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nonhuman primates, Varki details the molecular bases and the putative functional consequences of more than 10 evolutionary genetic changes that seem to be specific to the human lineage. Overall, Varki’s analyses reveal multifaceted and oft-unexpected roles for cell-surface molecules in human biology and evolution. The sialic acid story also has broader evolutionary ramifications. For example, it implies that evolutionary “arms races” between hosts and pathogens can promote a form of “molecular mimicry” whereby different microorganisms convergently “reinvent” the use of Sias to help mask themselves from the surveillance of vertebrate immune systems. The Sias system also illustrates the profound challenges as well as the opportunities that likely will attend many such attempts to dissect other complex structural and functional components of human genome evolution.

Conventionally, “the human genome” refers to the full suite of DNA within the cellular nucleus. However, the nuclear genome has a diminutive partner—mitochondrial (mt) DNA—housed in the cellular cytoplasm. The prototypical human mitochondrial genome is only 16,569 base pairs in length (roughly a half-million-fold smaller than each nuclear genome), but what mtDNA lacks in size it more than makes up for in terms of copy number (thousands of mtDNA molecules reside in a typical somatic cell) and functional significance. Proteins and RNAs coded by the mitochondrial genome contribute critically to mitochondrial operations, which provide the cell with its chemical energy. The first complete sequence of human mtDNA was published 30 years ago (Anderson et al., 1981) and since then this “other” genome has become a model system for genealogical reconstructions of human demographic history (Cann et al., 1987) as well as for mechanistic appraisals of genomic structure and function in relation to human health (Wallace, 2005; McFarland et al., 2007). These topics have been thoroughly reviewed elsewhere, but in Chapter 7, Douglas Wallace uses such informational backdrop as a springboard to launch a bioenergetic hypothesis that ascribes a central role for energy flux in generating and maintaining complex biological structures such as the human brain. Wallace envisions a cyclical evolutionary process in which complex adaptations arise from a synergy between the information-generating power of energy flow and the information-accumulating capacity of selection-winnowed DNA. Under this evolutionary scenario, bioenergetic genes (notably those contributing to mitochondrial function) play key roles.

The ongoing genomics revolution in biology that began little more than decade ago is opening new windows not only to the genes that make us human but also to the nature and significance of genetic differences between extant human populations now living in different geographical regions of the planet. As a part of this global monitoring effort by the scientific community (Rosenberg et al., 2002; Frazer et al., 2007), Katarzyna



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