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Human dihydrofolate reductase gene organization: Extensive conservation of the G + C-rich 5′ non-coding sequence and strong intron size divergence from homologous mammalian genes

Yang, Jiyoung K. and Masters, Jeffrey N. and Attardi, Giuseppe (1984) Human dihydrofolate reductase gene organization: Extensive conservation of the G + C-rich 5′ non-coding sequence and strong intron size divergence from homologous mammalian genes. Journal of Molecular Biology, 176 (2). pp. 169-187. ISSN 0022-2836. https://resolver.caltech.edu/CaltechAUTHORS:20190501-163158640

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Abstract

The complete human dihydrofolate reductase (DHFR) gene has been cloned from four recombinant lambda libraries constructed with the DNA from a methotrexate-resistant human cell line with amplified DHFR genes. The detailed organization of the gene has been determined by restriction mapping of the cloned fragments and DNA sequencing of all the protein coding regions and adjacent intron segments, and shown to correspond to that of the native human DHFR gene. The gene spans a length of approximately 29 × 103 bases from the ATG initiator codon to the end of the 3′ untranslated region, and contains five introns that interrupt the protein coding sequence. The number and positions of introns are identical to those found in the mouse gene. By contrast, the size of the homologous introns (with the exception of the first one) varies greatly, up to several fold, in the genes from man, mouse and Chinese hamster; the intron sequences also exhibit a great divergence, except in the junction regions. A striking sequence homology, extending over several hundred nucleotides, exists between the human and mouse gene 5′ non-coding regions. These regions are characterized by an unusually high G + C content, 72% and 66% in the human and mouse genes, respectively, which is maintained in the first coding segment and first intron, and is in sharp contrast to the relatively low G + C content (~40%) of the remainder of the gene.


Item Type:Article
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https://doi.org/10.1016/0022-2836(84)90419-4DOIArticle
Additional Information:© 1984 Published by Elsevier. Received 12 December 1983, Revised 3 February 1984. These investigations were supported by National Institutes of Health grants (GM11766 and T32 GM07616. We are very grateful to Dr A. Chomyn for carrying out the chromosome preparation and fractionation. B. Maurer for carrying out, some of the genomic blot hybridizations, Dr. F. Almalric (Centre de Recherche de Biochimie et de Génetique Cellulaires du C.N.R.S., Toulouse, France) for help in some of the early mapping studies and valuable discussions, Dr J. Mullins (Department of Microbiology. Harvard University) for providing the phage λJ1, Dr T. O. Baldwin (Texas A & M University, College Station. Texas) for providing the strain TB1, and T. Hunkapiller and Dr L. Hood for help in the computer program analysis of the data and for making the best-fit plotting program available to us prior to publication. The excellent assistance of Ms Doris Finch and Ms Arger Drew is gratefully acknowledged.
Funders:
Funding AgencyGrant Number
NIHGM11726
NIH Predoctoral FellowshipT32 GM07616
Issue or Number:2
Record Number:CaltechAUTHORS:20190501-163158640
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190501-163158640
Official Citation:Jiyoung K. Yang, Jeffrey N. Masters, Giuseppe Attardi, Human dihydrofolate reductase gene organization: Extensive conservation of the G + C-rich 5′ non-coding sequence and strong intron size divergence from homologous mammalian genes, Journal of Molecular Biology, Volume 176, Issue 2, 1984, Pages 169-187, ISSN 0022-2836, https://doi.org/10.1016/0022-2836(84)90419-4. (http://www.sciencedirect.com/science/article/pii/0022283684904194)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:95160
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:02 May 2019 15:22
Last Modified:03 Oct 2019 21:10

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