Mice divergently selected for high and low basal metabolic rates evolved different cell size and organ mass.

Evolution of metabolic rates of multicellular organisms is hypothesized to reflect the evolution of their cell architecture. This is likely to stem from a tight link between the sizes of cells and nuclei, which are expected to be inversely related to cell metabolism. Here, we analysed basal metabolic rate (BMR), internal organ masses and the cell/nucleus size in different tissues of laboratory mice divergently selected for high/low mass-corrected BMR and four random-bred mouse lines. Random-bred lines had intermediate levels of BMR as compared to low- and high-BMR lines. Yet, this pattern was only partly consistent with the between-line differences in cell/nucleus sizes. Erythrocytes and skin epithelium cells were smaller in the high-BMR line than in other lines, but the cells of low-BMR and random-bred mice were similar in size. On the other hand, the size of hepatocytes, kidney proximal tubule cells and duodenum enterocytes were larger in high-BMR mice than other lines. All cell and nucleus sizes were positively correlated, which supports the role of the nucleus in cell size regulation. Our results suggest that the evolution of high BMR involves a reduction in cell size in specialized tissues, whose functions are primarily dictated by surface-to-volume ratios, such as erythrocytes. High BMR may, however, also incur an increase in cell size in tissues with an intense transcription and translation, such as hepatocytes.