Brassinosteroids (BRs) are phytosteroid hormones controlling various physiological processes critical for normal growth and development. BRs are perceived by a protein complex containing two transmembrane receptor kinases, BRASSINOSTEROID INSENSITIVE 1 (BRI1) and BRI1-ASSOCIATED RECEPTOR KINASE 1 (BAK1) [1-3]. BRI1 null mutants exhibit a dwarfed stature with epinastic leaves, delayed senescence, reduced male fertility, and altered light responses. BAK1 null mutants, however, only show a subtle phenotype, suggesting that functionally redundant proteins might be present in the Arabidopsis genome. Here we report that BAK1-LIKE 1 (BKK1) functions redundantly with BAK1 in regulating BR signaling. Surprisingly, rather than the expected bri1-like phenotype, bak1 bkk1 double mutants exhibit a seedling-lethality phenotype due to constitutive defense-gene expression, callose deposition, reactive oxygen species (ROS) accumulation, and spontaneous cell death even under sterile growing conditions. Our detailed analyses demonstrate that BAK1 and BKK1 have dual physiological roles: positively regulating a BR-dependent plant growth pathway, and negatively regulating a BR-independent cell-death pathway. Both BR signaling and developmentally controlled cell death are critical to optimal plant growth and development, but the mechanisms regulating early events in these pathways are poorly understood. This study provides novel insights into the initiation and crosstalk of the two signaling cascades.

The concept of orthology provides a foundation for formulating hypotheses on gene and genome evolution, and thus forms the cornerstone of comparative genomics, phylogenomics and metagenomics. We present the update of OrthoDB—the hierarchical catalog of orthologs (http://www.orthodb.org). From its conception, OrthoDB promoted delineation of orthologs at varying resolution by explicitly referring to the hierarchy of species radiations, now also adopted by other resources. The current release provides comprehensive coverage of animals and fungi representing 252 eukaryotic species, and is now extended to prokaryotes with the inclusion of 1115 bacteria. Functional annotations of orthologous groups are provided through mapping to InterPro, GO, OMIM and model organism phenotypes, with cross-references to major resources including UniProt, NCBI and FlyBase. Uniquely, OrthoDB provides computed evolutionary traits of orthologs, such as gene duplicability and loss profiles, divergence rates, sibling groups, and now extended with exon–intron architectures, syntenic orthologs and parent–child trees. The interactive web interface allows navigation along the species phylogenies, complex queries with various identifiers, annotation keywords and phrases, as well as with gene copy-number profiles and sequence homology searches. With the explosive growth of available data, OrthoDB also provides mapping of newly sequenced genomes and transcriptomes to the current orthologous groups.

Six measures of evolutionary change in the human genome were studied, three derived from the aligned human and mouse genomes in conjunction with the Mouse Genome Sequencing Consortium, consisting of (1) nucleotide substitution per fourfold degenerate site in coding regions, (2) nucleotide substitution per site in relics of transposable elements active only before the human–mouse speciation, and (3) the nonaligning fraction of human DNA that is nonrepetitive or in ancestral repeats; and three derived from human genome data alone, consisting of (4) SNP density, (5) frequency of insertion of transposable elements, and (6) rate of recombination. Features 1 and 2 are measures of nucleotide substitutions at two classes of “neutral” sites, whereas 4 is a measure of recent mutations. Feature 3 is a measure dominated by deletions in mouse, whereas 5 represents insertions in human. It was found that all six vary significantly in megabase-sized regions genome-wide, and many vary together. This indicates that some regions of a genome change slowly by all processes that alter DNA, and others change faster. Regional variation in all processes is correlated with, but not completely accounted for, by GC content in human and the difference between GC content in human and mouse. [Supplemental material is available online at www.genome.org and http://www.soe.ucsc.edu/research/compbio/covariation/.

