Biology subjects

Sharpe, A.

Publications and source records attributed to Sharpe, A..

6 recordsLinked to original sources

bioRxiv2023

Mapping QTL for vernalization requirement identified adaptive divergence of the candidate gene Flowering Locus C in polyploid Camelina sativa

Vernalization requirement is an integral component of flowering in winter-type plants. The availability of winter ecotypes among Camelina species facilitated the mapping of QTL for vernalization requirement in C. sativa. An inter- and intraspecific crossing scheme between related Camelina species, where two different sources of the winter-type habit were used, resulted in the development of two segregating populations. Linkage maps generated with sequence-based markers identified three QTL associated with vernalization requirement in C. sativa; two from the inter-specific (chromosomes 13 and 20) and one from the intra-specific cross (chromosome 8). Notably, the three loci were mapped to different homologous regions of the hexaploid C. sativa genome. All three QTL were found in proximity to FLOWERING LOCUS C (FLC), variants of which have been reported to affect the vernalization requirement in plants. Temporal transcriptome analysis for winter-type Camelina alyssum demonstrated reduction in expression of FLC on chromosomes 13 and 20 during cold treatment, which would trigger flowering, since FLC would be expected to suppress floral initiation. FLC on chromosome 8 also showed reduced expression in the C. sativa ssp. pilosa winter parent upon cold treatment, but was expressed at very high levels across all time points in the spring-type C. sativa. The chromosome 8 copy carried a deletion in the spring-type line, which could impact its functionality. Contrary to previous reports, all three FLC loci can contribute to controlling the vernalization response in C. sativa and provide opportunities for manipulating this requirement in the crop. Significance StatementDeveloping winter C. sativa germplasm is an important breeding goal for this alternative oilseed, with application in the food, fuel and bioproduct industries. Studying the genetic architecture of the vernalization response has shown that contrary to previous reports all three FLC loci in Camelina species could be exploited to manipulate this important trait.

plant biology↗

bioRxiv2021

Microenvironmental correlates of immune checkpoint inhibitor response in human melanoma brain metastases revealed by T cell receptor and single-cell RNA sequencing

Melanoma-derived brain metastases (MBM) represent an unmet clinical need due to central nervous system (CNS) progression as a frequent, end-stage site of disease. Immune checkpoint inhibition (ICI) represents a clinical opportunity against MBM; however, the MBM tumor microenvironment (TME) has not been fully elucidated in the context of ICI. To dissect unique MBM-TME elements and correlates of MBM-ICI response, we collected 32 fresh MBM and performed single cell RNA sequencing of the MBM-TME and T cell receptor clonotyping on T cells from MBM and matched blood and extracranial lesions. We observed myeloid phenotypic heterogeneity, most notably multiple distinct neutrophil states including an IL-8 expressing population that correlated with malignant cell epithelial-to-mesenchymal transition. Additionally, we observe significant relationships between intracranial T cell phenotypes and the distribution of T cell clonotypes intracranially and peripherally. We found that the phenotype, clonotype, and overall number of MBM-infiltrating T cells were associated with response to ICI, suggesting that ICI-responsive MBMs interact with peripheral blood in a manner similar to extracranial lesions. These data demonstrate unique features of the MBM-TME, which may represent potential targets to improve clinical outcomes for patients with MBM.

cancer biology↗

bioRxiv2021

Deep Neural Networks for Genomic Prediction Do Not Estimate Marker Effects

Genomic prediction is a promising technology for advancing both plant and animal breeding, with many different prediction models evaluated in the literature. It has been suggested that the ability of powerful nonlinear models such as deep neural networks to capture complex epistatic effects between markers offers advantages for genomic prediction. However, these methods tend not to outperform classical linear methods, leaving it an open question why this capacity to model nonlinear effects does not seem to result in better predictive capability. In this work, we propose the theory that, due to a principle called shortcut learning, deep neural networks tend to base their predictions on overall genetic relatedness, rather than on the effects of particular markers, such as epistatic effects. Using several datasets of crop plants (lentil, wheat, and Brassica carinata), we demonstrate the networks indifference to the values of the markers by showing that the same network, provided with only the locations of matches between markers for two individuals, is able to perform prediction to the same level of accuracy.

