Genes & genetic systems最新文献

Many sex-determining genes (SDGs) were generated as neofunctionalized genes through duplication and/or mutation of gonadal formation-related genes. We previously identified dm-W as an SDG in the African clawed frog Xenopus laevis and found that a partial duplication of the masculinization gene dmrt1 created the neofunctionalized dm-W after allotetraploidization by interspecific hybridization. The allotetraploid Xenopus species have two dmrt1 genes, dmrt1.L and dmrt1.S. Xenopus laevis dm-W has four exons: two dmrt1.S-derived exons (exons 2 and 3) and two other exons (noncoding exon 1 and exon 4). Our recent work revealed that exon 4 originated from a DNA transposon, hAT-10. Here, to clarify when and how the noncoding exon 1 and its coexisting promoter evolved during the establishment of dm-W after allotetraploidization, we newly determined nucleotide sequences of the dm-W promoter region from two other allotetraploid species, X. largeni and X. petersii, and performed an evolutionary analysis. We found that dm-W acquired a new exon 1 and TATA-type promoter in the common ancestor of the three allotetraploid Xenopus species, resulting in the deletion of the dmrt1.S-derived TATA-less promoter. In addition, we demonstrated that the TATA box contributes to dm-W promoter activity in cultured cells. Collectively, these findings suggest that this novel TATA-type promoter was important for the establishment of dm-W as a sex-determining gene, followed by the degeneration of the preexisting promoter.

Cichlid fishes are textbook examples of explosive speciation and adaptive radiation, providing a great opportunity to understand how the genomic substrate yields extraordinary species diversity. Recently, we performed comparative genomic analyses of three Lake Victoria cichlids to reveal the genomic substrates underlying their rapid speciation and adaptation. We found that long divergent haplotypes derived from large-scale standing genetic variation, which originated before the adaptive radiation of Lake Victoria cichlids, may have contributed to their rapid diversification. In addition, the present study on genomic data from other East African cichlids suggested the reuse of alleles that may have originated in the ancestral lineages of Lake Tanganyika cichlids during cichlid evolution. Therefore, our results highlight that the primary factor that could drive repeated adaptive radiation across East African cichlids was allelic reuse from standing genetic variation to adapt to their own specific environment. In this report, we summarize the main results and discuss the evolutionary mechanisms of cichlids, based on our latest findings.

Members of a plant-specific BES/BZR transcription factor (TF) family including BRI1-EMS-SUPPRESSOR 1 (BES1) and BRASSINAZOLE-RESISTANT 1 (BZR1) regulate various developmental processes and environmental responses. Recently, we reported that BES1/BZR1 Homolog 3 (BEH3) exhibited a competitive effect toward other BES/BZR TFs. In this study, we analyzed transcriptome profiles in BEH3-overexpressing plants and compared them with those of BES1 and BZR1 double gain-of-function mutants. We identified 46 differentially expressed genes (DEGs), which were downregulated in the gain-of-function mutants of BES1 and BZR1 but upregulated upon BEH3 overexpression. In these DEGs, putative BES1 and BZR1 direct-targeted genes were highly enriched. In addition, these DEGs contained not only known brassinosteroid biosynthetic enzymes, but also some NAC TFs, which negatively regulate brassinosteroid-inactivating enzymes. Moreover, the iron sensor and the iron-deficient response-related bHLH TFs were also included. Taken together, our findings indicate that a competitive relationship between BEH3 and other BES/BZR TFs exists in various BES/BZR binding target genes.

Meiotic recombination between homologous chromosomes is promoted by the collaborative action of two RecA homologs, Rad51 and meiosis-specific Dmc1. The filament assembly of Dmc1 is promoted by meiosis-specific Mei5-Sae3 in budding yeast. Mei5-Sae3 shows sequence similarity to fission yeast Sfr1-Swi5, which stimulates DNA strand exchanges by Rad51 as well as Dmc1. Sae3 and Swi5 share a conserved motif with the amino acid sequence YNEI/LK/RD. In this study, we analyzed the role of the YNEL residues in the Sae3 sequence in meiotic recombination and found that these residues are critical for Sae3 function in Dmc1 assembly. L59 substitution in the Sae3 protein disrupts complex formation with Mei5, while Y56 and N57 substitutions do not. These observations reveal the differential contribution of conserved YNEL residues to Sae3 activities in meiotic recombination.

