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(Weatherall et al., 1984). Protein kinases are also subject to disorder-producing malfunctions, with more than 160 different kinases having been implicated in cancers by their common association with particular tumor types and 80 kinases having been associated at least provisionally with various other disease conditions (Manning et al., 2002). Similarly, research suggests that occasional misregulation of miRNA molecules contributes to the total pool of human metabolic disorders, including perhaps DiGeorge syndrome as well as some cancers (Alvarez-Garcia and Miska, 2005).

Why an intelligent and loving designer would have infused the human genome with so many potential (and often realized) regulatory flaws is open to theological debate. Any such philosophical discussion should probably include the issue of whether the designer was fallible (and if so, why?). It should also address whether the designer might have recognized his own engineering fallibility, as perhaps evidenced, for example, by the DNA and RNA surveillance mechanisms that catch some (but not all) of the numerous molecular mistakes.

From an evolutionary perspective, such genomic flaws are easier to explain. Occasional errors in gene regulation and surveillance are to be expected in any complex contrivance that has been engineered over the eons by the endless tinkering of mindless evolutionary forces: mutation, recombination, genetic drift, and natural selection. Again, the complexity of genomic architecture would seem to be a surer signature of tinkered evolution by natural processes than of direct invention by an omnipotent intelligent agent.

mtDNA

Mitochondria are the only cytoplasmic organelles in humans to house their own DNA (mtDNA). A prototypical molecule of human mtDNA is 16,569 bp long. It is a closed circle of 37 maternally inherited genes, 22 of which encode tRNAs, 13 specify polypeptides, and 2 encode rRNAs.

Mitochondria are the primary seat of energy production in cells. The principal biochemical pathway in mitochondria by which this is carried out is oxidative phosphorylation, of which the respiratory chain is a key component. The respiratory chain consists of five enzyme complexes (I-V) plus coenzyme Q and cytochrome c. Complexes I and II oxidize NADH and succinate, respectively; complexes I, III, and IV pump protons to effect an electrochemical gradient; and complex V uses energy from that gradient to synthesize adenosine triphosphate from adenosine diphosphate. A remarkable fact is that four of these five enzyme complexes are composed of combinations of polypeptides from the mitochondrial and nuclear genomes (Graff et al., 1999). In complex IV, for example, 3 of the 13 polypeptides are encoded by mitochondrial loci (COI, COII,



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