.
biorxiv scientific-communication-and-education 200-500-users 2018