Posttranslational modifications (PTMs) to proteins are regulatory mechanisms that play a critical role in regulating growth and development. The SUMO system is a rapid and dynamic PTM system employed by eukaryotic cells. Plant SUMOs are involved in many physiological processes, such as stress responses, regulation of flowering time and defense reactions to pathogen attack. In Arabidopsis thaliana and rice (Oryza sativa), eight and seven SUMO genes, respectively, were predicted by sequence analysis. Phylogenetic tree analysis of these SUMOs shows that they are divided into two groups. One consists of SUMOs that contain no SUMO acceptor site and are involved in monoSUMOylation of their target proteins. Rice OsSUMO1 and OsSUMO2 are in this group, and are structurally similar to each other and to Arabidopsis AtSUMO1. The other group is composed of SUMOs in which an acceptor site (ΨKXE/D) occurs inside the SUMO molecule, suggesting their involvement in polySUMOylation. Several studies on the rice SUMOs have been performed independently and reported. Individual names of rice SUMOs are confusing, because a unified nomenclature has not been proposed. This review clarifies the attribution of seven rice SUMOs and unifies the individual SUMO names.

Southeast Asia supports high biodiversity, in a mosaic of forest types formed by the expansion and contraction of habitats through past climate changes. Among the region's forest types, the geographical distribution of peat swamp forests has fluctuated intensely over the past 120,000 years. Most peat swamp forests in Southeast Asia are found in coastal regions and formed within the last 7,000 years after a decline in sea level. However, some peat swamps were initiated earlier on substrates of slightly higher elevation, and these peat swamps might have been refugia for peat swamp species in the last glacial period and the high sea level period. We assessed genetic diversity, genetic structure and divergence time of current genetic groups for Shorea albida in Brunei, an endemic tree species of Bornean peat swamp forests, using 18 microsatellite markers. Genetic diversity was not lower than has been found in other Shorea species, possibly because of the high density of S. albida in Brunei. Although overall genetic divergence between populations was low, two populations (Ingei and Labi Road 3) were distinct from the other populations. Analysis using DIYABC estimated that three genetic groups (Ingei, Labi Road 3 and others) diverged simultaneously from their ancestral population, whose effective size was very small, about 7,500 years ago, corresponding to a recent sea level peak in the Belait-Baram river basin. In that high sea level period, some higher-elevation lands remained, and peat formation had already started in this region. We propose that the current genetic structure of S. albida in Brunei was formed from small refugial populations that survived the period of higher sea level in these higher-elevation areas. Because of their relatively high genetic diversity, Brunei's S. albida populations should become an important genetic resource for the recovery of genetically healthy populations in other parts of northwest Borneo.

Plaque vulnerability is associated with the degree of carotid artery stenosis (CS) and the risk of stroke. MicroRNAs (miRNAs) exert critical functions in disease progression, although only a few miRNAs have been well identified in CS. Therefore, this study aimed to investigate the differential expression profile of miRNAs and their potential functions in plaques of CS patients. Three CS patients with stable plaques and three patients with vulnerable plaques who underwent carotid endarterectomy were enrolled in this study. Differentially expressed miRNAs (DEmiRNAs) between patients with stable and vulnerable plaques were determined using small RNA sequencing. Target genes of DEmiRNAs were predicted and submitted to functional analyses. Validation of dysregulated DEmiRNAs was determined using quantitative real-time polymerase chain reaction (qRT-PCR). After sequencing, 76 DEmiRNAs were identified in vulnerable plaques, including 53 upregulated miRNAs and 23 downregulated miRNAs. Next, 23,495 target genes of the identified DEmiRNAs were predicted and functionally analyzed. This indicated that the target genes of the identified DEmiRNAs were mainly enriched in protein phosphorylation, transcription, nitrogen compound metabolism, endocytosis and autophagy, and related to signaling pathways of Hippo, MAPK, insulin, TGF-β, FoxO, AMPK and p53. Furthermore, qRT-PCR results for six miRNAs showed that five (83%) of them (hsa-miR-511-5p, hsa-miR-150-5p, hsa-miR-378a-5p, hsa-miR-365b-5p and hsa-miR-6511b-5p) were consistent with the sequencing results. Differential expression profiles and potential function of miRNAs associated with plaque stability in CS patients are identified for the first time, which should help to understand the regulatory mechanism of plaque stability in CS.

