The 2R hypothesis or Ohno's hypothesis, first proposed by Susumu Ohno

Susumu Ohno

was an Asian American geneticist and evolutionary biologist, and seminal researcher in the field of molecular evolution.- Biography :Susumu Ohno was born of Japanese parents in Seoul, Korea, on February 1, 1928. The second of five children, he was the son of the minister of education of the...

 in 1970, is a contested hypothesis in genomics

Genomics

Genomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...

 and molecular evolution

Molecular evolution

Molecular evolution is in part a process of evolution at the scale of DNA, RNA, and proteins. Molecular evolution emerged as a scientific field in the 1960s as researchers from molecular biology, evolutionary biology and population genetics sought to understand recent discoveries on the structure...

 suggesting that the genomes of the early vertebrate

Vertebrate

Vertebrates are animals that are members of the subphylum Vertebrata . Vertebrates are the largest group of chordates, with currently about 58,000 species described. Vertebrates include the jawless fishes, bony fishes, sharks and rays, amphibians, reptiles, mammals, and birds...

 lineage underwent one or more complete genome duplications, and thus modern vertebrate genomes reflect paleopolyploidy

Paleopolyploidy

Paleopolyploidy refers to ancient genome duplications which occurred at least several million years ago . The genome doubling event could either be an autopolyploidy or an allopolyploidy. Due to functional redundancy, genes are rapidly silenced and/or lost from the duplicated genomes...

. The name derives from the 2 rounds of duplication hypothesized by a 1994 version, and the term 2R hypothesis was probably coined in 1999; variations in the number of duplications typically still are referred to as examples of the 2R hypothesis. Since Ohno proposed the first version of it in Evolution by Gene Duplication, the 2R hypothesis has been the subject of much research, but even with recent data from the human genome

Human genome

The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...

, it remains a matter of scientific dispute.

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's argument

Ohno presented the first version of the 2R hypothesis as part of his larger argument for the general importance of gene duplication

Gene duplication

Gene duplication is any duplication of a region of DNA that contains a gene; it may occur as an error in homologous recombination, a retrotransposition event, or duplication of an entire chromosome.The second copy of the gene is often free from selective pressure — that is, mutations of it have no...

 in evolution

Evolution

Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

. Based on relative genome sizes, 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

Genetic linkage

Genetic linkage is the tendency of certain loci or alleles to be inherited together. Genetic loci that are physically close to one another on the same chromosome tend to stay together during meiosis, and are thus genetically linked.-Background:...

. 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.

Later evidence

The 2R hypothesis saw a resurgence of interest in the 1990s, with multiple suggestions for the time and number of duplications. Estimates for the dates of duplication events range from before 640 million years ago to after 450 million years ago. One argument for the hypothesis relies on the number of genes in mammals, which was previously estimated at around four times the number in invertebrate genomes (though more recent estimates are less than half that). Some analyses of gene families in human chromosomes have shown patterns that are not consistent with the 2R hypothesis. Parsimony analysis has produced some results that, while not supportive of the hypothesis, do not rule it out. According to a 2001 review of the subject by Wojciech Makałowski, "the hypothesis of whole genome duplications in the early stages of vertebrate evolution has as many adherents as opponents"; Makałowski argues that the overall balance of current evidence seems to be against it, but that it is not easily falsifiable because it can be modified to accommodate a wide range of data. Others analyzing duplications in the draft human genome sequence have claimed that genome data provides evidence of "extensive duplication" and that the parsimony tests that cast doubt on the hypothesis are of questionable validity. A review in 2007 by Masanori Kasahara states that there is now "incontrovertible evidence supporting the 2R hypothesis" and that "a long-standing debate on the 2R hypothesis is approaching the end".