The golden pompano (Trachinotus ovatus) is a marine fish species in the family Carangidae. We constructed a chromosome-level genome assembly of a male golden pompano. QTL-mapping and GWAS analysis showed that this species has a ZZ/ZW sex determination system and a sex defining SNP (Chr16:18219150:G/A), located on the splice donor site (GT-AG) of the first intron of Hsd17b1, was exclusively associated with the phenotypic sex. The W-linked coding sequences of Hsd17b1 were conserved across vertebrates, while Z-linked coding sequences introduced extra 64 bases and were malfunctional. The golden pompano and the greater amberjack (Seriola dumerili), divergent in 57 million years ago in the same family, share the same features of sex determination, including the same sex determining gene, malfunctional Z-linked haplotypes, undifferentiated sex chromosomes except that the sex defining SNPs are different. In simulation analysis, turnover of sex determining mutation, single mutation dominating sex determination and undifferentiated sex chromosomes were also observed. We proposed a hypothesis that W-linked haplotypes of the sex determining gene of Hsd17b1 were under purifying selection, Z-linked haplotypes may evolve near neutrally, recurrent and directional transformations from W-linked haplotypes to Z-linked haplotypes caused by inactivating mutations, relatively strong forces of drift and recombination comprehensively contributed to turnover of sex defining mutation and undifferentiation of sex chromosome. We also established zebrafish mutants and homozygous mutants were “all male”, which indirectly supported this hypothesis.

No abstract

No abstract

Backgrounds: Lung adenocarcinoma is one of the most common malignant tumors, in which KEAP1-NFE2L2 pathway is altered frequently. The biological features and intrinsic heterogeneities of KEAP1/NFE2L2-mutant lung adenocarcinoma remain unclear. Methods: Multiplatform data from The Cancer Genome Atlas (TCGA) were adopted to identify two subtypes of lung adenocarcinoma harboring KEAP1/NFE2L2 mutations. Bioinformatics analyses, regarding immune microenvironment, methylation level and mutational signature, were performed to characterize intrinsic heterogeneities. Meanwhile, initial results were also validated by using common lung adenocarcinoma cell lines, which revealed consistent features of KEAP1/NFE2L2-mutant subtypes. Furthermore, cell line samples were adopted for drug sensitivity screening based on public datasets. Results: Two mutant subtypes (P1 and P2) of patients were identified in TCGA. P2 patients had significantly heavier smoking levels and worse survival compared with P1 patients. The P2 subset was characterized by active immune microenvironment and more smoking-induced genomic alterations, including methylation and somatic mutations. Validations of the corresponding features in mutant cell lines were achieved to some degrees. Several compounds which were sensitive to mutant subtype of lung adenocarcinoma were identified, such as inhibitors of PI3K/Akt and IGF1R signaling pathways. Conclusions: KEAP1/NFE2L2 mutant lung adenocarcinoma showed potential heterogeneities. The intrinsic heterogeneities of KEAP1/NFE2L2 were associated with immune microenvironment and smoking-related genomic aberrations.