Trends in Genetics
Accelerated evolution of the electron transport chain in anthropoid primates
Section snippets
Evolution of ETC gene complexes
ETC complexes have been evolving by adding new or losing old polypeptide subunits, and by amino acid replacements. Orthologous genes encoding all the current mammalian complexes can be identified in prokaryotes, although in prokaryotes each except complex II contains fewer genes. For example, complex I in Escherichia coli contains 14 subunits, whereas the mammalian version contains ∼45. A prokaryotic complex III typically contains three-to-four subunits, whereas the mammalian version contains
Co-evolution of ETC genes
Proteins typically interact with other proteins (e.g. Ref. [19]); consequently, amino acid replacements can affect not only the protein itself but also its ability to interact with other proteins. For example, in ETC complexes, the interactions are often between nuclear-genome-encoded- and mitochondrial-genome-encoded proteins. These intergenomic protein interactions make it possible to illustrate adaptive co-evolution experimentally by transferring mitochondria but not nuclei from one species
COX (Complex IV)
COX is the terminal – and probably rate-limiting 27, 28 – ETC complex that catalyzes the transfer of electrons from CYC to oxygen. Of the 13 subunits that form the mammalian version of COX, the three subunits that are encoded by mtDNA are orthologous to the subunits of prokaryotic COX. Mitochondrial subunits I and II perform the known catalytic functions COX (i.e. electron transfer and proton translocation). In turn, the ten subunits encoded by nuclear DNA are thought to be regulators of its
Evolution of function
To return to the question initially posed, how do the changes in complexes III, IV and CYC affect the function of the ETC? Several observations support the idea that positive selection has resulted in the functional co-adaptive evolution of ETC subunits in anthropoid primates. First, the changes in CYC in primates are concentrated in the parts of the molecule associated with function [46]. Second, changes in biochemical properties involved in the transfer of electrons from CYC to COX were
Concluding remarks
Substantial data now point to a remodeling of the anthropoid ETC. These molecular evolution changes are likely to be linked to the major phenotypic changes that are associated with anthropoid primates including enlarged neocortex, prolonged fetal (and therefore prenatal brain) development and extended lifespan – because all are supported by adaptations in aerobic energy production. The neocortex is a primary energy consumer, yet it must consume ‘clean’ energy in terms of minimized ROS
Acknowledgements
We thank members of the Grossman and Goodman laboratories for their interest and comments and the NIH and NSF for support during the course of this work.
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