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Rare variants contribute disproportionately to quantitative trait variation in yeast.
How variants with different frequencies contribute to trait variation is a central question in genetics. We use a unique model system to disentangle the contributions of common and rare variants to quantitative traits. We generated ~14,000 progeny from crosses among 16 diverse yeast strains and identified thousands of quantitative trait loci (QTLs) for 38 traits. We combined our results with sequencing data for 1011 yeast isolates to show that rare variants make a disproportionate contribution to trait variation. Evolutionary analyses revealed that this contribution is driven by rare variants that arose recently, and that negative selection has shaped the relationship between variant frequency and effect size. We leveraged the structure of the crosses to resolve hundreds of QTLs to single genes. These results refine our understanding of trait variation at the population level and suggest that studies of rare variants are a fertile ground for discovery of genetic effects
Hydrothermal recycling of sedimentary ammonium into oceanic crust and the Archean ocean at 3.24 Ga
Funding was provided by a Natural Environment Research Council studentship (grant NE/R012253/1) to T.J. Boocock, and a National Science Foundation grant (grant EARPF 1725784) and an American Philosophical Society Lewis and Clark Grant, both to B.W. Johnson.The Archean ocean supported a diverse microbial ecosystem, yet studies suggest that seawater was largely depleted in many essential nutrients, including fixed nitrogen. This depletion was in part a consequence of inefficient nutrient recycling under anoxic conditions. Here, we show how hydrothermal fluids acted as a recycling mechanism for ammonium (NH4+) in the Archean ocean. We present elemental and stable isotope data for carbon, nitrogen, and sulfur from shales and hydrothermally altered volcanic rocks from the 3.24 Ga Panorama district in Western Australia. This suite documents the transfer of NH4+ from organic-rich sedimentary rocks into underlying sericitized dacite, similar to what is seen in hydrothermal systems today. On modern Earth, hydrothermal fluids that circulate through sediment packages are enriched in NH4+ to millimolar concentrations because they efficiently recycle organic-bound N. Our data show that a similar hydrothermal recycling process dates back to at least 3.24 Ga, and it may have resulted in localized centers of enhanced biological productivity around hydrothermal vents. Last, our data provide evidence that altered oceanic crust at 3.24 Ga was enriched in nitrogen, and, when subducted, it satisfies the elemental and isotopic source requirements for a low-N, but 15N-enriched, deep mantle nitrogen reservoir as sampled by mantle plumes.PostprintPeer reviewe
Equilibrium partitioning and isotopic fractionation of nitrogen between biotite, plagioclase, and K-feldspar during magmatic differentiation
Funding: UK Natural Environment Research Council (NE/R012253/1, NE/V010824/1, NE/P012167/1)A significant portion of the continental crust is composed of plutonic igneous rocks. However, little is known about the geochemical behaviour of N between the different minerals during magmatic differentiation. To provide new constraints for the behaviour of N during crust formation, we have characterised the geochemistry of nitrogen (N) in the compositionally zoned calc-alkaline pluton at Loch Doon, SW Scotland. We present N concentration and N isotope values for whole-rock data alongside biotite, plagioclase and K-feldspar mineral separates and assess the degree to which these data preserve equilibrium partitioning during magmatic differentiation. We show that whole rock likely inherited its N contents and ÎŽ15N signatures from the initial source composition and that this signature is homogenous at a pluton scale. Whilst the whole-rock data are best explained as crust-derived N in the source, the degree of homogenisation across a pluton scale is inconsistent with empirical N diffusivities, ruling out syn-emplacement crustal assimilation as the source of N. Instead, our data suggest a crustal signature inherited from depth associated with the Iapetus subduction zone. At a mineral scale, we find that N preferentially partitions into the feldspars over mica in this system in the order K-feldspar > plagioclase â biotite > quartz, with average mineral-mineral distribution coefficients of DNplagioclase-biotite = 1.3 ± 0.6 and DNKspar-biotite = 2.8 ± 0.6. Partitioning is accompanied by a large and near constant equilibrium isotope fractionation factor between biotite and both feldspars (averages are Î15NPlag-Biotite = +7.8 ± 1.2 â° and Î15NKspar-Biotite = +7.9 ± 1.0 â°), whereas Î15NKspar-Plagioclase closely approximates 0 â°, where both minerals show ÎŽ15N overlapping with the bulk rock ÎŽ15N values. These results show that mica crystallisation generates in a large negative Î15N resulting a 15N-depleted reservoir within plutonic rocks. Moreover, our dataset suggests that feldspars might be a more significant host of N in the igneous portion of Earthâs continental and oceanic crust than previous thought.Publisher PDFPeer reviewe
