Transcriptional reprogramming and backup between duplicate genes: is it a genomewide phenomenon?

Deleting a duplicate gene often results in a less severe phenotype than deleting a singleton gene, a phenomenon commonly attributed to functional compensation among duplicates. However, duplicate genes rapidly diverge in expression patterns after duplication, making functional compensation less probable for ancient duplicates. Case studies suggested that a gene may provide compensation by altering its expression upon removal of its duplicate copy. On the basis of this observation and a genomic analysis, it was recently proposed that transcriptional reprogramming and backup among duplicates is a genomewide phenomenon in the yeast Saccharomyces cerevisiae. Here we reanalyze the yeast data and show that the high dispensability of duplicate genes with low expression similarity is a consequence of expression similarity and gene dispensability, each being correlated with a third factor, the number of protein interactions per gene. There is little evidence supporting widespread functional compensation of divergently expressed duplicate genes by transcriptional reprogramming.