Metabolome Diversity Enhances Resistance of Intertidal Clams to Thermal Stress

Global warming and marine heatwaves have devastating impacts on marine ectotherms. Clams inhabiting sandflats are frequently exposed to air and high temperatures. Different geographical species/populations facing diverse thermal environments may exhibit divergent physiological capabilities to cope with local conditions, and understanding species/population-specific physiological plasticity has been highlighted as important to fully uncover species' tolerance capacity within the highly heterogeneous spatial patterns. In the present study, we conducted metabolomic analyses of four Meretrix populations along China's coast, including three populations of Meretrix petechialis and one of Meretrix lusoria, to illustrate species/population-specific metabolomic responses to thermal stress. Our results indicated that the thermal environments of clam habitats varied along the coastlines. Metabolome responses showed species/population-specific patterns in response to high temperatures, suggesting metabolomic plasticity among species/populations. The northern populations mainly respond to high-temperature stress by enhancing antioxidant defenses and adjusting energy metabolism. Glycerophospholipid metabolism was a vital metabolic response to thermal stress in the southern species/population. GDP-L-fucose levels were positively correlated with the clams' upper thermal limits. Additionally, metabolite-based genome-wide association studies on GDP-L-fucose identified six candidate genes: neuropeptide FF receptor 2-like, E3 ubiquitin-protein ligase rnf213-alpha-like isoform X2, uncharacterized protein LOC123550816, solute carrier family 28 member 3-like isoform X1, adenylate kinase isoenzyme 5-like isoform X6, and E3 ubiquitin-protein ligase TRIM33-like, highlighting the potential roles of codon usage bias and changes in protein structure. Overall, we emphasized metabolome diversity across species/populations and stressed the importance of accounting for it when assessing the impacts of climate change on marine ectotherms.