Dr. Wallace and his colleagues have now decoded the full mitochondrial DNA from more than 1,000 people around the world and found signs of natural selection. By analyzing the changes in the DNA, they have been able to distinguish positive mutations, those selected because they are good or adaptive, from negative or harmful mutations. In today's issue of the journal Science, they report that several lineages of mitochondrial DNA show signs of positive selection.
These lineages are not found at all in Africans but occur in 14 percent of people in temperate zones and in 75 percent of those inhabiting Arctic zones. Dr. Wallace and his colleagues say this correlation is evidence that the lineages were positively selected because they help the body generate more heat.
Until now, most genetic change in the human population since it left Africa has been thought to be either random or just the elimination of harmful mutations. The evidence of the new analysis is that positive or adaptive selection "played an increasingly important role as people migrated out of Africa into temperate and Arctic Eurasia," the California team writes.
One implication is that everyone is adapted to a particular climate zone, and that moving to different zones may cause certain stresses. Mitochondria of the lineages found in Africa, Dr. Wallace suggests, may contribute the extra burden of certain diseases found among African-Americans, like diabetes and prostate cancer.
His reasoning is that African lineage mitochondria have never had to develop a mechanism for generating extra heat. So when an African-American and a European-American eat the same high calorie diet, the European's mitochondria burn some calories off as heat but the more efficient African mitochondria are liable to generate more fat deposition and oxidative damage, two results that could underlie the higher disease rates, Dr. Wallace said.
Separately, some of the European mitochondrial lineages appear to protect against Alzheimer's and Parkinson diseases and to be associated with greater longevity.
"Therefore," the California team writes, "to understand individual predisposition to modern diseases, we must also understand our genetic past, the goal of the new discipline of evolutionary medicine."
While many scientists study the genes of the human cell's nucleus, Dr. Wallace has focused on the tiny mitochondrial genome for 33 years. Along with the late Dr. Allan Wilson, he has pioneered the tracing of the 20 or so mitochondrial lineages found in the human population, all of which link back to a single individual known as the mitochondrial Eve.
Several other experts said that Dr. Wallace's ideas were promising but that the role of mitochondria in degenerative diseases had yet to be established. "It's a very attractive idea and may well turn out to be right, although the biochemical evidence of uncoupling differences between the mitochondrial lineages has yet to be nailed down," said Dr. Lawrence Grossman, a mitochondria expert at Wayne State University.
Dr. Mark Seielstad, a population geneticist at the Genome Institute of Singapore, said the positive selection was likely to have been a "major architect" in shaping mitochondria and that Dr. Wallace's work should throw open discussion of the subject.
Two experts on mitochondrial disease, Dr. Michael Brown of the Mercer University School of Medicine in Macon, Ga., and Dr. Gino Cortopassi of the University of California, Davis, said Dr. Wallace's ideas about African mitochondria made sense but had yet to reach practical significance. "We've not yet got to the stage of being able to give advice to African Americans," Dr. Brown said.
Dr. Wallace says that climatic selection may have operated on the human population from the moment it moved north of the African tropics. Most such pioneers died but two lineages, known as M and N, arose in northeast Africa some 65,000 years ago and might have been adapted to temperate climates. Almost everyone outside of sub-Saharan Africa has mitochondria descended from the M and N lineages.
| And that's the last three-quarters of Nicholas Wade's "Ice Age Ancestry May Keep Body Warmer and Healthier"
Also: Science magazine's "Ruiz-Pesini et al. 303 (5655): 223 Data Supplement -- Supporting Online Material"
Also: "Effects of Purifying and Adaptive Selection on Regional Variation in Human mtDNA"
Eduardo Ruiz-Pesini,¹ Dan Mishmar,¹ Martin Brandon,¹ ² Vincent Procaccio,¹ Douglas C. Wallace¹*;
A phylogenetic analysis of 1125 global human mitochondrial DNA (mtDNA) sequences permitted positioning of all nucleotide substitutions according to their order of occurrence. The relative frequency and amino acid conservation of internal branch replacement mutations was found to increase from tropical Africa to temperate Europe and arctic northeastern Siberia. Particularly highly conserved amino acid substitutions were found at the roots of multiple mtDNA lineages from higher latitudes. These same lineages correlate with increased propensity for energy deficiency diseases as well as longevity. Thus, specific mtDNA replacement mutations permitted our ancestors to adapt to more northern climates, and these same variants are influencing our health today.
¹ Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine, CA 92697-3940, USA.
² Information & Computer Science, Institute for Genomics & Bioinformatics, University of California, Irvine, CA 92697-3425, USA.
* To whom correspondence should be addressed. E-mail: dwallace@uci.edu
posted in articles on January 9, 2004 7:21 AM | t (0)
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