The effects of genetic variants on phenotypic traits often depend on environmental and physiological conditions, but such gene-environment interactions are poorly understood. Recently developed ...approaches that treat transcript abundances of thousands of genes as quantitative traits offer the opportunity to broadly characterize the architecture of gene-environment interactions. We examined the genetic and molecular basis of variation in gene expression between two yeast strains (BY and RM) grown in two different conditions (glucose and ethanol as carbon sources). We observed that most transcripts vary by strain and condition, with 2,996, 3,448, and 2,037 transcripts showing significant strain, condition, and strain-condition interaction effects, respectively. We expression profiled over 100 segregants derived from a cross between BY and RM in both growth conditions, and identified 1,555 linkages for 1,382 transcripts that show significant gene-environment interaction. At the locus level, local linkages, which usually correspond to polymorphisms in cis-regulatory elements, tend to be more stable across conditions, such that they are more likely to show the same effect or the same direction of effect across conditions. Distant linkages, which usually correspond to polymorphisms influencing trans-acting factors, are more condition-dependent, and often show effects in different directions in the two conditions. We characterized a locus that influences expression of many growth-related transcripts, and showed that the majority of the variation is explained by polymorphism in the gene IRA2. The RM allele of IRA2 appears to inhibit Ras/PKA signaling more strongly than the BY allele, and has undergone a change in selective pressure. Our results provide a broad overview of the genetic architecture of gene-environment interactions, as well as a detailed molecular example, and lead to key insights into how the effects of different classes of regulatory variants are modulated by the environment. These observations will guide the design of studies aimed at understanding the genetic basis of complex traits.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
As soils under permanent pasture and grasslands have large topsoil carbon (C) stocks, the scope to sequester additional C may be limited. However, because C in pasture/grassland soils declines with ...depth, there may be potential to sequester additional C in the subsoil. Data from 247 continuous pasture sites in New Zealand (representing five major soil Orders and ~80% of the grassland area) showed that, on average, the 0.15–0.30 m layer contained 25–34 t ha−1 less C than the top 0.15 m. High‐production grazed pastures require periodic renewal (re‐seeding) every 7–14 years to maintain productivity. Our objective was to assess whether a one‐time pasture renewal, involving full inversion tillage (FIT) to a depth of 0.30 m, has potential to increase C storage by burying C‐rich topsoil and bringing low‐C subsoil to the surface where C inputs from pasture production are greatest. Data from the 247 pasture sites were used to model changes in C stocks following FIT pasture renewal by predicting (1) the C accumulation in the new 0–0.15 m layer and (2) the decomposition of buried‐C in the new 0.15–0.30 m layer. In the 20 years following FIT pasture renewal, soil C was predicted to increase by an average of 7.3–10.3 (Sedimentary soils) and 9.6–12.7 t C ha−1 (Allophanic soils), depending on the assumptions applied. Adoption of FIT for pasture renewal across all suitable soils (2.0–2.6 M ha) in New Zealand was predicted to sequester ~20–36 Mt C, sufficient to offset 9.6–17.5% of the country's cumulative greenhouse gas emissions from agriculture over 20 years at the current rate of emissions. Given that grasslands account for ~70% of global agricultural land, FIT renewal of pastures or grassland could offer a significant opportunity to sequester soil C and offset greenhouse gas emissions.
Soil organic C (SOC) stocks in permanent pastures and grasslands tend to be strongly stratified, being high near the surface and declining with depth. A one‐time use of full inversion tillage during pasture renewal (FIT‐PR) could increase SOC storage by burying C‐rich topsoil and bringing low‐C subsoil to the surface where C inputs from pasture are greatest. Data from New Zealand permanent pasture soils indicate the potential for FIT‐PR to increase average SOC stocks (over 20 years) in allophanic (9.6–12.7 t C ha−1) and sedimentary (7.3–10.3 t C ha−1) soils, with the amount sequestered related to pre‐renewal SOC stratification ratio.
Highlights • Gait speed is an important measure of function in older people. • A concurrent cognitive dual-task negatively impacts gait speed in healthy older adults. • Mental tracking and verbal ...fluency dual-tasks result in a significant reduction in gait speed.
