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Biology subjects

Brown, P. J.

Publications and source records attributed to Brown, P. J..

39 records · Page 3Linked to original sources

Leveraging mutational burden for complex trait prediction in sorghum

Sorghum (Sorghum bicolor (L.) Moench) is a major staple food cereal for millions of people worldwide. The sorghum genome, like other species, accumulates deleterious mutations, likely impacting its fitness. Though selection keeps deleterious mutations rare, their complete removal from the genome is impeded due to lack of recombination, drift, and their coupling with favorable loci. To study how deleterious mutations impact agronomic phenotypes, we identified putative deleterious mutations among ~5.5M segregating variants of 229 diverse sorghum lines. We provide the whole-genome estimate of the deleterious burden in sorghum, showing that about 33% of nonsynonymous substitutions are putatively deleterious. The pattern of mutation burden varies appreciably among racial groups; the caudatum shows higher mutation burden while the guinea has lower burden. Across racial groups, the mutation burden correlated negatively with biomass, plant height, Specific Leaf Area (SLA), and tissue starch content, suggesting deleterious burden decreases trait fitness. Putatively deleterious variants explain roughly half of the genetic variance. However, there is only moderate improvement in total heritable variance explained for biomass (7.6%) and plant height (5.2%). There is no advantage in total heritable variance for SLA and starch. The contribution of putatively deleterious variants to phenotypic diversity therefore appears to be dependent on the genetic architecture of traits. Overall, our results suggest that including putatively deleterious variants in models do not significantly improve breeding accuracy because of extensive linkage. However, knowledge of deleterious variants could be leveraged for sorghum breeding through genome editing.

genetics↗

A Chemical Biology Toolbox for the Study of Protein Methyltransferases and Epigenetic Signaling

Protein methyltransferases (PMTs) comprise a major class of epigenetic regulatory enzymes with therapeutic relevance. Here we present a collection of chemical probes and associated reagents and data to elucidate the function of human and murine PMTs in cellular studies. Our collection provides inhibitors and antagonists that together modulate most of the key regulatory methylation marks on histones H3 and H4, providing an important resource for modulating cellular epigenomes. We describe a comprehensive and comparative characterization of the probe collection with respect to their potency, selectivity, and mode of inhibition. We demonstrate the utility of this collection in CD4+ T cell differentiation assays revealing the remarkable potential of individual probes to alter multiple T cell subpopulations with important implications for T cell-mediated processes such as inflammation and immuno-oncology. In particular, we demonstrate a role for DOT1L in limiting Th1 cell differentiation and maintaining lineage integrity.

biochemistry↗

Elevated ozone reduces photosynthetic carbon gain by accelerating leaf senescence of inbred and hybrid maize in a genotype-specific manner

Exposure to elevated tropospheric ozone concentration ([O3]) accelerates leaf senescence in many C3 crops. However, the effects of elevated [O3] on C4 crops including maize (Zea mays L.) are poorly understood in terms of physiological mechanism and genetic variation in sensitivity. Using Free Air gas Concentration Enrichment (FACE), we investigated the photosynthetic response of 18 diverse maize inbred and hybrid lines to season-long exposure to elevated [O3] (~100 nL L-1) in the field. Gas exchange was measured on the leaf subtending the ear throughout the grain filling period. On average over the lifetime of the leaf, elevated [O3] led to reductions in photosynthetic CO2 assimilation of both inbred (-22%) and hybrid (-33%) genotypes. There was significant variation among both inbred and hybrid lines in the sensitivity of photosynthesis to elevated [O3], with some lines showing no change in photosynthesis at elevated [O3]. Based on analysis of inbred line B73, the reduced CO2 assimilation at elevated [O3] was associated with accelerated senescence decreasing photosynthetic capacity, and not altered stomatal limitation. These findings across diverse maize genotypes could advance the development of more ozone tolerant maize, and provide experimental data for parameterization and validation of studies modeling how O3 impacts crop performance.

plant biology↗