Functionally important glycosyltransferase gain and loss during catarrhine primate emergence

A glycosyltransferase, alpha 1,3galactosyltransferase, catalyzes the terminal step in biosynthesis of Gal alpha 1,3Gal beta 1-4GlcNAc-R (alpha Gal), 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, aGal is not normally found in catarrhine primates (Old World monkeys and apes, including humans), all of which produce anti-alpha Gal antibodies from infancy onward. Natural selection favoring enhanced resistance to alpha Gal-positive pathogens has been the primary reason offered to account for the loss of aGal 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 GGTA1 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 aGal-positive pathogens could then have accelerated the replacement of aGal-positive catarrhines by alpha Gal-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.