Transcription controls splicing and other gene regulatory processes, yet mechanisms remain obscure due to our fragmented knowledge of the molecular connections between the dynamically phosphorylated ...RNA polymerase II (Pol II) C-terminal domain (CTD) and regulatory factors. By systematically isolating phosphorylation states of the CTD heptapeptide repeat (Y1S2P3T4S5P6S7), we identify hundreds of protein factors that are differentially enriched, revealing unappreciated connections between the Pol II CTD and co-transcriptional processes. These data uncover a role for threonine-4 in 3′ end processing through control of the transition between cleavage and termination. Furthermore, serine-5 phosphorylation seeds spliceosomal assembly immediately downstream of 3′ splice sites through a direct interaction with spliceosomal subcomplex U1. Strikingly, threonine-4 phosphorylation also impacts splicing by serving as a mark of co-transcriptional spliceosome release and ensuring efficient post-transcriptional splicing genome-wide. Thus, comprehensive Pol II interactomes identify the complex and functional connections between transcription machinery and other gene regulatory complexes.
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•Pol II phospho-CTD residues interact with unique sets of protein factors•CTD threonine-4 and Rtt103 regulate Pol II pausing after polyadenylation sites•CTD Phospho-serine-5 recruits the spliceosome and regulates splicing•CTD threonine-4 is required for efficient post-transcriptional splicing
Many RNA-processing events are coupled to transcription. To gain insight into the mechanisms linking these processes, Harlen et al. determine interactomes for each RNA polymerase II phospho-CTD residue, linking CTD Thr4 to transcription termination and CTD Thr4 and Ser5 to splicing.
Since the late nineteenth century, religiously themed books in America have been commercially popular yet scorned by critics. Working at the intersection of literary history, lived religion, and ...consumer culture, Erin A. Smith considers the largely unexplored world of popular religious books, examining the apparent tension between economic and religious imperatives for authors, publishers, and readers. Smith argues that this literature served as a form of extra-ecclesiastical ministry and credits the popularity and longevity of religious books to their day-to-day usefulness rather than their theological correctness or aesthetic quality. Drawing on publishers' records, letters by readers to authors, promotional materials, and interviews with contemporary religious-reading groups, Smith offers a comprehensive study that finds surprising overlap across the religious spectrum--Protestant, Catholic, and Jewish, liberal and conservative. Smith tells the story of how authors, publishers, and readers reconciled these books' dual function as best-selling consumer goods and spiritually edifying literature. What Would Jesus Read? will be of interest to literary and cultural historians, students in the field of print culture, and scholars of religious studies.
Bone collagen is an important material for radiocarbon, paleodietary, and paleoproteomic analyses, but it degrades over time, making such analyses more difficult with older material. Collagen ...preservation between and within archaeological sites is also variable, so that much time, effort, and money can go into the preparation and initial analysis of samples that will not yield meaningful results. To avoid this, various methods are employed to prescreen bone for collagen preservation (e.g., %N, microporosity, and FTIR spectroscopic analyses), but these are often destructive and/or require exportation for analysis. Here, we explore near-infrared spectroscopy as a tool for gauging the collagen content of ground and whole bone from about 500 to 45,000 years ago. We show that a portable spectrometer's ability to quantify collagen content and classify specimens by preservation status is comparable to that of other popular prescreening methods. Moreover, near-infrared spectroscopy is non-destructive and spectra can be acquired in a few seconds.
While genetic variation at chromatin loops is relevant for human disease, the relationships between contact propensity (the probability that loci at loops physically interact), genetics, and gene ...regulation are unclear. We quantitatively interrogate these relationships by comparing Hi-C and molecular phenotype data across cell types and haplotypes. While chromatin loops consistently form across different cell types, they have subtle quantitative differences in contact frequency that are associated with larger changes in gene expression and H3K27ac. For the vast majority of loci with quantitative differences in contact frequency across haplotypes, the changes in magnitude are smaller than those across cell types; however, the proportional relationships between contact propensity, gene expression, and H3K27ac are consistent. These findings suggest that subtle changes in contact propensity have a biologically meaningful role in gene regulation and could be a mechanism by which regulatory genetic variants in loop anchors mediate effects on expression.
An increasing number of studies have shown that senescence, the functional decline in traits and increased risk of mortality with increasing age, occurs in organisms in wild populations, but there is ...a wide range of diversity in the patterns of senescence across species.
