Mammalian genes preferentially co-retained in radiation hybrid panels tend to avoid coexpression

Abstract

Coexpression has been frequently used to explore modules of functionally related genes in eukaryotic genomes. However, we found that genetically interacting mammalian genes identified through radiation hybrid (RH) genotypes tend not to be coexpressed across tissues. This pattern remained unchanged after controlling for potential confounding factors, including chromosomal linkage, chromosomal distance, and gene duplication. Because >99.9% of the genetically interacting genes were identified according to the higher co-retention frequencies, our observation implies that coexpression is not necessarily an indication of the need for the co-presence of two genes in the genome, which is a prerequisite for cofunctionality of their coding proteins in the cell. Therefore, coexpression information must be applied cautiously to the exploration of the functional relatedness of genes in a genome.

Figure 1. Coexpression in and characteristics of chromosomal linkage of CRGPs vs. nCRGPs.

Box plots of ln[(1+CoExp)/(1−CoExp)] of CRGPs vs. nCRGPs in (A) all gene pairs, (C) unlinked gene pairs, and (D) linked gene pairs with specified ranges of D. CoExp is measured by Spearman's ρ of expression levels between genes across human tissues (see Fig. S2 for CoExp measured by Pearson's r). (B) Box plots of logD of linked CRGP vs. linked nCRGPs. Upper quartile, median, and lower quartile values are indicated in each box. Bars outside the box indicate semi-quartile ranges. P-values are from a Mann-Whitney U test.

Figure 2. nCRGPs comprise a higher percentage of highly coexpressed genes.

Compared with nCRGPs, CRGPs have a lower percentage of gene pairs with high coexpression, as defined by the threshold of CoExp shown in the bottom, after controlling for chromosomal linkage. CoExp is measured by Spearman's ρ of expression levels between genes (see Fig. S6 when CoExp was measured by Pearson's r). Error bars show one standard error of the proportion. P-values are from a χ² test.