A merger between compatible but divergent genomes supports allopolyploidization in the Brassicaceae family

Hybridization and polyploidization are pivotal to plant evolution. Genetic crosses between distantly related species rarely occur in nature mainly due to reproductive barriers but how such hurdles can be overcome is largely unknown. xBrassicoraphanus is a fertile intergeneric allopolyploid synthesized between Brassica rapa and Raphanus sativus in the Brassicaceae family. Genomes of B. rapa and R. sativus are diverged enough to suppress synapsis formation between non-homologous progenitor chromosomes during meiosis, and we found that both genomes reside in the single nucleus of xBrassicoraphanus without genome loss or rearrangement. Expressions of syntenic orthologs identified in B. rapa and R. sativus were adjusted to a hybrid nuclear environment of xBrassicoraphanus, which necessitates reconfiguration of transcription network by rewiring cis-trans interactions. B. rapa coding sequences have a higher level of gene-body methylation than R. sativus, and such methylation asymmetry is maintained in xBrassicoraphanus. B. rapa-originated transposable elements were transcriptionally silenced in xBrassicoraphanus, rendered by gain of CHG methylation in trans via small RNAs derived from the same sequences of R. sativus subgenome. Our work proposes that not only transcription compatibility but also a certain extent of genome divergence supports hybrid genome stabilization, which may explain great diversification and expansion of angiosperms during evolution.

Identification of a novel Candida metapsilosis isolate suggests ongoing hybridization.

Candida metapsilosis is a member of the C. parapsilosis species complex, a group of opportunistic human pathogens. Of all the members of this complex, C. metapsilosis is the least virulent, and accounts for a small proportion of invasive Candida infections. Previous studies established that all C. metapsilosis isolates are hybrids, originating from a single hybridization event between two lineages, parent A and parent B. Here, we use MinION and Illumina sequencing to characterize a C. metapsilosis isolate that originated from a separate hybridization. One of the parents of the new isolate is very closely related to parent A. However, the other parent (parent C) is not the same as parent B. Unlike C. metapsilosis AB isolates, the C. metapsilosis AC isolate has not undergone introgression at the Mating Type-like Locus. In addition, the A and C haplotypes are not fully collinear. The C. metapsilosis AC isolate has undergone Loss of Heterozygosity (LOH) with a preference for haplotype A, indicating that this isolate is in the early stages of genome stabilization.

Untangling structural factors and evolutionary drivers in nascent polyploids

(1)Allopolyploids have globally higher fitness than their diploid progenitors however, by comparison, most resynthesized allopolyploids have poor fertility and highly unstable genome. Elucidating the evolutionary processes promoting genome stabilization and fertility is thus essential to comprehend allopolyploid success. (2)Using the Brassica model, we mimicked the speciation process of a nascent allopolyploid species by resynthesizing allotetraploid B. napus and systematically selecting for euploid individuals over eight generations in four independent allopolyploidization events with contrasted genetic backgrounds, cytoplasmic donors and polyploid formation type. We evaluated the evolution of meiotic behavior, fertility and identified rearrangements in S1 to S9 lineages, to explore the positive consequences of euploid selection on B. napus genome stability. (3)Recurrent selection of euploid plants for eight generations drastically reduced the percentage of aneuploid progenies as early as the fourth generation, concomitantly with a quasi disappearance of newly fixed homoeologous rearrangements. The consequences of homoeologous rearrangements on meiotic behavior and seed number strongly depended on the genetic background and cytoplasm donor. (4)The combined use of both self-fertilisation and outcrossing as well as recurrent euploid selection, allowed identification of genomic regions associated with fertility and meiotic behavior, providing complementary evidence to explain B. napus speciation success.

p53 deficiency triggers dysregulation of diverse cellular processes in physiological oxygen

The mechanisms by which TP53, the most frequently mutated gene in human cancer, suppresses tumorigenesis remain unclear. p53 modulates various cellular processes, such as apoptosis and proliferation, which has led to distinct cellular mechanisms being proposed for p53-mediated tumor suppression in different contexts. Here, we asked whether during tumor suppression p53 might instead regulate a wide range of cellular processes. Analysis of mouse and human oncogene-expressing wild-type and p53-deficient cells in physiological oxygen conditions revealed that p53 loss concurrently impacts numerous distinct cellular processes, including apoptosis, genome stabilization, DNA repair, metabolism, migration, and invasion. Notably, some phenotypes were uncovered only in physiological oxygen. Transcriptomic analysis in this setting highlighted underappreciated functions modulated by p53, including actin dynamics. Collectively, these results suggest that p53 simultaneously governs diverse cellular processes during transformation suppression, an aspect of p53 function that would provide a clear rationale for its frequent inactivation in human cancer.

