2R hypothesis

The 2R hypothesis or Ohno's hypothesis, first proposed by Susumu Ohno in 1970, is a hypothesis in genomics and molecular evolution suggesting that the genomes of the early vertebrate lineage underwent two complete genome duplications, and thus modern vertebrate genomes reflect paleopolyploidy. 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. Variations in the number and timings of genome duplications typically still are referred to as examples of the 2R hypothesis. The 2R hypothesis has been the subject of much research and controversy; however, with growing support from genome data, including the human genome, the balance of opinion has shifted strongly in favour of support for the hypothesis. According to Hokamp et al. (2003), the version of the genome duplication hypothesis from which 2R hypothesis takes its name appears in Holland et al. (1994) and the term was coined in Hughes (1999).

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". He later added to this argument the evidence that most paralogous genes in vertebrates do not demonstrate genetic linkage. Ohno argued that linkage should be expected in the case of individual tandem duplications (in which a duplicate gene is added adjacent to the original gene on the same chromosome), but not in the case of chromosome duplications.

In 1977, Schmidtke and colleagues showed that isozyme complexity is similar in amphioxus and tunicates, contradicting a prediction of Ohno's hypothesis that genome duplication occurred in the common ancestor of amphioxus and vertebrates. However, this analysis did not examine vertebrates, so could say nothing about later duplication events. (Furthermore, much later molecular phylogenetics has shown that vertebrates are more closely related to tunicates than to amphioxus, thus negating the logic of this analysis.) The 2R hypothesis saw a resurgence of interest in the 1990s for two reasons. First, gene mapping data in humans and mice revealed extensive paralogy regions - sets of genes on one chromosome related to sets of genes on another chromosome in the same species, indicative of duplication events in evolution. Paralogy regions were generally in sets of four. Second, cloning of Hox genes in amphioxus revealed presence of a single Hox gene cluster, in contrast to the four clusters in humans and mice. Data from additional gene families revealed a common one-to-many rule when amphioxus and vertebrate genes were compared. 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.

...
Wikipedia