Functionally important glycosyltransferase gain and loss during catarrhine primate emergence

A glycosyltransferase, α1,3galactosyltransferase, catalyzes the terminal step in biosynthesis of Galα1,3Galβ1-4GlcNAc-R (αGal), an oligosaccharide cell surface epitope. This epitope or antigenically similar epitopes are widely distributed among the different forms of life. Although abundant in most mammals, αGal is not normally found in catarrhine primates (Old World monkeys and apes, including humans), all of which produce anti-αGal antibodies from infancy onward. Natural selection favoring enhanced resistance to αGal-positive pathogens has been the primary reason offered to account for the loss of αGal in catarrhines. Here, we question the primacy of this immune defense hypothesis with results that elucidate the evolutionary history of GGTA1 gene and pseudogene loci. One such locus, GGTA1P. a processed (intronless) pseudogene (PPG), is present in platyrrhines, i.e.. New World monkeys, and catarrhines but not in prosimians. PPG arose in an early ancestor of anthropoids (catarrhines and platyrrhines), and GGTA1 itself became an unprocessed pseudogene in the late catarrhine stem lineage. Strong purifying selection, denoted by low nonsynonymous substitutions per nonsynonymous site/synonymous substitutions per synonymous site values, preserved CCTA1 in noncatarrhine mammals, indicating that the functional gene product is subjected to considerable physiological constraint. Thus, we propose that a pattern of alternative and/or more beneficial glycosyltransferase activity had to first evolve in the stem catarrhines before GGTA1 inactivation could occur. Enhanced defense against αGal-positive pathogens could then have accelerated the replacement of αGal-positive catarrhines by αGal-negative catarrhines. However, we emphasize that positively selected regulatory changes in sugar chain metabolism might well have contributed in a major way to catarrhine origins.