The SUMO ligase MMS21 profoundly influences maize development through its impact on genome activity and stability

The post-translational addition of SUMO plays essential roles in numerous eukaryotic processes including cell division, transcription, chromatin organization, DNA repair, and stress defense through its selective conjugation to numerous targets. One prominent plant SUMO ligase is METHYL METHANESULFONATE-SENSITIVE (MMS)-21/HIGH-PLOIDY (HPY)-2/NON-SMC-ELEMENT (NSE)-2, which has been connected genetically to development and endoreduplication. Here, we describe the potential functions of MMS21 through a collection of UniformMu and CRISPR/Cas9 mutants in maize (Zea mays) that display either seed lethality or substantially compromised pollen germination and seed/vegetative development. RNA-seq analyses of leaves, embryos, and endosperm from mms21 plants revealed a substantial dysregulation of the maize transcriptome, including the ectopic expression of seed storage protein mRNAs in leaves and altered accumulation of mRNAs associated with DNA repair and chromatin dynamics. Interaction studies demonstrated that MMS21 associates in the nucleus with the NSE4 and STRUCTURAL MAINTENANCE OF CHROMOSOMES (SMC)-5 components of the chromatin organizer SMC5/6 complex, with in vitro assays confirming that MMS21 will SUMOylate SMC5. Comet assays measuring genome integrity, sensitivity to DNA-damaging agents, and protein versus mRNA abundance comparisons implicated MMS21 in chromatin stability and transcriptional controls on proteome balance. Taken together, we propose that MMS21-directed SUMOylation of the SMC5/6 complex and other targets enables proper gene expression by influencing chromatin structure.

The Overlooked Hybrid: Geographic Distribution and Niche Differentiation Between Spartina Cytotypes (Poaceae) in Wadden Sea Salt Marshes

Whole genome duplications (WGDs) lead to polyploid specimens and are regarded as major drivers for speciation and diversification in plants. One prevalent problem when studying WGDs is that effects of polyploidization in ancient polyploids cannot be disentangled from the consequences of selective evolutionary forces. Cytotypic differences in distribution, phenotypic appearance and in response to surface elevation (determined by HOF-modeling) were identified in a relatively young taxa-group of a hexaploid F1-hybrid (Spartina× townsendii H. Groves & J. Groves, Poaceae) and its dodecaploid descendent (Spartina anglica C.E. Hubbard, Poaceae) using vegetation assessments (1029 plots; 1 × 1 m2) from the European Wadden Sea mainland salt marshes, including elevational and mean high tidal (MHT) data. While the F1-hybrid was mainly present in the eastern part of the Wadden Sea, its dodecaploid descendent occurred in the entire Wadden Sea area. The Spartina cytotypes differed in phenotypes (median of Spartina cover: hexaploid = 25% vs. dodecaploid = 12%) and in elevational niche-optimum (hexaploid = − 49.5 cm MHT vs. dodecaploid = 8.0 cm MHT). High ploidy levels correlated with establishment success in Spartina along geographic gradients but did not seem to increase the capacity to cope with abiotic severity downwards the elevational gradient in salt marshes.

Pioneering polyploids: the impact of whole-genome duplication on biome shifting in New Zealand Coprosma (Rubiaceae) and Veronica (Plantaginaceae)

The role of whole-genome duplication (WGD) in facilitating shifts into novel biomes remains unknown. Focusing on two diverse woody plant groups in New Zealand, Coprosma (Rubiaceae) and Veronica (Plantaginaceae), we investigate how biome occupancy varies with ploidy level, and test the hypothesis that WGD increases the rate of biome shifting. Ploidy levels and biome occupancy (forest, open and alpine) were determined for indigenous species in both clades. The distribution of low-ploidy ( Coprosma : 2 x , Veronica : 6 x ) versus high-ploidy ( Coprosma : 4–10 x , Veronica : 12–18 x ) species across biomes was tested statistically. Estimation of the phylogenetic history of biome occupancy and WGD was performed using time-calibrated phylogenies and the R package BioGeoBEARS. Trait-dependent dispersal models were implemented to determine support for an increased rate of biome shifting among high-ploidy lineages. We find support for a greater than random portion of high-ploidy species occupying multiple biomes. We also find strong support for high-ploidy lineages showing a three- to eightfold increase in the rate of biome shifts. These results suggest that WGD promotes ecological expansion into new biomes.

M2 macrophages, but not M1 macrophages, support megakaryopoiesis by upregulating PI3K-AKT pathway activity

