Allotetraploid cotton species (Gossypium hirsutum and Gossypium barbadense) have long been cultivated worldwide for natural renewable textile fibers. The draft genome sequences of both species are available but they are highly fragmented and incomplete 1-4. Here we report referencegrade genome assemblies and annotations for G. hirsutum accession Texas Marker-1 (TM-1) and G. barbadense accession 3-79 by integrating single-molecule real-time sequencing, BioNano optical mapping and high-throughput chromosome conformation capture techniques. Compared with previous assembled draft genomes 1,3 , these genome sequences show considerable improvements in contiguity and completeness for regions with high content of repeats such as centromeres. Comparative genomics analyses identify extensive structural variations that probably occurred after polyploidization, highlighted by large paracentric/pericentric inversions in 14 chromosomes. We constructed an introgression line population to introduce favorable chromosome segments from G. barbadense to G. hirsutum, allowing us to identify 13 quantitative trait loci associated with superior fiber quality. These resources will accelerate evolutionary and functional genomic studies in cotton and inform future breeding programs for fiber improvement. Cotton represents the largest source of natural textile fibers in the world. Over 90% of annual fiber production comes from allotetraploid cotton (G. hirsutum and G. barbadense), which originated from an allopolyplodization event approximately 1-2 million year ago, followed by millennia of asymmetric subgenome selection 5,6. G. hirsutum is cultivated all over the world because of its high yield and G. barbadense is prized for its superior fiber quality. To cultivate G. hirsutum that produces longer, finer and stronger fibers, one approach is to introduce the superior fiber traits from G. barbadense into G. hirsutum. A genomics-enabled breeding strategy requires a detailed and robust understanding of genomic organization. Genomic feature G. hirsutum G. barbadense

Gossypium hirsutum contributes the most production of cotton fibre, but G. barbadense is valued for its better comprehensive resistance and superior fibre properties. However, the allotetraploid genome of G. barbadense has not been comprehensively analysed. Here we present a high-quality assembly of the 2.57 gigabase genome of G. barbadense, including 80,876 protein-coding genes. The double-sized genome of the A (or At) (1.50 Gb) against D (or Dt) (853 Mb) primarily resulted from the expansion of Gypsy elements, including Peabody and Retrosat2 subclades in the Del clade, and the Athila subclade in the Athila/Tat clade. Substantial gene expansion and contraction were observed and rich homoeologous gene pairs with biased expression patterns were identified, suggesting abundant gene sub-functionalization occurred by allopolyploidization. More specifically, the CesA gene family has adapted differentially temporal expression patterns, suggesting an integrated regulatory mechanism of CesA genes from At and Dt subgenomes for the primary and secondary cellulose biosynthesis of cotton fibre in a “relay race”-like fashion. We anticipate that the G. barbadense genome sequence will advance our understanding the mechanism of genome polyploidization and underpin genome-wide comparison research in this genus.

Based on 1075 and 1059 QTL from intraspecific Upland and interspecific Upland × Pima populations, respectively, the identification of QTL clusters and hotspots provides a useful resource for cotton breeding. Mapping of quantitative trait loci (QTL) is a pre-requisite of marker-assisted selection for crop yield and quality. Recent meta-analysis of QTL in tetraploid cotton (Gossypium spp.) has identified regions of the genome with high concentrations of QTL for various traits called clusters and specific trait QTL called hotspots or meta-QTL (mQTL). However, the meta-analysis included all population types of Gossypium mixing both intraspecific G. hirsutum and interspecific G. hirsutum × G. barbadense populations. This study used 1,075 QTL from 58 publications on intraspecific G. hirsutum and 1,059 QTL from 30 publications on G. hirsutum × G. barbadense populations to perform a comprehensive comparative analysis of QTL clusters and hotspots between the two populations for yield, fiber and seed quality, and biotic and abiotic stress tolerance. QTL hotspots were further analyzed for mQTL within the hotspots using Biomercator V3 software. The ratio of QTL between the two population types was proportional yet differences in hotspot type and placement were observed between the two population types. However, on some chromosomes QTL clusters and hotspots were similar between the two populations. This shows that there are some universal QTL regions in the cultivated tetraploid cotton which remain consistent and some regions which differ between population types. This study for the first time elucidates the similarities and differences in QTL clusters and hotspots between intraspecific and interspecific populations, providing an important resource to cotton breeding programs in marker-assisted selection .