BackgroundAn emerging cavefish model, the cyprinid genus Sinocyclocheilus, is endemic to the massive southwestern karst area adjacent to the Qinghai-Tibetan Plateau of China. In order to understand whether orogeny influenced the evolution of these species, and how genomes change under isolation, especially in subterranean habitats, we performed whole-genome sequencing and comparative analyses of three species in this genus, S. grahami, S. rhinocerous and S. anshuiensis. These species are surface-dwelling, semi-cave-dwelling and cave-restricted, respectively.ResultsThe assembled genome sizes of S. grahami, S. rhinocerous and S. anshuiensis are 1.75 Gb, 1.73 Gb and 1.68 Gb, respectively. Divergence time and population history analyses of these species reveal that their speciation and population dynamics are correlated with the different stages of uplifting of the Qinghai-Tibetan Plateau. We carried out comparative analyses of these genomes and found that many genetic changes, such as gene loss (e.g. opsin genes), pseudogenes (e.g. crystallin genes), mutations (e.g. melanogenesis-related genes), deletions (e.g. scale-related genes) and down-regulation (e.g. circadian rhythm pathway genes), are possibly associated with the regressive features (such as eye degeneration, albinism, rudimentary scales and lack of circadian rhythms), and that some gene expansion (e.g. taste-related transcription factor gene) may point to the constructive features (such as enhanced taste buds) which evolved in these cave fishes.ConclusionAs the first report on cavefish genomes among distinct species in Sinocyclocheilus, our work provides not only insights into genetic mechanisms of cave adaptation, but also represents a fundamental resource for a better understanding of cavefish biology.Electronic supplementary materialThe online version of this article (doi:10.1186/s12915-015-0223-4) contains supplementary material, which is available to authorized users.

CorrectionsBIOCHEMISTRY. For the article ''Arg-302 facilitates deprotonation of Glu-325 in the transport mechanism of the lactose permease from Escherichia coli'' by Miklós Sahin-Tóth and H. Ronald Kaback, which appeared in number 11, May 22, 2001, of Proc. Natl. Acad. Sci. USA (98, 6068 -6073; First Published May 15, 2001; 10.1073͞pnas.111139698), Fig. 1 was printed incorrectly due to a printer's error. The correct figure and its legend appear below.www.pnas.org͞cgi͞doi͞10.1073͞pnas.151252598 Fig. 1.Model for H ϩ translocation during lactose͞H ϩ symport via lac permease. For clarity, 6 of the 12 helices that compose the permease are shown. The gray area designates the low dielectric environment of the lipid bilayer. (A) In the ground-state conformation, the relevant H ϩ is shared by His-322 (helix X) and Glu-269 (helix VIII), whereas Arg-302 (helix IX) is charge-paired with Glu-325 (helix X). In this conformation, lac permease binds substrate with high affinity at the outer surface (S o ). Glu-126 (helix IV) and Arg-144 (helix V) are charge-paired and represent the major components of the substrate-binding site. Also shown is the charge-pair between Asp-240 (helix VII) and Lys-319 (helix X), which are not essential for the mechanism. (B) Substrate binding induces a conformational change that disrupts the E269͞H322 and R302͞E325 charge-pairs and leads to the transfer of the H ϩ to Glu-325, now stabilized by the low dielectric environment. At the same time, the substrate-binding site becomes exposed to the inner surface of the membrane (S i ). After substrate dissociation, Glu-325 deprotonates at the inside surface (because of the rejuxtaposition of Glu-325 with Arg-302) as the permease relaxes back to the ground-state conformation.

Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers’ tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates.

BackgroundTransmembrane receptor kinases play critical roles in both animal and plant signaling pathways regulating growth, development, differentiation, cell death, and pathogenic defense responses. In Arabidopsis thaliana, there are at least 223 Leucine-rich repeat receptor-like kinases (LRR-RLKs), representing one of the largest protein families. Although functional roles for a handful of LRR-RLKs have been revealed, the functions of the majority of members in this protein family have not been elucidated.ResultsAs a resource for the in-depth analysis of this important protein family, the complementary DNA sequences (cDNAs) of 194 LRR-RLKs were cloned into the GatewayR donor vector pDONR/ZeoR and analyzed by DNA sequencing. Among them, 157 clones showed sequences identical to the predictions in the Arabidopsis sequence resource, TAIR8. The other 37 cDNAs showed gene structures distinct from the predictions of TAIR8, which was mainly caused by alternative splicing of pre-mRNA. Most of the genes have been further cloned into GatewayR destination vectors with GFP or FLAG epitope tags and have been transformed into Arabidopsis for in planta functional analysis. All clones from this study have been submitted to the Arabidopsis Biological Resource Center (ABRC) at Ohio State University for full accessibility by the Arabidopsis research community.ConclusionsMost of the Arabidopsis LRR-RLK genes have been isolated and the sequence analysis showed a number of alternatively spliced variants. The generated resources, including cDNA entry clones, expression constructs and transgenic plants, will facilitate further functional analysis of the members of this important gene family.

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