Location specific annealing of miR-122 and other small RNAs defines an Hepatitis C Virus 5′ UTR regulatory element with distinct impacts on virus translation and genome stability

Hepatitis C virus (HCV) replication requires annealing of a liver specific small-RNA, miR-122 to 2 sites on 5′ untranslated region (UTR). Annealing has been reported to (a) stabilize the genome, (b) stimulate translation and (c) promote the formation of translationally active Internal Ribosome Entry Site (IRES) RNA structure. In this report, we map the RNA element to which small RNA annealing promotes HCV to nucleotides 1–44 and identify the relative impact of small RNA annealing on virus translation promotion and genome stabilization. We mapped the optimal region on the HCV genome to which small RNA annealing promotes virus replication to nucleotides 19–37 and found the efficiency of viral RNA accumulation decreased as annealing moved away from this region. Then, by using a panel of small RNAs that promote replication with varying efficiencies we link the efficiency of lifecycle promotion with translation stimulation. By contrast small RNA annealing stabilized the viral genome even if they did not promote virus replication. Thus, we propose that miR-122 annealing promotes HCV replication by annealing to an RNA element that activates the HCV IRES and stimulates translation, and that miR-122 induced HCV genome stabilization is insufficient alone but enhances virus replication.

Location specific small RNA annealing to the HCV 5’ UTR promotes Hepatitis C Virus replication by favoring IRES formation and stimulating virus translation

ABSTRACTHepatitis C virus (HCV) genome replication requires annealing of a liver specific small-RNA, miR-122 to 2 sites on 5’ untranslated region (UTR). Annealing has been reported to a) stabilize the genome, b) promote translation, and c) induce the canonical HCV 5’ UTR Internal Ribosome Entry Site (IRES) structure. In this report we identify the relative impact of small RNA annealing on the three functions ascribed to miR-122 and generate a mechanistic model for miR-122 promotion of HCV. First, we identified that perfectly complementary small RNAs that anneal to different locations on the HCV 5’ UTR stimulate replication with varying efficiencies and mapped the region on the HCV genome to which small RNA annealing promotes virus replication. Second, by using a panel of small RNAs that promote with varying efficiencies we link HCV replication induction with translation stimulation and 5’ UTR RNA structure modifications. However, replication promotion was not linked to genome stabilization since all small RNAs tested could stabilize the viral genome regardless of their ability to promote replication. Thus, we propose that miR-122 annealing promotes HCV replication primarily by activating the HCV IRES and stimulating translation, and that miR-122-induced HCV genome stabilization is insufficient alone but enhances virus replication.Graphical Abstract

Reciprocal interactions between mtDNA and lifespan control in budding yeast

Loss of mitochondrial DNA (mtDNA) results in loss of mitochondrial respiratory activity, checkpoint-regulated inhibition of cell cycle progression, defects in growth, and nuclear genome instability. However, after several generations, yeast cells can adapt to the loss of mtDNA. During this adaptation, rho0 cells, which have no mtDNA, exhibit increased growth rates and nuclear genome stabilization. Here, we report that an immediate response to loss of mtDNA is a decrease in replicative lifespan (RLS). Moreover, we find that adapted rho0 cells bypass the mtDNA inheritance checkpoint, exhibit increased mitochondrial function, and undergo an increase in RLS as they adapt to the loss of mtDNA. Transcriptome analysis reveals that metabolic reprogramming to compensate for defects in mitochondrial function is an early event during adaptation and that up-regulation of stress response genes occurs later in the adaptation process. We also find that specific subtelomeric genes are silenced during adaptation to loss of mtDNA. Moreover, we find that deletion of SIR3, a subtelomeric gene silencing protein, inhibits silencing of subtelomeric genes associated with adaptation to loss of mtDNA, as well as adaptation-associated increases in mitochondrial function and RLS extension.