The α- and β-globin gene domains are a traditional model for study of the domain organization of the eucaryotic genome because these genes encode hemoglobin, a physiologically important protein. The α-globin and β-globin gene domains are organized in completely different ways, while the expression of globin genes is tightly coordinated, which makes it extremely interesting to study the origin of these genes and the evolution of their regulatory systems. In this review, the organization of the α- and β-globin gene domains and their genomic environment in different taxonomic groups are comparatively analyzed. A new hypothesis of possible evolutionary pathways for segregated α- and β-globin gene domains of warm-blooded animals is proposed.
In Danio rerio, the alpha- and beta-globin genes are present in two clusters: a major cluster located on chromosome 3 and a minor cluster located on chromosome 12. In contrast to the segregated alpha- and beta-globin gene domains of warm-blooded animals, in Danio rerio, each cluster contains both alpha- and beta-globin genes. Expression of globin genes present in the major cluster is controlled by an erythroid-specific enhancer similar to the major regulatory element of mammalian and avian alpha-globin gene domains. The enhancer controlling expression of the globin genes present in the minor locus has not been identified yet. Based on the distribution of epigenetic marks, we have selected two genomic regions that might harbor an enhancer of the minor locus. Using transient transfection of constructs with a reporter gene, we have demonstrated that a ~500-bp DNA fragment located ~1.7 Kb upstream of the αe4 gene possesses an erythroid-specific enhancer active with respect to promoters present in both the major and the minor globin gene loci of Danio rerio. The identified enhancer element harbors clustered binding sites for GATA-1, NF-E2, and EKLF similar to the enhancer of the major globin locus on chromosome 3. Both enhancers appear to have emerged as a result of independent evolution of a duplicated regulatory element present in an ancestral single alpha-/beta-globin locus that existed before teleost-specific genome duplication.
Using strand-specific reverse transcription followed by Real Time PCR analysis we have characterized the transcription profile of the segment of chicken α-globin gene domain harboring embryonic gene π, adult gene αD and spacer region separating these genes. It has been demonstrated that in erythroid cells of adult lineage the spacer region is transcribed in both directions. These results suggest a possibility that switching of α-globin genes expression is controlled by RNA-interference mechanism.
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