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ing anti-Neu5Gc antibodies, generating a novel “xeno-autoantigen” situation. Taken together, these data suggest that both the genes associated with Sia biology and the related impacts of the environment comprise a relative “hot spot” of genetic and physiological changes in human evolution, with implications for uniquely human features both in health and disease.

The theory of evolution via descent by natural selection explains the  diversity of life on Earth (Darwin, 1859). Huxley (1863) and Darwin (1871b) correctly predicted that the “great apes” (chimpanzees, bonobos, gorillas, and orangutans, i.e., nonhuman hominids, NHHs1) are our closest evolutionary cousins. Indeed, chimpanzees were once considered good models for human disease. However, there are major differences between humans and NHHs in the incidence and severity of various diseases, beyond those explained by anatomical reasons (Varki, 2000; Varki and Altheide, 2005; Finch, 2010).

Scholars of mathematical, physical, and chemical sciences sometimes ask why biology does not have the kinds of universal laws that underpin their disciplines. The reason is that although biological systems operate under mathematical, physical, and chemical principles, evolutionary mechanisms of random mutation and deterministic selection do not generate consistent or universal outcomes. Of course, a single origin of life combined with physical constraints resulted in some near-universals, such as the paradigm that nucleic acid sequences encode protein sequences (Crick, 1970). Another apparent biological universal is that all nucleated cells in nature are covered with a dense and complex coating of sugar chains (glycans) (Varki, 2006), which have numerous biological roles (Varki and Lowe, 2009). Thus, natural selection repeatedly recruited glycans as being the best molecules for decorating the cell surface. Here I focus on one aspect of cellular glycan coating that changed during human evolution, potentially explaining aspects of human uniqueness, in health and in disease.

1

The term “great ape” refers to chimpanzees, bonobos, gorillas, and orangutans, and the term “hominoid” also includes lesser apes. Neither term is now taxonomically valid. The term “hominid” is now being used for the clade including humans and great apes. I here mostly use the term “nonhuman hominid” (NHH) in place of great ape and the term “hominin” for branches of the human-like lineages after the common ancestor with chimpanzees.



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