318 R. M. JOHNSON ET AL. JOURNAL OF EXPERIMENTAL ZOOLOGY (MOL DEV EVOL) 288:318–326 (2000) © 2000 WILEY-LISS, INC. JEZ 2009 Humans and Old World Monkeys Have Similar Patterns of Fetal Globin Expression ROBERT M. JOHNSON, 1 * STEVEN BUCK, 1 CHI-HUA CHIU, 2 DOUGLAS A. GAGE, 3 TUN-LI SHEN, 3 ANDREW G. HENDRICKX, 4 DEBORAH L. GUMUCIO, 5 AND MORRIS GOODMAN 6 1 Department of Biochemistry & Molecular Biology, Wayne State Medical School, Detroit, Michigan 48201 2 Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06520 3 Mass Spectroscopy Facility, Department of Biochemistry, Michigan State University, East Lansing, Michigan 48824 4 California Regional Primate Research Center, University of California, Davis, California 45616 5 Department of Anatomy and Cell Biology, University of Michigan, Ann Arbor, Michigan 48109 6 Department of Anatomy and Cell Biology, Wayne State Medical School, Detroit, Michigan 48201 ABSTRACT The expression of ε- and γ-globin mRNA and protein has been determined in three Old World monkey species (Macaca mulatta, Macaca nemestrina, and Cercopithecus aethiops). Using RT-PCR with primers for ε- and γ-globin, both mRNAs were detected in early fetal stages, whereas at 128 days (85% of full term), only γ was expressed. High-performance liquid chromato- graphy was used for separation and quantitation, and matrix-assisted laser desorption/ionization mass spectrometry was used for identification of globin polypeptides. An α-globin polymorphism was observed in all of the species examined. During fetal life, γ-globin was the predominant ex- pressed β-type globin. The red blood cells of infants still contained substantial amounts of γ-globin, which declined to negligible levels in 14 weeks as β-globin expression reached adult values. The ratio of γ1- to γ 2-globins (equivalent to G γ/ A γ in humans) was approximately 2.5, similar to the G γ/ A γ ratio observed in humans. Thus, γ-globin gene expression in these Old World monkeys species has three features in common with human expression: expression of both duplicated γ genes, the rela- tive preponderance of γ1 over γ 2 expression, and the delay of the switch from γ- to β-globin until the perinatal period. Thus, the catarrhines seem to share a common pattern of developmental switching in the β-globin gene cluster, which is distinct from the timing of expression in either prosimians or the New World monkeys. Our results indicate that an Old World monkey, such as Rhesus, could serve as a model organism (resembling humans) for experimentally investigating globin gene expression patterns during the embryonic, fetal, and postnatal stages. J. Exp. Zool. (Mol. Dev. Evol.) 288:318–326, 2000. © 2000 Wiley-Liss, Inc. Grant sponsor: National Institutes of Health; Grant number: HL- 33940; Grant sponsor: National Science Foundation; Grant number: INT9602913; Grant sponsor: National Institutes of Health, National Center for Research Resources, Biotechnology Area; Grant number: RR-00480; Grant sponsor: National Institutes of Health; Grant num- ber: RR-00169. *Correspondence to: Robert M. Johnson, Department of Biochem- istry & Molecular Biology, Wayne State Medical School, 540 E. Canfield, Detroit, MI 48201. E-mail: rmjohns@med.wayne.edu Received 22 February 2000; Accepted 3 July 2000 All vertebrate hemoglobins are tetramers com- posed of two α-type and two β-type globin chains. In humans, a cluster of related genes on chromo- some 11 encodes the β-type globins: ε, G γ (or γ1), A γ (or γ 2), δ, and β. These genes are expressed at defined times during ontogeny. In humans (Bunn and Forget, ’86), the ε-globin gene is embryonic, expressed during the first 20% of gestation, after which it is down-regulated. The γ genes are up- regulated at this time and are expressed for the remaining 80% of prenatal development. After birth, γ gene expression declines as the adult δ- and β-globins become the predominant forms. The mechanism of the developmental switch from one globin gene to the next is of fundamental impor- tance for an understanding of stage-specific gene