Mammalian Genes Preferentially Co-Retained in Radiation Hybrid Panels Tend to Avoid Coexpression

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.

共表达（Coexpression）被广泛应用于探究真核基因组中功能相关基因的功能模块。然而，本研究发现，通过辐射杂交（radiation hybrid, RH）基因型鉴定得到的哺乳动物遗传互作基因，往往在不同组织中未呈现共表达特征。在控制染色体连锁、染色体间距、基因重复等潜在混杂因素后，该模式仍保持稳定。由于超过99.9%的遗传互作基因是基于更高的共保留频率（co-retention frequencies）鉴定得到的，本研究结果表明，共表达未必能作为基因组中两个基因需要共同存在的依据——而这一条件正是其编码蛋白在细胞内实现协同功能的前提。因此，在探究基因组内基因的功能相关性时，需谨慎使用共表达信息。