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Mouse models are central to studying and understanding the genotypic‐to‐phenotypic outcomes of Down syndrome (DS), a complex condition caused by an extra copy of the long arm of human chromosome 21. The recently developed TcMAC21—a transchromosomic mouse strain with comparable gene dosage to human chromosome 21 (Hsa21)—includes more Hsa21 genes than any other model of DS. Recent studies on TcMAC21 have provided valuable insight into the molecular, physiological, and neuroanatomical aspects of the model. However, relatively little is known about the craniofacial phenotype of TcMAC21 mice, particularly as it compares to the widely studied Ts65Dn model. Here we conducted a quantitative study of the cranial morphology of TcMAC21 and Ts65Dn mice and their respective unaffected littermates. Our comparative data comprise forty three‐dimensional cranial measurements taken on micro‐computed tomography scans of the heads of TcMAC21 and Ts65Dn mice. Our results show that TcMAC21 exhibit similar patterns of craniofacial change to Ts65Dn. However, the DS‐specific morphology is more pronounced in Ts65Dn mice. Specifically, Ts65Dn present with more medio‐lateral broadening and retraction of the snout compared to TcMAC21. Our findings reveal the complexity of potential gene interaction in the production of craniofacial phenotypes. [ABSTRACT FROM AUTHOR]

Gene duplication is seen as a major source of structural and functional divergence in genome evolution. Under the conventional models of sub or neofunctionalization, functional changes arise in one of the duplicates after duplication. However, we suggest here that the presence of a duplicated gene can result in functional changes to its interacting partners. We explore this hypothesis by in silico evolution of a heterodimer when one member of the interacting pair is duplicated. We examine how a range of selection pressures and protein structures leads to differential patterns of evolutionary divergence. We find that a surprising number of distinct evolutionary trajectories can be observed even in a simple three member system. Further, we observe that selection to correct dosage imbalance can affect the evolution of the initial function in several unexpected ways. For example, if a duplicate is under selective pressure to avoid binding its original binding partner, this can lead to changes in the binding interface of a nonduplicated interacting partner to exclude the duplicate. Hence, independent of the fate of the duplicate, its presence can impact how the original function operates. Additionally, we introduce a conceptual framework to describe how interacting partners cope with dosage imbalance after duplication. Contextualizing our results within this framework reveals that the evolutionary path taken by a duplicate's interacting partners is highly stochastic in nature. Consequently, the fate of duplicate genes may not only be controlled by their own ability to accumulate mutations but also by how interacting partners cope with them. [ABSTRACT FROM AUTHOR]

Successful generation of pentaploid wheat (genome, BBAAD) via interspecific hybridization between tetraploid wheat (BBAA) and hexaploid wheat (BBAADD) holds great promise to mutually exchange desirable traits between the two cultivated wheat species, as well as providing a novel facet for evolutionary studies of polyploid wheat. Taking advantage of the viable and fertile nature of an extracted tetraploid wheat (ETW) with a BBAA genome that is virtually identical with the BBAA component of a hexaploid common wheat, and a synthetic hexaploid wheat, we constructed four pentaploid wheats with several distinct yet complementary features, of which harboring homozygous BBAA subgenomes is a common feature. By using a combined FISH/GISH method that enables diagnosing all individual wheat chromosomes, we precisely karyotyped a larger number of cohorts from the immediate progenies of each of the four pentaploid wheats. We found that the BBAA component of hexaploid common wheat possesses a significantly stronger capacity to buffer and sustain imbalanced D genome chromosomes and appears to harbor more structural chromosome variations than the BBAA genome of tetraploid wheat. We also document that this stronger capacity of the hexaploid BBAA subgenomes behaves as a genetically controlled dominant trait. Our findings bear implications to the known greater than expected level of genetic diversity in, and the remarkable adaptability of, hexaploid common wheat as a staple crop of global significance, as well as in using pentaploidy as intermediates for reciprocal introgression of useful traits between tetraploid and hexaploid wheat cultivars. [ABSTRACT FROM AUTHOR]