Mechanisms underlying how the genetic code was generated by Darwinian selection have remained elusive since the code was cracked in 1965. Here, I propose a hypothesis on the emergence of the genetic code and predict that its emergence was driven by sequential distinct selective pressures. According to the hypothesis, aminoacyl-RNAs for Glu, Asp, Lys, Tyr, His, Arg, Cys and Ser were first selected as cartridge-type subunits of three-subunit ribozymes. Aminoacyl-RNA subunits acting as cofactors were accommodated by the proto P-site of the large subunit of ribozymes. Importantly, I predict that there was no direct relationship between amino acids and codon and anticodon pairs. Duplication of the proto P-site could have created the proto A-site, enabling multi-subunit ribozymes to simultaneously interact with two-cartridge-type aminoacyl-RNA subunits. Random insertion of two cartridges would have instantly abolished enzymatic activity of multi-subunit ribozymes. On the other hand, if two tandemly aligned pairs of codons and anticodons specify two cartridges, dozens of different active pockets in multi-subunit ribozymes would have rapidly emerged, leading to the rise of extant organisms' metabolic pathways. The strong driving force of Darwinian selection described here could have created the primary genetic code for catalytic amino acids. Evolution of the protein translation system and events leading to the expansion of the genetic code until the time it was "frozen" are presented in detail.

Liver cancer is highly heterogeneous and has a poor prognosis. We aimed to identify a drug metabolism-related prognostic subtype and a gene signature as references for prognosis and therapy options for patients with liver cancer. Patient information was collected from online databases. Drug metabolism-related genes were obtained from previous studies and were used to screen differentially expressed prognostic genes. The patients were divided into different clusters and differences in clinical features, immunity, pathways and therapy responses between the clusters were analyzed. LASSO analysis was performed to identify the optimal prognostic genes and establish a risk score model. Finally, the risk score distribution in different subtypes was investigated. A total of 54 prognostic genes were identified to categorize the patients into cluster 1 and cluster 2. Cluster 1 showed worse survival than cluster 2, and cluster 1 also showed high levels of malignancy. Furthermore, cluster 1 exhibited a higher TIDE (tumor immune dysfunction and exclusion) score and lower IC50 response to paclitaxel, gemcitabine and camptothecin, indicating that cluster 1 individuals may derive more benefit from immunotherapy but less benefit from chemotherapy. The risk score, based on the six optimal prognostic genes, demonstrated an adequate prognostic capability. The high-risk group showed worse survival; meanwhile, cluster 1 contained the majority of high-risk samples. Our results should be useful for prognosis and specific therapy for patients with liver cancer. Patients with the features of cluster 1 and a high risk score will tend to exhibit worse survival. Furthermore, immunotherapy may be more suitable for cluster 1-type patients while chemotherapy may be more suitable for cluster 2 patients.

Genome instability is a major cause of aging. In the budding yeast Saccharomyces cerevisiae, instability of the ribosomal RNA gene repeat (rDNA) is known to shorten replicative lifespan. In yeast, rDNA instability in an aging cell is associated with accumulation of extrachromosomal rDNA circles (ERCs) which titrate factors critical for lifespan maintenance. ERC accumulation is not detected in mammalian cells, where aging is linked to DNA damage. To distinguish effects of DNA damage from those of ERC accumulation on senescence, we re-analyzed a yeast strain with a replication initiation defect in the rDNA, which limits ERC multiplication. In aging cells of this strain (rARS-∆3) rDNA became unstable, as in wild-type cells, whereas significantly fewer ERCs accumulated. Single-cell aging analysis revealed that rARS-∆3 cells follow a linear survival curve and can have a wild-type replicative lifespan, although a fraction of the cells stopped dividing earlier than wild type. The doubling time of rARS-∆3 cells appears to increase in the final cell divisions. Our results suggest that senescence in rARS-∆3 is linked to the accumulation of DNA damage as in mammalian cells, rather than to elevated ERC level. Therefore, this strain should be a good model system to study ERC-independent aging.