Comparative Transcriptomics Reveal Key Genes and Pathways Driving the Diversity of Heritable Inner Shell Nacre Colors in the Freshwater Pearl Mussel (Sinohyriopsis cumingii, Lea 1852)

Pearl color is the primary determinant of its value, and the mantle donor tissue (saibo) used in pearl culture plays a critical role in color formation. To elucidate the molecular mechanisms underlying nacre color, we performed comparative transcriptomic analyses of saibo tissues from <i>Sinohyriopsis cumingii</i> displaying three representative phenotypes: white (W), purple (P), and golden (G). A total of 364 differentially expressed genes (DEGs) (102 upregulated and 162 downregulated genes) were identified in W vs. P. A total of 770 DEGs (467 upregulated and 303 downregulated genes) were identified in W vs. G. KEGG pathway analysis revealed significant differences in the expression of genes mainly involved in pigment-based and structural coloration, including amino sugar and nucleotide sugar metabolism (ko00520), cell adhesion molecules (ko04514), tyrosine metabolism (ko00350), ECM-receptor interaction (ko04512), and PI3K-Akt signaling pathway (ko04151). Subsequent integrative analyses across W vs. P and W vs. G groups identified 45 key regulatory genes, which were classified into four functional categories: extracellular matrix protein synthesis and biomineralization (e.g., <i>chit</i>, <i>silkmaxin</i>, <i>bmp2/7</i>, <i>profilin</i>, <i>perlucin2</i>), organic pigment metabolism (e.g., <i>tyr</i>, <i>typ</i>, <i>dbh</i>, <i>bco2</i>, <i>gst5</i>, <i>ldlr</i>, <i>cpox</i>, <i>pks-like 1</i>, <i>pks15</i>), metal ion metabolism and accumulation (e.g., <i>hip-like</i>, <i>fcr1</i>, <i>ferritin 2</i>), and epigenetic regulation (e.g., <i>metK</i>, <i>mbd4/6</i>, <i>mettl24/27</i>, <i>alkbh6</i>). Taken together, our findings reaffirm the complex nature of pearl coloration and reveal that structural coloration, pigment biosynthesis, and epigenetic modulation collectively shape nacre color formation, which paves the way for further functional elucidation of color-related genes and facilitates selective breeding practices in <i>S. cumingii</i>.