Fig. 2: Sirenian-specific changes in iodine uptake and organification genes.

a Schematic diagram showing iodine uptake by a dugong, from seagrass ingestion to fermentation in the hindgut and reduction of iodine to iodide (I-), to iodide transport in the bloodstream to the thyroid. The thyroid is an endocrine gland consisting of follicles, structural units of epithelial cells enclosing a lumen (the colloid) harboring thyroglobulin (TG). TG is a precursor for thyroid hormones (indicated by T3 and T4) biogenesis and is also an iodide storage and carrier protein. b Iodide is transported from the bloodstream to thyroid follicular cells by NIS (encoded by SLC5A5) interacting with KCNQ1 and KCNE2. Genes with sirenian-specific amino acid substitutions in orange and genes rapidly evolving and positively selected in sirenians in blue and red, respectively. c Alignment showing an amino acid substitution in transmembrane domains of sirenian SLC5A5 (NIS). Sirenian-specific residues shown in red shading. Red boxes indicate residues shown to be important for NIS function19,20,21,22. d Alignment showing amino acid substitution in the ISK_Channel domain of sirenian KCNE2. Sirenian-specific residues shown in red shading. e Radioiodide uptake rates of human and sirenian SLC5A5 (NIS) constructs in HEK293T cells. The expression constructs human2dugong and dugong2human code for NIS proteins where the five sirenian-specific amino acids in (c) were replaced by their corresponding counterparts. The bar graph y-axis shows the percent of Na125I uptake. Data derived from five independent experiments with single measurements (three for human2dugong), presented as mean ± S.D. relative to the control (empty pcDNA3.1 vector), while dots represent individual data points per experiment (****P < 0.0001, ***P < 0.001, **P < 0.01, *P < 0.05, one-sided ANOVA with Tukey’s multiple comparisons test). The exact P values compared to the control from left to right are 1.47 × 10−3, 0, 0, 1.50 × 10−6, and 1.90 × 10−4; human compared to human2dugong, 0.015; and dugong compared to dugong2human, 1.00 × 10−7. A P value of 0 indicates a number below 2.22 × 10−16.