I kind of have confusion between the first restriction endonuclease to be isolated and discovered. In class XII NCERT, it says that, "In the year 1963, the two enzymes responsible for restricting the growth of bacteriophage in Escherichia coli were discovered. One of these added methyl groups to the DNA, while the other cut DNA. The latter was called restriction endonuclease".

Now, "one of these added methyl groups to the DNA" refers to DNA methylase clearly and "the other cut DNA" must refer to EcoR1, I think?

In the next paragraph it is given that, "The first restriction endonuclease, Hind II, whose functioning depended on a specific DNA nucleotide sequence was isolated and characterised five years later".

What I understand from this is that, Hind II was the first restriction endonuclease to be discovered but EcoR1 the first to be isolated?

I went on many sites, but they all use these terms interchangeably.


1 Answer 1


The restriction endonuclease (RE) isolated from E. coli K strain was a type I restriction endonuclease, identified/characterized by Meselson and Yuan1 in 1968. Type I REs are site specific, but cleave DNA randomly.

The one isolated from Haemophilus influenzae by Smith and Wilcox2 in 1968 was the first type II RE and is now known by the name HindII - the isolate they had was actually a heterogenous mixture with HindIII, for which there are no sites in the one of the viruses they were digesting, so they were able to work out the specific site of digestion for HindII, but not HindIII. Type II REs are site specific and cleave at specific sites too, which makes them useful in molecular biology, as opposed to type I REs, which aren't so useful.

EcoRI (type II RE) wasn't isolated until 1971, and was done by Yoshimori as his PhD thesis at University of California, San Francisco (see reference 27 in Roberts; ref 3 below).

Roberts (2005) a succinct history of it all3. See sections on Restriction Enzymes and Polyacryamide Gel Electrophoresis for information about the discovery of type I and II REs respectively.


  1. Meselson M, Yuan R. DNA restriction enzyme from E. coli. Nature. 1968 Mar 23;217(5134):1110-4. doi: 10.1038/2171110a0. PMID: 4868368.

  2. Smith HO, Wilcox KW. A restriction enzyme from Hemophilus influenzae. I. Purification and general properties. J Mol Biol. 1970 Jul 28;51(2):379-91. doi: 10.1016/0022-2836(70)90149-x. PMID: 5312500.

  3. Roberts RJ. How restriction enzymes became the workhorses of molecular biology. Proc Natl Acad Sci U S A. 2005 Apr 26;102(17):5905-8. doi: 10.1073/pnas.0500923102. Epub 2005 Apr 19. PMID: 15840723; PMCID: PMC1087929.

  • $\begingroup$ So, EcoK I (?) is the RE referred to in the first paragraph and not EcoR I. On comparing Hind II and EcoR I, Hind II was the first to be isolated (1968), EcoR I being isolated only in 1971. Am I right? Man, my teacher got me hella confused. $\endgroup$
    – Meenakshi
    Jul 18, 2023 at 18:33
  • $\begingroup$ I could be EcoKI, but I don't know if this is actually the case; though a quick scan of the literature shows references to the Meselson paper, but whether this is related to KI itself??? I suggest you look through the literature and try looking up the history of EcoKI. $\endgroup$
    – bob1
    Jul 18, 2023 at 22:17

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