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We have isolated and sequenced a baboon apolipoprotein A-I (ApoA-I) clone from a liver cDNA library using a human cDNA hybridization probe. This baboon cDNA contains the entire ApoA-I coding region (801 bp, 267 aa), a 3' untranslated region, and a poly(A)tail. Among comparisons with apoAI sequences from other species, the baboon cDNA is most similar to that of the cynomolgus macaque (99.2% homologous) and least similar to the rat sequence (72.6% homologous). A high frequency of nonsynonymous substitutions are observed by alignment of baboon and human apoAI cDNAs, but comparisons of hydrophilicity profiles show that protein structure is conserved by substitutions of aa with similar properties. A polymorphic PstI cleavage site was identified by Southern blot analysis and subsequently mapped to the 5' end of the baboon apoAI gene. To identify effects of apoAI allelic variation on cholesterol metabolism, we used immunoblotting to compare the distributions of ApoA-I among lipoprotein size classes in baboons from each genotype under basal and atherogenic diets. We observed an increase of ApoA-I in high density lipoprotein (size class 1) particles after atherogenic diets in homozygotes for one allele, as compared to slight decreases in the other genotypes.

We have constructed a cDNA library from baboon ventricle and have used a rabbit beta-myosin heavy chain (beta-MHC) cDNA probe to isolate cross-hybridizing clones. The nucleotide sequence of one such clone, lambda BMHC beta 14, contains a portion of the coding region of the light meromyosin (LMM) region and the 3'-untranslated region of the baboon ventricular MHC. This cDNA clone is identified as containing beta-MHC sequences on the basis of similarity with the 3'-untranslated regions of beta-MHC genes from man (96% homologous) and rat (71% homologous), and dissimilarity with the 3'-untranslated region of the rat alpha-MHC gene (25% homologous). Alignment and comparison of the baboon cDNA nucleotide sequence with a human cDNA sequence reveal two amino acid substitutions in the LMM region that cause differences in their hydrophilicity profiles. These differences may alter MHC functions such as filament assembly. We have used baboon beta-MHC cDNA clones to construct probes for S1 nuclease protection studies to detect and to distinguish cardiac MHC gene transcripts in baboon ventricle, atrium, and diaphragm. As in human tissues, beta-MHC gene transcripts are detected in RNA from baboon ventricle and diaphragm. In baboon atrium, we detect beta-MHC gene transcripts as well as transcripts that may represent expression of the alpha-MHC gene. This study represents the first examination of cardiac MHC genes and gene expression in tissues from a large mammal that is closely related to man.