Role of a locus control region in the mutually exclusive expression of human red and green cone pigment genes
- Philip M. Smallwood*,†,
- Yanshu Wang*,†, and
- Jeremy Nathans*,†,‡,§,¶
- Departments of *Molecular Biology and Genetics, ‡Neuroscience, §Ophthalmology, and †Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD 21205
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Contributed by Jeremy Nathans
Abstract
Trichromacy in humans and other Old World primates evolved from a dichromatic color vision system ≈30–40 million years ago. One essential part of this evolution was the duplication and divergence of sequences on the X chromosome to create the present-day red and green cone pigment genes. Earlier work demonstrated that a locus control region (LCR) located upstream of these genes is essential for their expression. In the present work, we have generated a variety of modified human red and green pigment gene arrays that direct the expression of distinguishable histochemical reporters from each gene promoter. Transgenic mice carrying a single copy of each modified array were studied to define the role of three variables in producing mutually exclusive expression of red and green pigment transgenes: the distance between the promoter and the LCR, the identity of the visual pigment promoter, and LCR copy number. The results support a model in which the mutually exclusive expression of these genes in their respective cone types is controlled by competition between visual pigment promoters for pairing with the LCR, and they suggest a facile mechanism for the evolution of trichromacy after visual pigment gene duplication.
Footnotes
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↵ ¶ To whom reprint requests should be addressed at: 805 PCTB, 725 North Wolfe Street, Johns Hopkins University School of Medicine, Baltimore, MD 21205. E-mail: jnathans{at}jhmi.edu.
- Abbreviations:
- LCR,
- locus control region;
- ES cell,
- embryonic stem cell;
- AP,
- human placental alkaline phosphatase;
- PGK,
- phosphoglycerate kinase
- Copyright © 2002, The National Academy of Sciences