Dysfunctional megakaryopoiesis hampers platelet production, which is closely associated with thrombocytopenia (PT). Macrophages (MФs) are crucial cellular components in the bone marrow (BM) microenvironment. However, the specific effects of M1 MФs or M2 MФs on regulating megakaryocytes (MKs) are largely unknown. In the current study, aberrant BM-M1/M2 MФ polarization, characterized by increased M1 MФs and decreased M2 MФs and accompanied by impaired megakaryopoiesis-supporting abilities, was found in patients with PT post-allotransplant. RNA-seq and western blot analysis showed that the PI3K-AKT pathway was downregulated in the BM MФs of PT patients. Moreover, in vitro treatment with PI3K-AKT activators restored the impaired megakaryopoiesis-supporting ability of MФs from PT patients. Furthermore, we found M1 MФs suppress, whereas M2 MФs support MK maturation and platelet formation in humans. Chemical inhibition of PI3K-AKT pathway reduced megakaryopoiesis-supporting ability of M2 MФs, as indicated by decreased MK count, colony-forming unit number, high-ploidy distribution, and platelet count. Importantly, genetic knockdown of the PI3K-AKT pathway impaired the megakaryopoiesis-supporting ability of MФs both in vitro and in a MФ-specific PI3K-knockdown murine model, indicating a critical role of PI3K-AKT pathway in regulating the megakaryopoiesis-supporting ability of M2 MФs. Furthermore, our preliminary data indicated that TGF-β released by M2 MФs may facilitate megakaryopoiesis through upregulation of the JAK2/STAT5 and MAPK/ERK pathways in MKs. Taken together, our data reveal that M1 and M2 MФs have opposing effects on MKs in a PI3K-AKT pathway-dependent manner, which may lead to new insights into the pathogenesis of thrombocytopenia and provide a potential therapeutic strategy to promote megakaryopoiesis.

High KIFC1 expression is associated with poor prognosis in prostate cancer

Kinesins play important roles in the progression and development of cancer. Kinesin family member C1 (KIFC1), a minus end-directed motor protein, is a novel Kinesin involved in the clustering of excess centrosomes found in cancer cells. Recently KIFC1 has shown to play a role in the progression of many different cancers, however, the involvement of KIFC1 in the progression of prostate cancer (PCa) is still not well understood. This study investigated the expression and clinical significance of KIFC1 in PCa by utilizing multiple publicly available datasets to analyze KIFC1 expression in patient samples. High KIFC1 expression was found to be associated with high Gleason score, high tumor stage, metastatic lesions, high ploidy levels, and lower recurrence-free survival. These results reveal that high KIFC1 levels are associated with a poor prognosis for PCa patients and could act as a prognostic indicator for PCa patients as well.

Comparative analysis of early divergent land plants and construction of DNA tools for hyper-expression in Marchantia chloroplasts

ABSTRACTChloroplast genes are present at high ploidy in plants, and capable of driving very high levels of gene expression if mRNA production and stability are properly regulated. Marchantia polymorpha is a simple model plant that allows rapid transformation studies, however post-transcriptional regulation in plastids is poorly characterized in this liverwort. We have mapped patterns of transcription in Marchantia chloroplasts. Furthermore, we have obtained and compared sequences from 51 early-divergent plant species, and identified putative sites for pentatricopeptide repeat protein binding that are thought to play important roles in mRNA stabilisation. Candidate binding sites were tested for their ability to confer high levels of reporter gene expression in Marchantia chloroplasts, and levels of protein production and effects on growth were measured in homoplasmic transformed plants. We have produced novel DNA tools for protein hyper-expression in a facile plant system that is a test-bed for chloroplast engineering.

A perfect storm: ploidy and preadaptation facilitate Saccharum spontaneum escape and invasion in the Republic of Panama

Polyploidy may contribute to invasive ability as it can lead to high survival and fitness during establishment and enhance the processes of adaptation to novel environments by increasing genetic diversity in invading propagules. Many grasses are polyploid and many are aggressive invaders, making them persistent problems in disturbed environments worldwide. Today, vast areas of central Panama are dominated by Saccharum spontaneum, a perennial grass that originates from Asia. While widely regarded as invasive, it is not known when or how it arrived in Panama. We explore hypotheses regarding the timing and origins of this invasion through literature review and comparisons of genetic diversity in Panama with accessions from available sugarcane germplasm collections, highlighting historical accessions that were likely brought to Panama in 1939 as part of a USDA sugarcane germplasm collection. Samples were haplotyped at two chloroplast loci and genotyped using eight microsatellite markers. All sequenced individuals from Panama belong to a single chloroplast lineage which is common worldwide and was common in the Historic germplasm collection. Although genotypic diversity was extremely high in all samples due to high ploidy, samples from Panama had reduced diversity and clustered with several accessions in the Historic collection which had the same haplotype and high ploidy levels. Our results suggest that accidental escape from the historical sugarcane germplasm collection is the likely origin of the S. spontaneum invasion in Panama. Intraspecific hybridization among several historical accessions and pre-adaptation to local conditions may have facilitated its rapid spread and persistence. We discuss the implications of our findings for biosecurity of germplasm collections.

Thermodynamic energetics underlying genomic instability and whole-genome doubling in cancer

Genomic instability contributes to tumorigenesis through the amplification and deletion of cancer driver genes. DNA copy number (CN) profiling of ensembles of tumors allows a thermodynamic analysis of the profile for each tumor. The free energy of the distribution of CNs is found to be a monotonically increasing function of the average chromosomal ploidy. The dependence is universal across several cancer types. Surprisal analysis distinguishes two main known subgroups: tumors with cells that have or have not undergone whole-genome duplication (WGD). The analysis uncovers that CN states having a narrower distribution are energetically more favorable toward the WGD transition. Surprisal analysis also determines the deviations from a fully stable-state distribution. These deviations reflect constraints imposed by tumor fitness selection pressures. The results point to CN changes that are more common in high-ploidy tumors and thus support altered selection pressures upon WGD.