The name derives from the 2 rounds of duplication originally hypothesized by Ohno, but refined in a 1994 version, and the term 2R hypothesis was probably coined in 1999.
[4] Ohno presented the first version of the 2R hypothesis as part of his larger argument for the general importance of gene duplication in evolution.
Based on relative genome sizes and isozyme analysis, he suggested that ancestral fish or amphibians had undergone at least one and possibly more cases of "tetraploid evolution".
[7] (Furthermore, much later molecular phylogenetics has shown that vertebrates are more closely related to tunicates than to lancelets, thus negating the logic of this analysis.
[7] Taken together, these two lines of evidence suggest that two genome duplications occurred in the ancestry of vertebrates, after it had diverged from the cephalochordate evolutionary lineage.
[18][19] When complete genome sequences became available for vertebrates, Ciona intestinalis and lancelets, it was found that much of the human genome was arranged in paralogy regions that could be traced to large-scale duplications,[20] and that these duplications occurred after vertebrates had diverged from tunicates[11] and lancelets.
The controversy raging in the late 1990s was summarized in a 2001 review of the subject by Wojciech Makałowski, who stated that "the hypothesis of whole genome duplications in the early stages of vertebrate evolution has as many adherents as opponents".