title: Colloquium paper: bioenergetics, the origins of complexity, and the ascent of man.
abstract: Complex structures are generated and maintained through energy flux. Structures embody information, and biological information is stored in nucleic acids. The progressive increase in biological complexity over geologic time is thus the consequence of the information-generating power of energy flow plus the information-accumulating capacity of DNA, winnowed by natural selection. Consequently, the most important component of the biological environment is energy flow: the availability of calories and their use for growth, survival, and reproduction. Animals can exploit and adapt to available energy resources at three levels. They can evolve different anatomical forms through nuclear DNA (nDNA) mutations permitting exploitation of alternative energy reservoirs, resulting in new species. They can evolve modified bioenergetic physiologies within a species, primarily through the high mutation rate of mitochondrial DNA (mtDNA)-encoded bioenergetic genes, permitting adjustment to regional energetic environments. They can alter the epigenomic regulation of the thousands of dispersed bioenergetic genes via mitochondrially generated high-energy intermediates permitting individual accommodation to short-term environmental energetic fluctuations. Because medicine pertains to a single species, Homo sapiens, functional human variation often involves sequence changes in bioenergetic genes, most commonly mtDNA mutations, plus changes in the expression of bioenergetic genes mediated by the epigenome. Consequently, common nDNA polymorphisms in anatomical genes may represent only a fraction of the genetic variation associated with the common "complex" diseases, and the ascent of man has been the product of 3.5 billion years of information generation by energy flow, accumulated and preserved in DNA and edited by natural selection.
authors.affiliation: Organized Research Unit for Molecular and Mitochondrial Medicine and Genetics and Departments of Ecology and Evolutionary Biology, Biological Chemistry, and Pediatrics, University of California, Irvine, CA 92697-3940, USA.
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Wallace
mesh_terms: D000818:Animals; D005075:Biological Evolution; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004563:Electrochemistry / Q000379:methods; D004734:Energy Metabolism; D006801:Humans; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D012641:Selection, Genetic
chemical_list: D004247:DNA
references.citation: Sci Am. 2003 Apr;288(4):70-7
references.pmid: 12661318
references.citation: Epigenetics. 2009 Aug 16;4(6):399-403
references.pmid: 19755853
references.citation: Science. 2008 Feb 15;319(5865):958-62
references.pmid: 18276892
references.citation: Annu Rev Genet. 2005;39:359-407
references.pmid: 16285865
references.citation: Nature. 2006 Aug 3;442(7102):563-7
references.pmid: 16885984
references.citation: Curr Genet. 1987;12(2):81-90
references.pmid: 2896550
references.citation: Science. 2007 Jun 1;316(5829):1331-6
references.pmid: 17463246
references.citation: PPAR Res. 2007;2007:74364
references.pmid: 17389766
references.citation: J Clin Endocrinol Metab. 2005 Feb;90(2):1176-80
references.pmid: 15562023
references.citation: Cold Spring Harb Symp Quant Biol. 2009;74:383-93
references.pmid: 19955254
references.citation: Proc Natl Acad Sci U S A. 1987 Nov;84(21):7580-4
references.pmid: 2823266
references.citation: Nat Genet. 2000 Sep;26(1):76-80
references.pmid: 10973253
references.citation: Proc Biol Sci. 2009 Oct 7;276(1672):3447-55
references.pmid: 19586946
references.citation: Diabetes. 2003 Mar;52(3):895-8
references.pmid: 12606537
references.citation: Diabetologia. 2001 Dec;44(12):2220-6
references.pmid: 11793024
references.citation: Science. 2007 Jun 1;316(5829):1341-5
references.pmid: 17463248
references.citation: Science. 2010 Jan 15;327(5963):302-5
references.pmid: 20007865
references.citation: J Med Invest. 2006 Aug;53(3-4):218-22
references.pmid: 16953057
references.citation: Nature. 2009 Nov 19;462(7271):272-4
references.pmid: 19924185
references.citation: Nature. 1987 Jan 1-7;325(6099):31-6
references.pmid: 3025745
references.citation: Free Radic Biol Med. 2008 Mar 15;44(6):921-37
references.pmid: 18155672
references.citation: Metabolism. 2006 May;55(5):578-86
references.pmid: 16631432
references.citation: Ann Neurol. 2008 Jan;63(1):35-9
references.pmid: 17886296
references.citation: Autophagy. 2008 May;4(4):534-6
references.pmid: 18376135
references.citation: PLoS Genet. 2006 Aug;2(8):e128
references.pmid: 16895436
references.citation: Sci Am. 2008 Nov;299(5):62-7
references.pmid: 18998348
references.citation: PLoS Biol. 2008 Jan;6(1):e10
references.pmid: 18232733
references.citation: J Mol Evol. 1982;18(4):225-39
references.pmid: 6284948
references.citation: J Mol Evol. 1983;19(3-4):255-71
references.pmid: 6310133
references.citation: Annu Rev Biochem. 2007;76:781-821
references.pmid: 17506638
references.citation: PLoS Genet. 2009 May;5(5):e1000474
references.pmid: 19424428
references.citation: Sci Am. 2009 Sep;301(3):54-61
references.pmid: 19708528
references.citation: Am J Hum Genet. 2008 Aug;83(2):254-60
references.pmid: 18674747
references.citation: J Mol Evol. 1991 Dec;33(6):543-55
references.pmid: 1685753
references.citation: Nature. 2007 Feb 22;445(7130):881-5
references.pmid: 17293876
references.citation: Genes Dev. 2009 Aug 1;23(15):1714-36
references.pmid: 19651984
references.citation: Nature. 2007 May 24;447(7143):433-40
references.pmid: 17522677
references.citation: Annu Rev Pathol. 2010;5:297-348
references.pmid: 20078222
references.citation: Mitochondrion. 2010 Jan;10(1):12-31
references.pmid: 19796712
references.citation: Gene. 2006 Aug 15;378:11-8
references.pmid: 16828987
references.citation: Genes Brain Behav. 2008 Oct;7(7):754-60
references.pmid: 19125863
references.citation: Science. 2007 Jun 1;316(5829):1336-41
references.pmid: 17463249