Somatic polyploidy supports biosynthesis and tissue function by increasing transcriptional output.

Cell size and biosynthetic capacity generally increase with increased DNA content. Somatic polyploidy has therefore been proposed to be an adaptive strategy to increase cell size in specialized tissues with high biosynthetic demands. However, if and how DNA concentration limits cellular biosynthesis in vivo is not well understood. Here, we show that polyploidy in the Caenorhabditis elegans intestine is critical for cell growth and yolk biosynthesis, a central role of this organ. Artificially lowering the DNA/cytoplasm ratio by reducing polyploidization in the intestine gave rise to smaller cells with dilute mRNA. Highly expressed transcripts were more sensitive to this mRNA dilution, whereas lowly expressed genes were partially compensated-in part by loading more RNA Polymerase II on the remaining genomes. Polyploidy-deficient animals produced fewer and slower-growing offspring, consistent with reduced synthesis of highly expressed yolk proteins. DNA-dilute cells had normal total protein concentration, which we propose is achieved by increasing the expression of translational machinery at the expense of specialized, cell-type-specific proteins.