Editing Genetic linkage (section)

===Linkage of genetic sites within a gene===

In the early 1950s the prevailing view was that the genes in a [[chromosome]] are discrete entities, indivisible by [[genetic recombination]] and arranged like beads on a string.  During 1955 to 1959, Benzer performed [[genetic recombination]] experiments using [[T4 rII system|rII]] mutants of [[Escherichia virus T4|bacteriophage T4]].  He found that, on the basis of recombination tests, the sites of [[mutation]] could be mapped in a linear order.<ref>Benzer S. Fine structure of a genetic region in bacteriophage.  Proc Natl Acad Sci U S A. 1955;41(6):344-354. doi:10.1073/pnas.41.6.344</ref><ref>Benzer S. On the topology of the genetic fine structure. Proc Natl Acad Sci U S A. 1959;45(11):1607-1620. doi:10.1073/pnas.45.11.1607</ref> This result provided evidence for the key idea that the gene has a linear structure equivalent to a length of [[DNA]] with many sites that can independently mutate.{{cn|date=December 2024}}

Edgar et al.<ref>{{cite journal | pmc=1210321 | date=1962 | last1=Edgar | first1=R. S. | last2=Feynman | first2=R. P. | last3=Klein | first3=S. | last4=Lielausis | first4=I. | last5=Steinberg | first5=C. M. | title=Mapping Experiments with R Mutants of Bacteriophage T4d | journal=Genetics | volume=47 | issue=2 | pages=179–186 | doi=10.1093/genetics/47.2.179 | pmid=13889186 }}</ref> performed mapping experiments with r mutants of bacteriophage T4 showing that recombination frequencies between rII mutants are not strictly additive. The recombination frequency from a cross of two rII mutants (a x d) is usually less than the sum of recombination frequencies for adjacent internal sub-intervals (a x b) + (b x c) + (c x d). Although not strictly additive, a systematic relationship was observed<ref>{{cite journal | pmc=1210971 | date=1965 | last1=Fisher | first1=K. M. | last2=Bernstein | first2=H. | title=The Additivity of Intervals in the rIIA Cistron of Phage T4d | journal=Genetics | volume=52 | issue=6 | pages=1127–1136 | doi=10.1093/genetics/52.6.1127 | pmid=5882191 }}</ref> that likely reflects the underlying molecular mechanism of [[genetic recombination]].