Expression divergence of the AGL6 MADS domain transcription factor lineage after a core eudicot duplication suggests functional diversification

Background: Because of their known role as transcriptional regulators of key plant developmental processes, the diversification of MADS-box gene function is thought to be a major driving force in the developmental evolution of plants. Yet the function of some MADS-box gene subfamilies has remained elusive thus far. One such lineage, AGL6, has now been functionally characterized in three angiosperm species, but a phylogenetic framework for comparison of AGL6 gene function is currently missing.status: publishe

Inferior outcome of addition of the aminopeptidase inhibitor tosedostat to standard intensive treatment for elderly patients with aml and high risk mds

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66–81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1–21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60–77%) vs 64% (55–73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation w

Transference of function shapes organ identity in the dove tree inflorescence

An important evolutionary mechanism shaping the biodiversity of flowering plants is the transfer of function from one plant organ to another. To investigate whether and how transference of function is associated with the remodeling of the floral organ identity program we studied Davidia involucrata, a species with conspicuous, petaloid bracts subtending a contracted inflorescence with reduced flowers. A detailed ontogeny enabled the interpretation of expression patterns of B-, C- and E-class homeotic MADS-box genes using qRT-PCR and in situ hybridization techniques. We investigated proteinprotein interactions using yeast two-hybrid assays. Although loss of organs does not appear to have affected organ identity in the retained organs of the reduced flowers of D. involucrata, the bracts express the B-class TM6 (Tomato MADS box gene 6) and GLOBOSA homologs, but not DEFICIENS, and the C-class AGAMOUS homolog, representing a subset of genes also involved in stamen identity. Our results may illustrate how petal identity can be partially transferred outside the flower by expressing a subset of stamen identity genes. This adds to the molecular mechanisms explaining the diversity of plant reproductive morphology

Analysis of developmental control genes using virus-induced gene silencing

A consistent challenge in studying the evolution of developmental processes has been the problem of explicitly assessing the function of developmental control genes in diverse species. In recent years, virus-induced gene silencing (VIGS) has proved to be remarkably adaptable and efficient in silencing developmental control genes in species across the angiosperms. Here we describe proven protocols for Nicotiana benthamiana and Papaver somniferum, representing a core and basal eudicot species.status: publishe

Pistillata-Duplications as a Mode for Floral Diversification in (Basal) Asterids

Basal asterid families, and to a lesser extent the asterids as a whole, are characterized by a high variation in petal and stamen morphology. Moreover, the Stamen number, the adnation of stamens to petals, and the degree of sympetaly vary considerably among basal asterid taxa. The B group genes, members of the APETALA3 (AP3) and PISTILLATA (PI) gene lineages, have been shown to specify petal and stamen identities in several core eudicot species. Duplicate genes in these lineages have been shown in some cases to have diversified in their function; for instance in Petunia, a PI paralog is required for the fusion of stamens to the corolla tube, illustrating that such genes belonging to this lineage are not just involved in specifying the identity of the stamens and petals but can also specify novel floral morphologies. This motivated us to study the duplication history of class B genes throughout asterid lineages, which comprise approximately one-third of all flowering plants. The evolutionary history of the PI gene subfamily indicates that the two genes in Petunia result from an ancient duplication event, coinciding with the origin of core asterids. A second duplication event occurred before the speciation of basal asterid Ericales families. These mid other duplications in the PI lineage are not correlated with duplications in the AP3 lineage. To understand the molecular evolution of the Ericales PI genes after duplication, we have described their expression patterns using reverse transcription polymerase chain reaction and in situ hybridization, reconstructed how selection shaped their protein sequences and tested their protein interaction specificity with other class B proteins. We find that after duplication, PI paralogs have acquired multiple different expression patterns and negative selective pressure on their codons is relaxed, whereas substitutions in sites putatively involved in protein-protein interactions show positive selection, allowing for a change in the interaction behavior of the PI paralogs after duplication. Together, these observations suggest that the asterids have preferentially recruited PI duplicate genes to diverse and potentially novel roles in asterid flower development.status: publishe

Gamma paleohexaploidy in the stem lineage of core eudicots: significance for MADS-box gene and species diversification

Comparative genome biology has unveiled the polyploid origin of all angiosperms and the role of recurrent polyploidization in the amplification of gene families and the structuring of genomes. Which species share certain ancient polyploidy events, and which do not, is ill defined because of the limited number of sequenced genomes and transcriptomes and their uneven phylogenetic distribution. Previously, it has been suggested that most, but probably not all, of the eudicots have shared an ancient hexaploidy event, referred to as the gamma triplication. In this study, detailed phylogenies of subfamilies of MADS-box genes suggest that the gamma triplication has occurred before the divergence of Gunnerales but after the divergence of Buxales and Trochodendrales. Large-scale phylogenetic and K-S-based approaches on the inflorescence transcriptomes of Gunnera manicata (Gunnerales) and Pachysandra terminalis (Buxales) provide further support for this placement, enabling us to position the gamma triplication in the stem lineage of the core eudicots. This triplication likely initiated the functional diversification of key regulators of reproductive development in the core eudicots, comprising 75% of flowering plants. Although it is possible that the gamma event triggered early core eudicot diversification, our dating estimates suggest that the event occurred early in the stem lineage, well before the rapid speciation of the earliest core eudicot lineages. The evolutionary significance of this paleopolyploidy event may thus rather lie in establishing a species lineage that was resilient to extinction, but with the genomic potential for later diversification. We consider that the traits generated from this potential characterize extant core eudicots both chemically and morphologically