bioinformatics↗

bioRxiv2020

Maternal genome dominance in early plant embryogenesis

Previous studies have alternately supported and discounted the hypothesis that the maternal genome plays a predominant role in early embryogenesis in plants. We used 24 embryo defective (emb) mutants of Arabidopsis thaliana to test for maternal and paternal effects in early embryogenesis. 5 emb mutants had equal maternal and paternal effects, 5 showed maternal effects and weak paternal effects, and the remaining 14 emb mutants conditioned only maternal effects, demonstrating a more important role for the maternal allele for most of these EMB genes. To assess genome-wide maternal and paternal contributions to early embryos, we produced allele-specific transcriptomes from zygote to mature stage embryos derived from reciprocal crosses of Columbia-0 and Tsu-1, a hybrid combination we show to be a faithful proxy for isogenic Columbia-0. Parent-of-origin analysis of these transcriptomes revealed a reciprocal maternal bias in thousands of genes from the zygote to octant stage. This bias greatly diminished by the globular stage, and was absent at later stages. Comparison with egg cell transcriptomes revealed no correlation between transcript levels in the egg and maternal bias in pre-globular embryos, suggesting that the maternal bias observed in early embryos is due to preferential zygotic transcription of maternal alleles. Taken together, the functional and transcriptome data presented here support a predominant role for the maternal genome in early Arabidopsis embryogenesis. SignificanceIn both animals and plants, the zygote is produced by the union of the egg and sperm cells. In animals, it is well accepted that mRNAs and proteins from the egg direct the first steps of embryogenesis. Here we present genetic and genomic experiments that support a predominant role for the maternal genome in early embryogenesis of plants, as well. In contrast to animals, our data suggest that this maternal influence is primarily derived not from inheritance of egg transcripts, but from preferential transcription of maternal alleles in the zygote and early embryo. This transient maternal zygotic bias may reflect an ancestral condition to diminish paternal influence on early embryogenesis in outcrossing plants.

plant biology↗

bioRxiv2019

Chromosome-scale genome assembly provides insights into rye biology, evolution, and agronomic potential

We present a chromosome-scale annotated assembly of the rye (Secale cereale L. inbred line Lo7) genome, which we use to explore Triticeae genomic evolution, and ryes superior disease and stress tolerance. The rye genome shares chromosome-level organization with other Triticeae cereals, but exhibits unique retrotransposon dynamics and structural features. Crop improvement in rye, as well as in wheat and triticale, will profit from investigations of rye gene families implicated in pathogen resistance, low temperature tolerance, and fertility control systems for hybrid breeding. We show that rye introgressions in wheat breeding panels can be characterised in high-throughput to predict the yield effects and trade-offs of rye chromatin.

genomics↗

bioRxiv2018

Optical and physical mapping with local finishing enables megabase-scale resolution of agronomically important regions in the wheat genome

BackgroundNumerous scaffold-level sequences for wheat are now being released and, in this context, we report on a strategy for improving the overall assembly to a level comparable to that of the human genome.\n\nResultsUsing chromosome 7A of wheat as a model, sequence-finished megabase scale sections of this chromosome were established by combining a new independent assembly based on a BAC-based physical map, BAC pool paired end sequencing, chromosome arm specific mate-pair sequencing and Bionano optical mapping with the IWGSC RefSeq v1.0 sequence and its underlying raw data. The combined assembly results in 18 super-scaffolds across the chromosome. The value of finished genome regions is demonstrated for two approximately 2.5 Mb regions associated with yield and the grain quality phenotype of fructan carbohydrate grain levels. In addition, the 50 Mb centromere region analysis incorporates cytological data highlighting the importance of non-sequence data in the assembly of this complex genome region.\n\nConclusionsSufficient genome sequence information is shown to be now available for the wheat community to produce sequence-finished releases of each chromosome of the reference genome. The high-level completion identified that an array of seven fructosyl transferase genes underpins grain quality and yield attributes are affected by five f-box-only-protein-ubiquitin ligase domain and four root-specific lipid transfer domain genes. The completed sequence also includes the centromere.

genomics↗