The antagonistic pleiotropy and the disposable soma theories of senescence predict that there will be life‐history trade‐offs between performance at early‐ and late‐life stages. Plants show variation in senescence patterns and thus provide an opportunity to evaluate life‐history trade‐offs and senescence. Many plant species can be easily followed demographically and their environments, resources and allocation to reproduction can be manipulated, which makes them particularly good models to address these questions.
We compared the results from 22 studies of plant senescence in the wild and compiled 20 examples of life‐history trade‐offs in plants. Some of the unique features of plants that may influence senescence patterns and trade‐offs in the wild are highlighted through the results.
We found all three age‐specific patterns: age decline, age improvement and no change with age for plants in the wild. Most species showed an age‐dependent decline in at least one trait but, even within a species, the age‐specific patterns of traits varied. Results also showed that trade‐offs vary across environments and that plants can manipulate their resource pool through increases in photosynthesis, which will influence the manifestation of trade‐offs.
We conclude that aspects of plant biology including dynamic resource pools, the impact of size, dormancy and below‐ground storage may influence both the patterns of senescence and life‐history trade‐offs. The diversity of plant life forms and life cycles provide a wealth of opportunities to experimentally study senescence in the context of life‐history trade‐offs.
A free Plain Language Summary can be found within the Supporting Information of this article.
A free Plain Language Summary can be found within the Supporting Information of this article.
In this study, we used whole-genome sequencing and gene expression profiling of 215 human induced pluripotent stem cell (iPSC) lines from different donors to identify genetic variants associated with ...RNA expression for 5,746 genes. We were able to predict causal variants for these expression quantitative trait loci (eQTLs) that disrupt transcription factor binding and validated a subset of them experimentally. We also identified copy-number variant (CNV) eQTLs, including some that appear to affect gene expression by altering the copy number of intergenic regulatory regions. In addition, we were able to identify effects on gene expression of rare genic CNVs and regulatory single-nucleotide variants and found that reactivation of gene expression on the X chromosome depends on gene chromosomal position. Our work highlights the value of iPSCs for genetic association analyses and provides a unique resource for investigating the genetic regulation of gene expression in pluripotent cells.
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•Profiling of 215 hiPSC lines enables eQTL mapping of gene expression variation•iPSC eQTLs are enriched in stem cell gene regulatory regions and affect TF binding•Copy-number eQTLs in intergenic regulatory regions also affect expression•Whole-genome sequencing highlights the influence of rare and copy-number variants
Working as part of the NextGen consortium, DeBoever et al. use whole-genome and RNA sequencing to map expression quantitative trait loci in a set of 215 human induced pluripotent stem cell lines. These genotype-expression associations provide a foundation for understanding the genetic regulation of gene expression in pluripotent cells.
We examined the microRNAs (miRNAs) expressed in chronic lymphocytic leukemia (CLL) and identified miR-150 as the most abundant, but with leukemia cell expression levels that varied among patients. ...CLL cells that expressed ζ-chain–associated protein of 70 kDa (ZAP-70) or that used unmutated immunoglobulin heavy chain variable (IGHV) genes, each had a median expression level of miR-150 that was significantly lower than that of ZAP-70–negative CLL cells or those that used mutated IGHV genes. In samples stratified for expression of miR-150, CLL cells with low-level miR-150 expressed relatively higher levels of forkhead box P1 (FOXP1) and GRB2-associated binding protein 1 (GAB1), genes with 3′ untranslated regions having evolutionary-conserved binding sites for miR-150. High-level expression of miR-150 could repress expression of these genes, which encode proteins that enhance B-cell receptor signaling, a putative CLL-growth/survival signal. Also, high-level expression of miR-150 was a significant independent predictor of longer treatment-free survival or overall survival, whereas an inverse association was observed for high-level expression of GAB1 or FOXP1 for overall survival. This study demonstrates that expression of miR-150 can influence the relative expression of GAB1 and FOXP1 and the signaling potential of the B-cell receptor, thereby possibly accounting for the noted association of expression of miR-150 and disease outcome.
•The most abundant miRNA in CLL, miR-150, is expressed at lower levels in cases with unfavorable clinicobiological markers and worse prognosis.•miR-150 regulates expression of genes encoding proteins that modulate BCR signaling in CLL.
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