Constituting approximately 10% of flowering plant species, orchids (Orchidaceae) display unique flower morphologies, possess an extraordinary diversity in lifestyle, and have successfully colonized almost every habitat on Earth 1-3 . Here we report the draft genome sequence of Apostasia shenzhenica 4 , a representative of one of two genera that form a sister lineage to the rest of the Orchidaceae, providing a reference for inferring the genome content and structure of the most recent common ancestor of all extant orchids and improving our understanding of their origins and evolution. In addition, we present transcriptome data for representatives of Vanilloideae, Cypripedioideae and Orchidoideae, and novel thirdgeneration genome data for two species of Epidendroideae, covering all five orchid subfamilies. A. shenzhenica shows clear evidence of a whole-genome duplication, which is shared by all orchids and occurred shortly before their divergence. Comparisons between A. shenzhenica and other orchids and angiosperms also permitted the reconstruction of an ancestral orchid gene toolkit. We identify new gene families, gene family expansions and contractions, and changes within MADS-box gene classes, which control a diverse suite of developmental processes, during orchid evolution. This study sheds new light on the genetic mechanisms underpinning key orchid innovations, including the development of the labellum and gynostemium, pollinia, and seeds without endosperm, as well as the evolution of epiphytism; reveals relationships between the Orchidaceae subfamilies; and helps clarify the evolutionary history of orchids within the angiosperms.

While it has long been known that inflammation and infection reduce expression of hepatic cytochrome P450 (CYP) genes involved in xenobiotic metabolism and that exposure to xenobiotic chemicals can impair immune function, the molecular mechanisms underlying both of these phenomena have remained largely unknown. Here we show that activation of the nuclear steroid and xenobiotic receptor (SXR) by commonly used drugs in humans inhibits the activity of NF-κB, a key regulator of inflammation and the immune response. NF-κB target genes are upregulated and small bowel inflammation is significantly increased in mice lacking the SXR ortholog pregnane X receptor (PXR), thereby demonstrating a direct link between SXR and drug-mediated antagonism of NF-κB. Interestingly, NF-κB activation reciprocally inhibits SXR and its target genes whereas inhibition of NF-κB enhances SXR activity. This SXR/PXR-NF-κB axis provides a molecular explanation for the suppression of hepatic CYP mRNAs by inflammatory stimuli as well as the immunosuppressant effects of xenobiotics and SXR-responsive drugs. This mechanistic relationship has clinical consequences for individuals undergoing therapeutic exposure to the wide variety of drugs that are also SXR agonists.

