Trends in Genetics

Trends in Genetics

Volume 20, Issue 11, November 2004, Pages 578-585
Journal home page for Trends in Genetics

Accelerated evolution of the electron transport chain in anthropoid primates

https://doi.org/10.1016/j.tig.2004.09.002Get rights and content

Mitochondria are both the power plant of the cell and a central integrator of signals that govern the lifespan, replication and death of the cell. Perhaps as a consequence, genes that encode components of the mitochondrial electron transport chain (ETC) are generally conserved. Therefore, it is surprising that many of these genes in anthropoid primates (New World monkeys, Old World monkeys and apes, including humans) have been major targets of darwinian positive selection. Sequence comparisons have provided evidence that marked increases of non-synonymous substitution rates occurred in anthropoid ETC genes that encode subunits of Complex III and IV, and the electron carrier molecule cytochrome c (CYC). Two important questions are: (i) how has evolution altered ETC function? and; (ii) how might functional changes in the ETC be linked to evolution of an expanded neocortical brain?

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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