AUTHOR=Zhou Xiaoyan , Ning Yue , Xie Jingyi , Han Yi , Tang Chaonan , Su Caiyuan , Wan Qijuan , Wu Qisheng , Guo Xiang , Qi Jianfei , Ke Yizhou , Ge Hui , Cai Mingyi TITLE=Identification of sex-linked markers and genes in Portuguese oyster (Magallana angulata) JOURNAL=Frontiers in Marine Science VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/marine-science/articles/10.3389/fmars.2025.1542815 DOI=10.3389/fmars.2025.1542815 ISSN=2296-7745 ABSTRACT=The Portuguese oyster (Magallana angulata) is a valuable aquaculture species with sexual dimorphism in growth and nutritional traits, making it a promising candidate for sex-controlled breeding. However, the genetic mechanisms underlying its sex determination remain poorly understood. This study represents the first population-level investigation to identify sex-linked genetic markers and candidate genes in M. angulata using genome-wide association studies (GWAS) and transcriptomic analysis. A total of 1,613 sex-associated SNPs were identified, primarily located on Chr. 9 (7.99 Mb–10.51Mb). SNP annotation revealed 57 genes around these sex-associated SNPs. Transcriptomic analysis identified 8,635 differentially expressed genes (DEGs) between male and female gonads, of which 12 overlapped with GWAS-identified genes. Among these, four genes (5-HTR, ADPKD1-a, SCP, and SLC28A3) exhibited strong sex-specific genetic differentiation, with 5-HTR showing the most pronounced association. Further population genetic analysis revealed higher genetic diversity and heterozygosity of 5-HTR in males. Six sex-associated haplotypes based on SNPs within 5-HTR were constructed and validated in an independent population, although with reduced significance, suggesting both continuity and variation in sex determination mechanisms across populations. These findings provide a critical foundation for understanding the genetic basis of sex determination and advancing sex-controlled breeding strategies in M. angulata.