Fetal Globin Expression in New World Monkeys

Abstract

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 gamma-globin expression was fetal in these animals. The globins were identified by a combination of chemical sequencing and mass spectrometric analysis. Since gamma-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 gamma-globin gene underwent tandem duplication during the same evolutionary epoch, in accord with a model that suggests that the downstream duplicated gamma-gene (gamma2) was free to acquire the mutations necessary for fetal recruitment. Mass spectrometric analysis of tryptic digests of the gamma-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 gamma2-globin in Cebus was expressed to a far greater extent than gamma1-globin, supporting inferences drawn from a study of the promoter sequences. A "pre-gamma"-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 gamma-globin polypeptide. This work provides biochemical evidence of an evolutionary trend in the platyrrhines to alter the duplicated gamma-globin gene locus so that only one gamma-globin polypeptide is expressed.

A Maximum Likelihood Method for Detecting Functional Divergence at Individual Codon Sites, with Application to Gene Family Evolution

“…Expression of e is embryonic in all placental mammals, while c expression is embryonic only in nonprimate placental mammals and prosimian primates, being delayed to fetal expression in simian primates (Johnson et al 1996).…”

“…Fitch et al (1991) suggested that the initial gene duplication event was followed by divergence of e and c for different ''embryonic niches.'' Later (35 to 55 MYA), a second case of genetic co-option occurred when embryonically expressed c was recruited for fetal expression in the early simian lineage Tagle et al 1988;Meireles et al 1995;Johnson et al 1996). The objective of our analysis was, first, to test for divergence in selective pressure between e and c and, second, to identify sites consistent with this type of selective pressure if they existed.…”

“…Here we describe a model that allows variation in d N /d S among sites, with a fraction of sites evolving under divergent selective pressures between two clades following a co-option event. We implement the model in the maximum likelihood framework and apply it to two cases of evolution by gene duplication: (i) the e and c globin gene family (Meireles et al 1995;Johnson et al 1996;Fitch et al 1991) and (ii) the eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN) gene family (Zhang et al 1998;Zhang and Rosenberg 2002).…”

Gene Conversion may aid Adaptive Peak Shifts

“…This situation is especially evident in extant catarrhines, which express both 1 and 2 ( 1' 2) in fetal life (Bunn & Forget, 1986). However in platyrrhines, 2 is preferentially expressed and 1 is either non-or very weakly expressed (Johnson et al, 1996;Chiu et al, 1996Chiu et al, , 1999. Although there is no direct evidence for relative "tness values of the di!erent stages, it can be speculated that the evolution of fetal genes was associated with extended fetal gestational periods in simian primates.…”

Phylogenetic comparisons suggest that distance from the locus control region guides developmental expression of primate β-type globin genes

“…It should be noted that the Aotus fetal and postnatal samples that were examined in ref. 19 were from A. azarae, a close relative of A. infulatus.…”