The structure and evolution of the human β-globin gene family

We present the results of a detailed comparison of the primary structure of human β-like globin genes and their flanking sequences. Among the sequences located 5′ to these genes are two highly conserved regions which include the sequences ATA and CCAAT located 31 ± 1 and 77 ± 10 bp, respectively, 5′ to the mRNA capping site. Similar sequences are found in the corresponding locations in most other eucaryotic structural genes. Calculation of the divergence times of individual β-like globin gene pairs provides the first description of the evolutionary relationships within a gene family based entirely on direct nucleotide sequence comparisons. In addition, the evolutionary relationship of the embryonic β-globin gene to the other human β-like globin genes is defined for the first time. Finally, we describe a model for the involvement of short direct repeat sequences in the generation of deletions in the noncoding and coding regions of β-like globin genes during evolution.