Duplication of the γ-globin gene mediated by L1 long interspersed repetitive elements in an early ancestor of simian primates

Regions surrounding the single γ-globin gene of galago and the duplicated γ¹- and γ²-globin genes of gibbon, rhesus monkey, and spider monkey were sequenced and aligned with those from humans. Contrary to previous studies, spider monkey was found to have not one but two γ-globin genes, only one of which (γ²) is functional. The reconstructed evolutionary history of the γ-globin genes and their flanking sequences traces their origin to a tandem duplication of a DNA segment ≈5.5 kilobases long that occurred before catarrhine primates (humans, apes, and Old World monkeys) diverged from platyrrhines (New World monkeys), much earlier than previously thought. This reconstructed molecular history also reveals that the duplication resulted from an unequal homologous crossover between two related L1 long interspersed repetitive elements, one upstream and one downstream of the single ancestral γ-globin gene. Perhaps facilitated by the redundancy resulting from the duplication, the γ-globin genes escaped the selective constraints of embryonically functioning genes and evolved into fetally functioning genes. This view is supported by the finding that a burst of nonsynonymous substitutions occurred in the γ-globin genes while they became restructured for fetal expression in the common ancestor of platyrrhines and catarrhines.