The evolutionary position of subfunctionalization, downgraded.

Current data from complete eukaryotic genomes indicate that ancestral gene duplications, followed by a mutational process called fractionation, generated profound and orderly changes in gene content. Most of these duplicated genes are removed. At least three hypotheses may explain the exceptional genes retained post-duplication: (1) Gain-of-Function; (2) Subfunctionalization, and (3) Balanced Gene Drive. Each is evaluated as an explanation for gene content data. Subfunctionalization, the most popular explanation, predicts no relationship at all between gene function and post-duplicate retention, and if there were particular sorts of 'subfunctionalizable' genes, these should be over-retained following any sort of duplication. Duplications may be local, segmental or whole genome. Gene content data from three plant genomes, reflecting three independent tetraploidies and many tandem duplications, are not explained by Subfunctionalization. Specifically, genes encoding transcription factors and ribosomal components are significantly over-retained following tetraploidy and under-retained among local duplicates. In addition, transcription factor families in Arabidopsis show a reciprocal relationship when retention is monitored after local duplication versus after tetraploidy; only Balanced Gene Drive predicts reciprocity. Vertebrates also retain genes nonrandomly following tetraploidies, but the data are preliminary. Removing subfunctionalization as the duplicate retention mechanism is of high theoretical importance. It clears the way for 'Mutationist' hypotheses that may help explain baffling adaptations and trends in eukaryotic evolution that have been largely ignored. This essay recognizes the potential evolutionary importance of saltatory chromosomal events that may change gene content - expand gene families - independent of allelic diversity.