Structural and functional analysis of the goat epsilon-globin genes

Abstract

Since none of the vertebrate β-globin loci studied to date has more than two functional embryonic β-like globin genes, it would be unique if all six goat embryonic β-globin genes were required for its survival. In this study we have asked whether all six embryonic genes in the goat are functional. This question has been addressed by examining the transient expression of these genes in HeLa cells and correlating these results with the sequence information obtained to date. Our studies show that only ε I and ε II are functional while the remaining four ε-globin genes are nonfunctional i.e., pseudogenes. Interestingly, the two active ε-globin genes are located at the 5' end of the locus. While this unusual inactivation pattern may be the result of chance, it could also have resulted because the two duplication events, of the ancestral gene set ε-ε-ψβ-β, did not include distally located regulatory region(s) essential for ε-globin gene expression. Once separated from the 5'-regulatory sequences the remaining four embryonic genes (ε III, ε IV, ε V and ε VI) accumulated mutations and became pseudogenes.