MadSci Network: Biochemistry

Re: why does the mutation in Hemoglobin Yakima increase O2 binding affinity?

Date: Mon Oct 29 17:40:41 2007
Posted By: Neil Saunders, Computational biologist
Area of science: Biochemistry
ID: 1193426021.Bc

Dear questionner,

Thanks for your interesting question. Like you, I had some difficulty in finding out why oxygen affinity is higher in hemoglobin Yakima. First, I went to PubMed, the online database of scientific publications. My search there for "(hemoglobin OR haemoglobin) AND yakima" brought up only 10 papers, between 1967 and 1992. The same search at Google returns about 3 780 results.

One of those papers, Hemoglobin Yakina. I. Clinical and biochemical studies, (note the misspelling!) contains the following paragraph:

Of three possible structure-function relations which would account for the increased oxygen affinity of hemoglobin Yakima, only two seem likely. These are: (a) an intrachain shift in the normal relations between the F and G helices and the heme group, or (b) an effect of the substituted side chain at a region of contact between nonpolar residues of the alpha- and beta-chains which favors the oxyhemoglobin quarternary structure.

In other words - they are not sure themselves! However, what they suspect is that the mutation of Asp 99 to His results in a slight alteration to the structure of hemoglobin which makes the oxygen-bound form more energetically-favourable and so more likely to form. You can remind yourself about hemoglobin structure and how it influences function at this very good Wikipedia page.

I like your high-altitude theory, but I'm unable to find out if high-affinity hemoglobin mutations are actually more common in the Japanese, or indeed any other group of people who live at altitude. One study of native people in the Andes, Selective pressure has not acted against hypercoagulability alleles in high-altitude Amerindians, suggests that altitude is not a major selection pressure at least for some types of blood-related genes. You might like to submit this as a separate question in the Evolution or General Biology category.

I hope that helps with your question,

Jones RT, Osgood EE, Brimhall B, Koler RD.
Hemoglobin Yakina. I. Clinical and biochemical studies.
J Clin Invest. 1967 Nov;46(11):1840-7.

Rupert JL, Monsalve MV, Kidd KK, Tan C, Hochachka PW, Devine DV.
Selective pressure has not acted against hypercoagulability alleles in high-altitude Amerindians.
Ann Hum Genet. 2003 Sep;67(Pt 5):426-32.

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