Bioenergetics in human evolution and disease: implications for the origins of biological complexity and the missing genetic variation of common diseases

Abstract

Two major inconsistencies exist in the current neo-Darwinian evolutionary theory that random chromosomal mutations acted on by natural selection generate new species. First, natural selection does not require the evolution of ever increasing complexity, yet this is the hallmark of biology. Second, human chromosomal DNA sequence variation is predominantly either neutral or deleterious and is insufficient to provide the variation required for speciation or for predilection to common diseases. Complexity is explained by the continuous flow of energy through the biosphere that drives the accumulation of nucleic acids and information. Information then encodes complex forms. In animals, energy flow is primarily mediated by mitochondria whose maternally inherited mitochondrial DNA (mtDNA) codes for key genes for energy metabolism. In mammals, the mtDNA has a very high mutation rate, but the deleterious mutations are removed by an ovarian selection system. Hence, new mutations that subtly alter energy metabolism are continuously introduced into the species, permitting adaptation to regional differences in energy environments. Therefore, the most phenotypically significant gene variants arise in the mtDNA, are regional, and permit animals to occupy peripheral energy environments where rarer nuclear DNA (nDNA) variants can accumulate, leading to speciation. The neutralist-selectionist debate is then a consequence of mammals having two different evolutionary strategies: a fast mtDNA strategy for intra-specific radiation and a slow nDNA strategy for speciation. Furthermore, the missing genetic variation for common human diseases is primarily mtDNA variation plus regional nDNA variants, both of which have been missed by large, inter-population association studies.

Keywords: bioenergetics; evolution; mitochondria.

Figure 1.

Diagram of the migratory history of the human mtDNA haplogroups. Homo sapiens mtDNAs arose in Africa about 130 000–200 000 years before the present (YBP), with the first African-specific haplogroup branch being L0, followed by the appearance in Africa of lineages L1, L2 and L3. In northeastern Africa, L3 gave rise to two new lineages M and N. Only M and N mtDNAs successfully left Africa about 65 000 YBP and colonized all of Eurasia and the Americas. The diverse array of mtDNA lineages that M and N spawned are clustered together as macrohaplogroups M and N. The founders of macrohaplogroup M moved out of Africa through India and along the Southeast Asian coast down along the Malaysian peninsula and into Australia, generating haplogroups Q and M42 around 48 000 YBP. Subsequently, M moved north out of Southeast Asia to produce a diverse array of mtDNA lineages including haplogroups C, D, G and many other M haplogroup lineages. In northeast Asia, haplogroup C gave rise to haplogroup Z. The founders of macrohaplogroup N also move though Southeast Asia and into Australia, generating haplogroup S. In Asia, macrohaplogroup N mtDNAs also moved north to generate central Asian haplogroup A and Siberian haplogroup Y. In western Eurasia, macrohaplogroup N founders also moved north to spawn European haplogroups I, W, and X and in western Eurasia gave rise to sub-macrohaplogroup R. R moved west to produce the European haplogroups H, J, Uk, T, U, and V and also moved east to generate Australian haplogroup P and eastern Asian haplogroups F and B. By 20 000 YBP, mtDNA haplogroups C and D from M and A from N were enriched in northeastern Siberia and thus were positioned to migrate across the Bering land bridge (Beringia) to give rise to the first Native American populations, the Paleo-Indians. Haplogroups A, C, and D migrated throughout North America and on through Central American to radiate into South America. Haplogroup X, which is most prevalent in Europe but is also found in Mongolia, though not in Siberia, arrived in North America about 15 000 YBP, but remained in northern North America. Haplogroup B, which is not found in Siberia but is prevalent along the coast of Asia, arrived in North America about 12 000 to 15 000 YBP and moved through North and Central America and into South America, combining with A, C, D and X to generate the five dominant Paleo-Indian haplogroups (A − D + X). A subsequent migration of haplogroup A out of the Chukotka peninsula about 7000 to 9000 YBP gave rise to the Na-Déné (Athabaskins, Navajo, Apache, etc.). Subsequent movement across the Bering Strait, primarily carrying haplogroups A and D after 6000 YBP, produced the Eskimo and Aleut populations. Most recently, eastern Asian haplogroup B migrated south along the Asian coast through Micronesia and out into the Pacific to colonize all of the Pacific islands. Ages of migrations are approximated using mtDNA sequence evolution rates determined by comparing regional archeological or physical anthropological data with corresponding mtDNA sequence diversity. Since selection may have limited the accumulation of diversity in certain contexts, ages for regional migrations can best be estimated from the diversity encompassed within an individual regional or continental lineage, since selection would have had its greatest effect in enriching for the founding mtDNA haplotype, after which mtDNA mutations would accumulate randomly and thus become clock-like [42,43] (reproduced from http://www.mitomap.org, with permission).