Publisher's copyright statement:Additional information: Use policyThe full-text may be used and/or reproduced, and given to third parties in any format or medium, without prior permission or charge, for personal research or study, educational, or not-for-pro t purposes provided that:• a full bibliographic reference is made to the original source • a link is made to the metadata record in DRO • the full-text is not changed in any way The full-text must not be sold in any format or medium without the formal permission of the copyright holders.Please consult the full DRO policy for further details. Dt, 0.56 × 10 -3 ) ( Fig. 1d and Supplementary Fig. 3). This shows that a large amount is associated with the development of the long fiber trait in cultivated cotton (Fig. 3b). 217Domestication has led to the transformation of cotton fiber from brown to white. 218To understand this phenomenon, we examined two homoeologous gene pairs only 219 subjected to domestication selection in the Dt, 4-COUMARATE:COA LIGASE (4CL) 220 and CHALCONE SYNTHASE (CHS), which encode enzymes involved in the 221 phenylpropanoid metabolic pathway ( Fig. 3c and Supplementary Fig. 6 Fig. 3c). These SNPs display reductions in nucleotide diversity that occurred 225 during domestication (Fig. 3c). Interestingly, we found that the two SNPs in the Fig. 8) 42 . We identified a total of 188,360 DNase I-hypersensitive 248 sites (DHSs) in cotton leaves and fibers, of which ca. 47% are common to both tissues 249 (Fig. 4a). DHSs were preferentially identified in chromosomal arms and 250 approximately half were detected in promoter and intergenic regions ( Fig. 4b and 251 Supplementary Fig. 9). We found DHSs are hypo-methylated, consistent with 252 previous studies 42 (Fig. 4c) H3K4me1 and inactive H3K9me2 (Fig. 4d). Intergenic DHSs were also found to 255 exhibit an enrichment of H3K4me3 and H3K27me3, but depletion of H3K9me2 and 256 no enrichment of H3K4me1 (Fig. 4e). As predicted, the patterns of chromatin 257 modification marks in cotton are different between genic and TE regions 258 ( Supplementary Fig. 10). In addition, genes with promoter DHSs are generally 259 expressed at a higher level in both tissues than those without promoter DHSs (Fig. 4f), 260 and tissue-specific promoter DHSs corresponded to higher levels of gene expression 261 ( Fig. 4g) Hi-C analysis was carried out using the TM-1 accession to characterize global 296 chromatin interactions. We generated 1.1 billion Hi-C paired-end reads, of which ca. possible Hi-C bias, HindIII fragments of less than 2 kb were merged to obtain 299 305,682 chromosomal anchor regions (Fig. 5a). On the basis of a high-quality 300 genome assembly of TM-1 (Supplementary Fig. 11), we used the Hi-C data to 301 characterize the cotton chromatin interactome (Supplementary Fig. 12) and ( Fig. 5b), but many topologically associated domain-like (TAD-like) regions were 305 identified (Fig. 5c, Supplementary Fig. 13 and Supplementary are less frequent at regions marked by H3K9me2 (Fig. 5d). (Fig. 5g). 320We...

Orchids make up about 10% of all seed plant species, have great economical value, and are of specific scientific interest because of their renowned flowers and ecological adaptations. Here, we report the first draft genome sequence of a lithophytic orchid, Dendrobium catenatum. We predict 28,910 protein-coding genes, and find evidence of a whole genome duplication shared with Phalaenopsis. We observed the expansion of many resistance-related genes, suggesting a powerful immune system responsible for adaptation to a wide range of ecological niches. We also discovered extensive duplication of genes involved in glucomannan synthase activities, likely related to the synthesis of medicinal polysaccharides. Expansion of MADS-box gene clades ANR1, StMADS11, and MIKC*, involved in the regulation of development and growth, suggests that these expansions are associated with the astonishing diversity of plant architecture in the genus Dendrobium. On the contrary, members of the type I MADS box gene family are missing, which might explain the loss of the endospermous seed. The findings reported here will be important for future studies into polysaccharide synthesis, adaptations to diverse environments and flower architecture of Orchidaceae.

Vitamin K 2 is a critical nutrient required for blood clotting that also plays an important role in bone formation. Vitamin K 2 supplementation up-regulates the expression of bone markers, increases bone density in vivo, and is used clinically in the management of osteoporosis. The mechanism of vitamin K 2 action in bone formation was thought to involve its normal role as an essential cofactor for ␥-carboxylation of bone matrix proteins. However, there is evidence that suggests vitamin K 2 also has a transcriptional regulatory function. Vitamin K 2 bound to and activated the orphan nuclear receptor SXR and induced expression of the SXR target gene, CYP3A4, identifying it as a bona fide SXR ligand. Vitamin K 2 treatment of osteosarcoma cells increased mRNA levels for the osteoblast markers bone alkaline phosphatase, osteoprotegerin, osteopontin, and matrix Gla protein. The known SXR activators rifampicin and hyperforin induced this panel of bone markers to an extent similar to vitamin K 2 . Vitamin K 2 was able to induce bone markers in primary osteocytes isolated from wild-type murine calvaria but not in cells isolated from mice deficient in the SXR ortholog PXR. We infer that vitamin K 2 is a transcriptional regulator of bonespecific genes that acts through SXR to favor the expression of osteoblastic markers. Thus, SXR has a novel role as a mediator of bone homeostasis in addition to its role as a xenobiotic sensor. An important implication of this work is that a subset of SXR activators may function as effective therapeutic agents for the management of osteoporosis.