Gene/genome dosage balance is an essential evolutionary mechanism for organisms to ensure a normal function, but the underlying causes of dosage-imbalance regulation remain poorly understood. Herein, the serial Brassica hybrids/polyploids (AC, AAC, CCA, CCAA) with different copies of A and C subgenomes from the same two parents of Brassica rapa and Brassica oleracea were synthesized to investigate the effects of genome dosages on gene expressions and interactions by using RNA-Seq. The expression changes of A- and C-subgenome genes were consistent with dosage alterations. Dosage-dependent and -independent genes were grouped according to the correlations between dosage variations and gene expressions. Expression levels of dosage-dependent genes were strongly correlated with dosage changes and mainly contributed to dosage effects, while those of dosage-independent genes gave weak correlations with dosage variations and mostly facilitated dosage compensation. More protein–protein interactions were detected for dosage-independent genes than dosage-dependent ones, as predicted by the dosage balance hypothesis. Dosage-dependent genes more likely impacted the expressions by trans effects, whereas dosage-independent genes preferred to play by cis effects. Furthermore, dosage-dependent genes were mainly associated with the basic biological processes to maintain the stability of the growth and development, while dosage-independent genes were more enriched in the stress response related processes to accelerate adaptation. The present comprehensive analysis of gene expression dependent/independent on dosage alterations in Brassica polyploids provided new insights into gene/genome dosage-imbalance regulation of gene expressions. [ABSTRACT FROM AUTHOR]

Background: Down syndrome (DS; trisomy 21) is the most common genetic cause of mental retardation in the human population and key molecular networks dysregulated in DS are still unknown. Many different experimental techniques have been applied to analyse the effects of dosage imbalance at the molecular and phenotypical level, however, currently no integrative approach exists that attempts to extract the common information. Results: We have performed a statistical meta-analysis from 45 heterogeneous publicly available DS data sets in order to identify consistent dosage effects from these studies. We identified 324 genes with significant genome-wide dosage effects, including well investigated genes like SOD1, APP, RUNX1 and DYRK1A as well as a large proportion of novel genes (N = 62). Furthermore, we characterized these genes using gene ontology, molecular interactions and promoter sequence analysis. In order to judge relevance of the 324 genes for more general cerebral pathologies we used independent publicly available microarry data from brain studies not related with DS and identified a subset of 79 genes with potential impact for neurocognitive processes. All results have been made available through a web server under http://ds-geneminer.molgen.mpg.de/. Conclusions: Our study represents a comprehensive integrative analysis of heterogeneous data including genome-wide transcript levels in the domain of trisomy 21. The detected dosage effects build a resource for further studies of DS pathology and the development of new therapies. [ABSTRACT FROM AUTHOR]

Background: Great advances have been achieved in our understanding of flower development and evolution since the establishment of the ABC model. However, it remains a challenge to define the exact context of organ identity in the component interactions of the ABC model. Results: Through hybridization, we detected a homeotic mutant in Petrocosmea (Gesneriaceae) uniquely displayed by the 'petaloid-stamen' in the third whorl with petal identity. Comparative Real-time PCR analyses demonstrate that both two B-class genes DEF2 and GLO are excessively expressed while the transcripts of the C-class gene PLE are reduced in the third floral whorl in the mutant compared to that in the wild-type F1 hybrids. Further allele-specific expression (ASE) analyses indicate that an allele-specific change in PgPLE might be responsible for up-regulation of both B-class genes and down-regulation of the C-class gene in the petaloid-stamen mutants. Conclusions: Our findings suggest that the petaloid-stamen is consequent upon an evident dosage imbalance between B- and C-class products that is probably triggered by a cis-regulatory change. In addition, the genetic pathway for the floral organ identity might be in parallel with that for the floral symmetry. The extreme variation in hybrids further suggests that interspecific hybridization may represent a major factor for evolutionary innovation and diversification in plants. [ABSTRACT FROM AUTHOR]