The structure and transcription of four linked rabbit beta-like globin genes

Abstract

Rabbit chromosomal DNA contains a cluster of four linked beta-like globin genes arranged in the orientation 5'-beta 4-(8kb)-beta 3-(5 kb)-beta 2-(7-kb)-beta 1-3'. Determination of the nucleotide sequence of gene beta 1 confirms that this gene corresponds to the second type of two common co-dominant alleles encoding the adult beta-globin chain. With the exception of two nucleotide substitutions in the large intervening sequence (intron), the intron and flanking sequences are identical with the nucleotide sequence of the first type determined by Weissmann et al. (1979). A 14S polyadenylated transcript containing large intron sequences (possibly a mRNA precursor) is detected in the bone marrow cells of anemic rabbits. Gene beta 2 has limited sequence homology to adult and embryonic beta-globin probes and lacks a detectable mRNA transcript in the erythropoietic tissues examined. It contains at least one intervening sequence analogous to the large intron in gene beta 1. Genes beta 3 and beta 4 both contain an intron of 0.8 kb. Partial DNA sequence analysis indicates that the large intron in beta 4 is located between codons for amino acids lysine and leucine in an analogous position to that of the large intron in beta 1. In addition, a second smaller intron interrupts the 5' coding sequences of gene beta 4. Both genes beta 3 and beta 4 are transcribed in embryonic globin-producing cells. Their DNA sequence homology is limited, however, to a segment of approximately 0.2 kb located on the 5' side of the large intron.