Triplication of a four-gene set during evolution of the goat β-globin locus produced three genes now expressed differentially during development

Abstract

Distinct hemoglobins are synthesized in goats at different stages of development, similar to humans. Embryonic hemoglobins (ζ2ε2 and α2ε2) are synthesized initially and are followed sequentially by fetal (α2β2(F)), preadult (α2β2(C)), and adult (α2β2(A)) hemoglobins. To help understand the basis of these switches, the genes of the β-globin locus have been cloned and their linkage arrangement has been determined by the isolation of λ phage carrying overlapping inserts of genomic goat DNA. The locus extends over 120 kilobase pairs and consists of 12 genes arranged in the following order: ε(I)-ε(II)-Ψβ(X)-β(C)-ε(III)-ε(IV)-Ψβ(Z)-β(A)-ε(V)-ε(VI)-Ψβ( Y)-β(F). Comparison of the nucleotide sequence of the 12 genes shows that the locus is organized into three homologous four-gene sets that presumably evolved by the triplication of an ancestral set of four genes (ε-ε-Ψβ-β). Interestingly, the three genes (β(C), β(A), and β(F)) located at the ends of the four-gene sets are expressed at different stages of development. Therefore, the goat β(F)-, β(C)-, and β(A)-globin genes appear to have evolved by a mechanism that includes the triplication of 40-50 kilobase pairs of DNA and the recruitment of newly formed genes for expression in fetal, preadult, and adult life.