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Selection for short introns in highly expressed genes

Abstract

Transcription is a slow and expensive process: in eukaryotes, approximately 20 nucleotides can be transcribed per second1,2 at the expense of at least two ATP molecules per nucleotide3. Thus, at least for highly expressed genes, transcription of long introns, which are particularly common in mammals, is costly. Using data on the expression of genes that encode proteins in Caenorhabditis elegans and Homo sapiens, we show that introns in highly expressed genes are substantially shorter than those in genes that are expressed at low levels. This difference is greater in humans, such that introns are, on average, 14 times shorter in highly expressed genes than in genes with low expression, whereas in C. elegans the difference in intron length is only twofold. In contrast, the density of introns in a gene does not strongly depend on the level of gene expression. Thus, natural selection appears to favor short introns in highly expressed genes to minimize the cost of transcription and other molecular processes, such as splicing.

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Figure 1: Scatter plots of the average intron length in a gene versus gene expression.
Figure 2: Comparison of average intron lengths and total exon lengths in genes with high and low expression.

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Acknowledgements

We are grateful to A. Kondrashov, I. Rogozin and A. Feldman for reading the manuscript and P. Bouman, J. Cherry, J. Blumensteil and T. Kim for discussion.

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Correspondence to Fyodor A. Kondrashov.

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Castillo-Davis, C., Mekhedov, S., Hartl, D. et al. Selection for short introns in highly expressed genes. Nat Genet 31, 415–418 (2002). https://doi.org/10.1038/ng940

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