Weak 5′-mRNA Secondary Structures in Short Eukaryotic Genes

Experimental studies of translation have found that short genes tend to exhibit greater densities of ribosomes than long genes in eukaryotic species. It remains an open question whether the elevated ribosome density on short genes is due to faster initiation or slower elongation dynamics. Here, we address this question computationally using 5′-mRNA folding energy as a proxy for translation initiation rates and codon bias as a proxy for elongation rates. We report a significant trend toward reduced 5′-secondary structure in shorter coding sequences, suggesting that short genes initiate faster during translation. We also find a trend toward higher 5′-codon bias in short genes, suggesting that short genes elongate faster than long genes. Both of these trends hold across a diverse set of eukaryotic taxa. Thus, the elevated ribosome density on short eukaryotic genes is likely caused by differential rates of initiation, rather than differential rates of elongation.