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Abstract Background The genetic architecture of complex traits strongly influences the consequences of inherited mutations, genetic engineering, environmental and genetic perturbations, and natural and artificial selection. But because most studies are under-powered, the picture of complex traits is often incomplete. Chromosome substitution strains (CSSs) are a unique paradigm for these genome surveys because they enable statistically independent, powerful tests for the phenotypic effects of each chromosome on a uniform inbred genetic background. A previous CSS survey in mice and rats revealed many complex trait genes (QTLs), large phenotypic effects, extensive epistasis, as well as systems properties such as strongly directional phenotypic changes and genetically-determined limits on the range of phenotypic variation. However, the unusually close genetic relation between the CSS progenitor strains in that study raised questions about the impact of genetic divergence: would greater divergence between progenitor strains, with the corresponding changes in gene regulation and protein function, lead to significantly more distinctive phenotypic features, or alternatively would epistasis and systems constraints, which are pervasive in CSSs, limit the range of phenotypic variation regardless of the extent of DNA sequence variation? Results We analyzed results for an extensive survey of traits in two new panels of CSSs where the donor strains were derived from inbred strains with more distant origins and discovered a strong similarity in genetic and systems properties among the three CSS panels, regardless of divergence time. Conclusion Our results argue that DNA sequence differences between host and donor strains did not substantially affect the architecture of complex traits, and suggest instead that strong epistasis buffered the phenotypic effects of genetic divergence, thereby constraining the range of phenotypic variation.

Abstract Background High-density short oligonucleotide microarrays are useful tools for studying biodiversity, because they can be used to investigate both nucleotide and expression polymorphisms. However, when different strains (or species) produce different signal intensities after mRNA hybridization, it is not easy to determine whether the signal intensities were affected by nucleotide or expression polymorphisms. To overcome this difficulty, nucleotide and expression polymorphisms are currently examined separately. Results We have developed SNEP, a new method that allows simultaneous detection of both nucleotide and expression polymorphisms. SNEP involves a robust statistical procedure based on the idea that a nucleotide polymorphism observed at the probe level can be regarded as an outlier, because the nucleotide polymorphism can reduce the hybridization signal intensity. To investigate the performance of SNEP, we used three species: barley, rice and mice. In addition to the publicly available barley data, we obtained new rice and mouse data from the strains with available genome sequences. The sensitivity and false positive rate of nucleotide polymorphism detection were estimated based on the sequence information. The robustness of expression polymorphism detection against nucleotide polymorphisms was also investigated. Conclusion SNEP performed well regardless of the genome size and showed a better performance for nucleotide polymorphism detection, when compared with other previously proposed methods. The R-software 'SNEP' is available at http://www.ism.ac.jp/~fujisawa/SNEP/.

Inflammasomes are innate immune mechanisms that activate caspase‐1 in response to a variety of stimuli, including Salmonella infection. Active caspase‐1 has a potential to induce two different types of cell death, depending on the expression of the pyroptosis mediator gasdermin D (GSDMD); following caspase‐1 activation, GSDMD‐sufficient and GSDMD‐null/low cells undergo pyroptosis and apoptosis, respectively. Although Bid, a caspase‐1 substrate, plays a critical role in caspase‐1 induction of apoptosis in GSDMD‐null/low cells, an additional mechanism that mediates this cell death independently of Bid has also been suggested. This study investigated the Bid‐independent pathway of caspase‐1‐induced apoptosis. Caspase‐1 has been reported to process caspase‐6 and caspase‐7. Silencing of caspase‐7, but not caspase‐6, significantly reduced the activation of caspase‐3 induced by caspase‐1, which was activated by chemical dimerization, in GSDMD/Bid‐deficient cells. CRISPR/Cas9‐mediated depletion of caspase‐7 had the same effect on the caspase‐3 activation. Moreover, in the absence of GSDMD and Bid, caspase‐7 depletion reduced apoptosis induced by caspase‐1 activation. Caspase‐7 was activated following caspase‐1 activation independently of caspase‐3, suggesting that caspase‐7 acts downstream of caspase‐1 and upstream of caspase‐3. Salmonella induced the activation of caspase‐3 in GSDMD‐deficient macrophages, which relied partly on Bid and largely on caspase‐1. The caspase‐3 activation and apoptotic morphological changes seen in Salmonella‐infected GSDMD/Bid‐deficient macrophages were attenuated by caspase‐7 knockdown. These results suggest that in addition to Bid, caspase‐7 can also mediate caspase‐1‐induced apoptosis and provide mechanistic insights into inflammasome‐associated cell death that is one major effector mechanism of inflammasomes. [ABSTRACT FROM AUTHOR]

Summary: Inflorescence architecture is diverse in angiosperms, and is mainly determined by the arrangement of the branches and flowers, known as phyllotaxy. In rice (Oryza sativa), the main inflorescence axis, called the rachis, generates primary branches in a spiral phyllotaxy, and flowers (spikelets) are formed on these branches. Here, we have studied a classical mutant, named verticillate rachis (ri), which produces branches in a partially whorled phyllotaxy. Gene isolation revealed that RI encodes a BELL1‐type homeodomain transcription factor, similar to Arabidopsis PENNYWISE/BELLRINGER/REPLUMLESS, and is expressed in the specific regions within the inflorescence and branch meristems where their descendant meristems would soon initiate. Genetic combination of an ri homozygote and a mutant allele of RI‐LIKE1 (RIL1) (designated ri ril1/+ plant), a close paralog of RI, enhanced the ri inflorescence phenotype, including the abnormalities in branch phyllotaxy and rachis internode patterning. During early inflorescence development, the timing and arrangement of primary branch meristem (pBM) initiation were disturbed in both ri and ri ril1/+ plants. These findings suggest that RI and RIL1 were involved in regulating the phyllotactic pattern of the pBMs to form normal inflorescences. In addition, both RI and RIL1 seem to be involved in meristem maintenance, because the ri ril1 double‐mutant failed to establish or maintain the shoot apical meristem during embryogenesis. Significance Statement: We revealed that two BELL1‐like genes, RI and RIL1, play a crucial role in elaborating inflorescence architecture by regulating the timing and arrangement of primary branch meristem initiation. In addition, we suggest that these genes are also involved in meristem maintenance. [ABSTRACT FROM AUTHOR]