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Protein evolution rate is negatively correlated with several effectors, such as expression level, expression distribution, protein–protein interactions (PPIs), and essentiality for survival. These effectors can characterize the signaling pathways mediated by ligand‐receptor binding. However, it is unclear whether these effectors are constraining factors on the pathway‐specific evolution of ligands and receptors. To clarify the relation between the effectors and protein evolution (dN/dS ratio) in ligands and their receptors considering each signaling pathway, we investigated 377 proteins in 20 peptide/protein ligand groups and their receptor groups using 15 primate sequences. The dN/dS ratios between peptide/protein ligand groups and their receptor groups were positively correlated, suggesting the protein evolution under the influence of signaling pathway to which they belong. Comparing each signaling pathway, ligands and receptors mainly related to development and growth (FGF/Hedgehog/Notch/WNT groups) showed lower dN/dS ratios, higher PPI numbers, and higher essentiality, whereas those mainly related to immune process (CSF/IFN/IL/TNF groups) showed higher dN/dS ratios, lower PPI numbers, and lower essentiality. Most ligands and receptors were poorly expressed, and expression level was not a constraining factor on the protein evolution. These findings indicate that PPI and essentiality are constraining factors that characterize the pathway‐specific evolution of ligands and receptors. [ABSTRACT FROM AUTHOR]

Sex chromosomes in poikilothermal vertebrates are characterized by rapid and diverse evolution at the species or population level. Our previous study revealed that the Taiwanese frog Odorrana swinhoana (2n = 26) has a unique system of multiple sex chromosomes created by three sequential translocations among chromosomes 1, 3, and 7. To reveal the evolutionary history of sex chromosomes in the Odorrana species complex, we first identified the original, homomorphic sex chromosomes, prior to the occurrence of translocations, in the ancestral‐type population of O. swinhoana. Then, we extended the investigation to a closely related Japanese species, Odorrana utsunomiyaorum, which is distributed on two small islands. We used a high‐throughput nuclear genomic approach to analyze single‐nucleotide polymorphisms and identify the sex‐linked markers. Those isolated from the O. swinhoana ancestral‐type population were found to be aligned to chromosome 1 and showed male heterogamety. In contrast, almost all the sex‐linked markers isolated from O. utsunomiyaorum were heterozygous in females and homozygous in males and were aligned to chromosome 9. Morphologically, we confirmed chromosome 9 to be heteromorphic in females, showing a ZZ‐ZW sex determination system, in which the W chromosomes were heterochromatinized in a stripe pattern along the chromosome axis. These results indicated that after divergence of the two species, the ancestral homomorphic sex chromosome 1 underwent highly rapid and diverse evolution, i.e., sequential translocations with two autosomes in O. swinhoana, and turnover to chromosome 9 in O. utsunomiyaorum, with a transition from XY to ZW heterogamety and change to heteromorphy. [ABSTRACT FROM AUTHOR]

Sex chromosomes constantly exist in a dynamic state of evolution: rapid turnover and change of heterogametic sex during homomorphic state, and often stepping out to a heteromorphic state followed by chromosomal decaying. However, the forces driving these different trajectories of sex chromosome evolution are still unclear. The Japanese frog Glandirana rugosa is one taxon well suited to the study on these driving forces. The species has two different heteromorphic sex chromosome systems, XX‐XY and ZZ‐ZW, which are separated in different geographic populations. Both XX‐XY and ZZ‐ZW sex chromosomes are represented by chromosome 7 (2n = 26). Phylogenetically, these two systems arose via hybridization between two ancestral lineages of West Japan and East Japan populations, of which sex chromosomes are homomorphic in both sexes and to date have not yet been identified. Identification of the sex chromosomes will give us important insight into the mechanisms of sex chromosome evolution in this species. Here, we used a high‐throughput genomic approach to identify the homomorphic XX‐XY sex chromosomes in both ancestral populations. Sex‐linked DNA markers of West Japan were aligned to chromosome 1, whereas those of East Japan were aligned to chromosome 3. These results reveal that at least two turnovers across three different sex chromosomes 1, 3 and 7 occurred during evolution of this species. This finding raises the possibility that cohabitation of the two different sex chromosomes from ancestral lineages induced turnover to another new one in their hybrids, involving transition of heterogametic sex and evolution from homomorphy to heteromorphy. [ABSTRACT FROM AUTHOR]

Aim: Inulooligosaccharides in a Kampo formula, hochuekkito, have been shown to participate in the regulation of the pulmonary immune system. Difference in chain length distribution of the oligosaccharides strongly affects their immunopharmacological activities. This phenomenon cannot be explained by bifidogenic activity and/or short‐chain fatty acids produced by intestinal microflora from the oligosaccharides. Effects of intermediate‐size inulooligosaccharides, which have a similar chain length distribution as the oligosaccharides obtained from hochuekkito containing Atractylodis rhizoma, were analyzed on immunocompetent cells in Peyer's patches. Methods: Effect of intermediate‐size inulooligosaccharide preparation (degree of polymerization (d.p.) 3–15) on mRNA expression of genes of markers and functional molecules of stromal cells and type 3 innate lymphoid cells (ILC3) in Peyer's patches was analyzed. Results: Oral administration of intermediate‐size inulooligosaccharide preparation significantly up‐regulated expression of mRNAs of genes of not only marker molecules of fibroblastic reticular cells (FRC) and ILC3 but also immunological factors for positive and negative regulatory functions of FRC in addition to genes of auto‐immune regulator (AIRE), DEAF‐1 transcription factor, and some AIRE‐dependent tissue‐related antigens (TRA). Conclusion: FRC and ILC3 are suggested to be target cell candidates in Peyer's patches for inulooligosaccharides in hochuekkito formula containing Atractylodis rhizoma. [ABSTRACT FROM AUTHOR]

The recombinant N‐terminal domain of BC2L‐C lectin (rBC2LCN) is useful for detecting not only human pluripotent stem cells but also some cancers. However, the cancer types and stages that can be detected by rBC2LCN remain unclear. In this study, we identified the human breast carcinoma subtypes and stages that can be detected by rBC2LCN. Compared with rBC2LCN‐negative breast carcinoma cell lines, the rBC2LCN‐positive cells expressed higher levels of human epidermal growth factor receptor 2 (HER2) and epithelial marker genes. Importantly, rBC2LCN histochemical staining of human breast carcinoma tissues demonstrated the utility of rBC2LCN in detecting breast carcinoma types that express HER2 and have not spread much in the early phase of growth. We conclude that rBC2LCN may have potential as a detection probe and a drug delivery vehicle to identify and treat early‐stage HER2‐positive breast carcinoma. [ABSTRACT FROM AUTHOR]