Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 14 January 1972:
Vol. 175. no. 4018, pp. 134 - 140
DOI: 10.1126/science.175.4018.134
Prev | Table of Contents | Next

Articles

Gene Selection in Hemoglobin and in Antibody-Synthesizing Cells

David Kabat 1

1 University of Oregon Medical School, Portland 97201

Close linkage of mutually exclusive genes occurs in the non-agr chain hemoglobin genes and in the immunoglobulin genes of man and other mammals. The expression of one gene in the cluster precludes the expression of any other linked gene. A simple, testable theory of gene selection called "looping-out excision"which was designed only to explain this mutual exclusivity in the hemoglobin system is described. The theory is closely concordant with a wide range of previously unexplained findings concerning hematopoiesis— including the developmental changes of hemoglobins, the increases in immature or fetal forms of hemoglobin that accompany anemia, and with the distribution of adult and fetal hemoglobins among erythrocytes during normal embryogenesis and in various pathological conditions. One corollary of this theory is that erythroid tissue in the normal adult bone marrow is constantly recapitulating the developmental stages of its embryogenesis. Another corollary is that the selection from among the linked globin genes occurs independently on the two chromosomes of the diploid organism. Both of these corollaries are supported by the available data.

The same theory of gene selection is also remarkably consistent with known data for immunoglobulin synthesis; it could explain not only the mutually exclusive activation of linked variable genes but also the splicing which occurs between genetically linked variable and constant region genes for the immunoglobulin polypeptide chains. The agreement between these two different tissues is considered to be strong evidence that the proposed mechanism is correct at least in broad outline. Evidence from the genetics of maize and of drosophila also supports this theory of somatic tissue variegation. On the basis of these comparisons, I suggest that looping-out excision probably occurs also in other tissues and may be one means of gene selection and activation in differentiating cells.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Organization and Reorganization of Immunoglobulin Heavy-chain Genes.
T. Honjo, T. Kataoka, Y. Yaoita, A. Shimizu, N. Takahashi, Y. Yamawaki-Kataoka, T. Nikaido, S. Nakai, M. Obata, T. Kawakami, et al. (1981)
Cold Spring Harb Symp Quant Biol 45, 913-923
   Abstract »    PDF »
Stability of the individual globin genes during erythroid differentiation.
E Benz Jr, P Turner, J Barker, and A Nienhuis (1977)
Science 196, 1213-1214
   Abstract »    PDF »
Hemoglobin ontogenesis: test of the gene excision hypothesis.
T Papayannopoulou, P. Nute, G Stamatoyannopoulos, and T. McGuire (1977)
Science 196, 1215-1216
   Abstract »    PDF »
Somatic Changes in the Content and Context of Immunoglobulin Genes.
S. Tonegawa, N. Hozumi, G. Matthyssens, and R. Schuller (1977)
Cold Spring Harb Symp Quant Biol 41, 877-889
   Abstract »    PDF »
Hemoglobin Switching in Sheep and Goats: Occurrence of Hemoglobins A and C in the Same Red Cell.
A. W. Nienhuis and H. F. Bunn (1974)
Science 185, 946-948
   Abstract »    PDF »
Genetic Determination of Phenotypic Variation in Sickle Cell Trait.
W. E. Nance and J. Grove (1972)
Science 177, 716-718
   Abstract »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)