Nicked-site substrates for a serine recombinase reveal enzyme-DNA communications and an essential tethering role of covalent enzyme-DNA linkages
To analyse the mechanism and kinetics of DNA strand cleavages catalysed by the serine recombinase Tn3 resolvase, we made modified recombination sites with a single-strand nick in one of the two DNA strands. Resolvase acting on these sites cleaves the intact strand very rapidly, giving an abnormal half-site product which accumulates. We propose that these reactions mimic second-strand cleavage of an unmodified site. Cleavage occurs in a synapse of two sites, held together by a resolvase tetramer; cleavage at one site stimulates cleavage at the partner site. After cleavage of a nicked-site substrate, the half-site that is not covalently linked to a resolvase subunit dissociates rapidly from the synapse, destabilizing the entire complex. The covalent resolvaseâDNA linkages in the natural reaction intermediate thus perform an essential DNA-tethering function. Chemical modifications of a nicked-site substrate at the positions of the scissile phosphodiesters result in abolition or inhibition of resolvase-mediated cleavage and effects on resolvase binding and synapsis, providing insight into the serine recombinase catalytic mechanism and how resolvase interacts with the substrate DNA
Torsional oscillations within a magnetic pore in the solar photosphere
Alfvén waves have proven to be important in a range of physical systems due to their ability to transport non-thermal energy over long distances in a magnetized plasma. This property is of specific interest in solar physics, where the extreme heating of the atmosphere of the Sun remains unexplained. In an inhomogeneous plasma such as a flux tube in the solar atmosphere, they manifest as incompressible torsional perturbations. However, despite evidence in the upper atmosphere, they have not been directly observed in the photosphere. Here, we report the detection of antiphase incompressible torsional oscillations observed in a magnetic pore in the photosphere by the Interferometric Bidimensional Spectropolarimeter. State-of-the-art numerical simulations suggest that a kink mode is a possible excitation mechanism of these waves. The excitation of torsional waves in photospheric magnetic structures can substantially contribute to the energy transport in the solar atmosphere and the acceleration of the solar wind, especially if such signatures will be ubiquitously detected in even smaller structures with the forthcoming next generation of solar telescopes
The protein-protein interactions required for assembly of the Tn3 resolution synapse
The siteâspecific recombinase Tn3 resolvase initiates DNA strand exchange when two res recombination sites and six resolvase dimers interact to form a synapse. The detailed architecture of this intricate recombination machine remains unclear. We have clarified which of the potential dimerâdimer interactions are required for synapsis and recombination, using a novel complementation strategy that exploits a previously uncharacterized resolvase from Bartonella bacilliformis (âBartâ). Tn3 and Bart resolvases recognize different DNA motifs, via diverged Câterminal domains (CTDs). They also differ substantially at Nâterminal domain (NTD) surfaces involved in dimerization and synapse assembly. We designed NTDâCTD hybrid proteins, and hybrid res sites containing both Tn3 and Bart dimer binding sites. Using these components in in vivo assays, we demonstrate that productive synapsis requires a specific âR â interface involving resolvase NTDs at all three dimerâbinding sites in res . Synapses containing mixtures of wildâtype Tn3 and Bart resolvase NTD dimers are recombinationâdefective, but activity can be restored by replacing patches of Tn3 resolvase R interface residues with Bart residues, or vice versa . We conclude that the Tn3 /Bart family synapse is assembled exclusively by R interactions between resolvase dimers, except for the one special dimerâdimer interaction required for catalysis
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