Research Highlights
-galactose: Human history revisited
Functional Glycomics (08 February 2007) | doi:10.1038/fg.2007.8Standfirst
The loss of 
-galactose in catarrhine primates might be explained by gene duplication and metabolic divergence, rather than by the outcome of a battle against pathogens.
Lack of 1,3galactosyltransferase (1,3GT) is a remarkable molecular feature distinguishing catarrhines (hominoids and Old World monkeys - humans, chimpanzees and macaques, among others) from all other mammalian species. 1,3GT catalyzes the addition of -galactose (Gal) to cell surface glycans. Catarrhines develop a strong antigenic reaction against Gal epitopes, which makes transplantations from mammals (such as pigs) to humans very difficult. Conventional theories state that catarrhines lost Gal epitopes because it gave them immunity or resistance to Gal-positive pathogens. Publishing in the Proceedings of the National Academy of Sciences, Koike et al. now present a radically different explanation of 1,3GT loss, using genomic information from several mammalian species.
Mammals such as pigs and mice carry a functional 1,3GT transferase encoded by the GGTA1 gene. Catarrhines possess two genes similar to GGTA1 that code for non-functional proteins. The unprocessed pseudogene (UPG) has the same exon-intron structure as GGTA1, while the processed pseudogene (PPG) does not contain introns. The PPG and UPG both share the same in-frame termination codon, suggesting that one evolved from the other, with UPG being the origin because its sequence contains introns.
However, Koike et al. have combined tools of evolutionary genetics with genomic data mining to suggest that the PPG originated early in the stem lineage to the last common ancestor of the catarrhines and platyrrhines (New World monkeys) before the UPG appeared. The PPG emerged through inaccurate retrotranscription of GGTA1 mRNA to produce a pseudogene that then existed in parallel with GGTA1. Physiological changes and functional compensation of 1,3GT by other glycosyltransferases finally led to the replacement of Gal. After this, GGTA1 accumulated mutations and evolved into the UPG.
The authors propose a detailed and empirically plausible model of the emergence of Gal antigenicity in humans. As Gal epitopes are predominantly expressed in olfactory tissues, the authors speculate that diminished olfaction in favor of visual perception in the catarrhines might have eased evolutionary constraints on GGTA1 mutation.
Original paper:
- Koike C et al. Functionally important glycosyltransferase gain and loss during catarrhine primate emergence. Proc Natl Acad Sci USA 104, 559–564 (2007). http://www.pnas.org/cgi/content/abstract/104/2/559 doi: 10.1073/pnas.0610012104
