Fetal Globin Expression in New World Monkeys

Reverse phase chromatography of the globin chains of adult, newborn, and fetal erythrocytes from three species of New World monkeys ( Cebus apella, Aotus azarae, and Callithrix jacchus ) representing three of the seven platyrrhine clades showed that γ-globin expression was fetal in these animals. The globins were identified by a combination of chemical sequencing and mass spectrometric analysis. Since γ-globin expression is fetal in the other major simian branch, the catarrhines, but embryonic in prosimian primates and nonprimate placental mammals, the evolution of fetal recruitment can now be assigned to the period between the simian-prosimian divergence (55 million years ago) and the platyrrhine-catarrhine divergence (35 million years ago). The γ-globin gene underwent tandem duplication during the same evolutionary epoch, in accord with a model that suggests that the downstream duplicated γ-gene (γ2) was free to acquire the mutations necessary for fetal recruitment. Mass spectrometric analysis of tryptic digests of the γ-globins verified the amino acid sequences deduced from genomic sequencing. Detailed analysis of high performance liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry data showed that γ2-globin in Cebus was expressed to a far greater extent than γ1-globin, supporting inferences drawn from a study of the promoter sequences. A “pre-γ”-globin was observed in C. apella and shown to be primarily the glutathionyl adduct. The other species, A. azarae and C. jacchus, also express only one γ-globin polypeptide. This work provides biochemical evidence of an evolutionary trend in the platyrrhines to alter the duplicated γ-globin gene locus so that only one γ-globin polypeptide is expressed.