BackgroundNAD (P) H: quinone oxidoreductase 1 (NQO1) is a xenobiotic metabolizing enzyme that detoxifies chemical stressors and antioxidants, providing cytoprotection in normal tissues. However, high-level expression of NQO1 has been correlated with numerous human malignancies, suggesting a role in carcinogenesis and tumor progression. This study aimed to explore the clinicopathological significance of NQO1 and as a prognostic determinant in breast cancer.MethodsA total of 176 breast cancer patients with strict follow-up, 45 ductal carcinoma in situ (DCIS), 22 hyperplasia and 52 adjacent non-tumor breast tissues were selected for immunohistochemical staining of NQO1 protein. Immunofluorescence staining was also performed to detect the subcellular localization of NQO1 protein in MCF-7 breast cancer cells. Eight fresh breast cancers paired with adjacent non-tumor tissues were quantified using real time RT-PCR (qRT-PCR) and western blot. The correlations between NQO1 overexpression and the clinical features of breast cancer were evaluated using chi-square test and Fisher’s exact tests. The survival rate was calculated using the Kaplan–Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazards models.ResultsNQO1 protein showed a mainly cytoplasmic staining pattern in breast cancer. The strongly positive rate of NQO1 protein was 61.9% (109/176) in breast cancer, and was significantly higher than in DCIS (31.1%, 14/45), hyperplasia tissues (13.6%, 3/22) and adjacent non-tumor tissues (13.5%, 7/52). High-level expression of NQO1 protein was correlated with late clinical stage, poor differentiation, lymph node metastasis, Her2 expression and disease-free and 10-year overall survival rates in breast cancer. Moreover, multivariate analysis suggested that NQO1 emerged as a significant independent prognostic factor along with clinical stage and Her2 expression status in patients with breast cancer.ConclusionsHigh-level expression of NQO1 appears to be associated with breast cancer progression, and may be a potential biomarker for poor prognostic evaluation of breast cancers.

Purpose: Elevated metabolic activity of ovarian cancer cells causes increased ubiquitinproteasome-system (UPS) stress, resulting in their greater sensitivity to the toxic effects of proteasomal inhibition. The proteasomes and a potentially compensatory histone deacetylase 6 (HDAC6)-dependent lysosomal pathway mediate eukaryotic protein turnover. We hypothesized that up-regulation of the HDAC6-dependent lysosomal pathway occurs in response to UPS stress and proteasomal inhibition, and thus, ovarian cancer cell death can be triggered most effectively by coinhibition of both the proteasome-and HDAC6-dependent protein degradation pathways. Experimental Design: To address this hypothesis, we examined HDAC6 expression patterns in normal and cancerous ovarian tissues and used a novel HDAC6-specific inhibitor, NK84, to address HDAC6 function in ovarian cancer. Results: Abnormally high levels of HDAC6 are expressed by ovarian cancer cells in situ and in culture relative to benign epithelium and immortalized ovarian surface epithelium, respectively. Specific HDAC6 inhibition acts in synergy with the proteasome inhibitor Bortezomib (PS-341) to cause selective apoptotic cell death of ovarian cancer cells at doses that do not cause significant toxicity when used individually. Levels of UPS stress regulate the sensitivity of ovarian cancer cells to proteasome/HDAC6 inhibition. Pharmacologic inhibition of HDAC6 also reduces ovarian cancer cell spreading and migration consistent with its known function in regulating microtubule polymerization via deacetylation of a-tubulin. Conclusion: Our results suggest the elevation of both the proteasomal and alternate HDAC6-dependent proteolytic pathways in ovarian cancer and the potential of combined inhibition of proteasome and HDAC6 as a therapy for ovarian cancer.