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Tiny Mitochondria Play Outsized Role in Human Evolution and Disease

Published on
Nov 4, 2015

Mitochondria are not only the power plants of our cells; these tiny structures also play a central role in our physiology. Furthermore, by enabling flexible physiological responses to new environments, mitochondria have helped humans and other mammals to adapt and evolve throughout the history of life on earth.

A pioneering scientist in mitochondrial biology, Douglas C. Wallace, PhD, synthesized evidence for the importance of mitochondria in a provocative Perspective article in the journal Cell.

Residing in large numbers outside the nucleus of every cell, mitochondria contain their own DNA, with unique features that “may require a reassessment of some of our core assumptions about human genetics and evolutionary theory,” concludes Dr. Wallace.

Dr. Wallace is the director of the Center for Mitochondrial and Epigenomic Medicine at The Children’s Hospital of Philadelphia and has investigated mitochondria for more than 40 years. In 1988, he was the first to show that mutations in mitochondrial DNA (mtDNA) can cause inherited human disease. His body of research has focused on how mtDNA mutations contribute to both rare and common diseases by disrupting bioenergetics — chemical reactions that generate energy at the cellular level.

Dr. Wallace and colleagues previously showed in the late 1970s that human mitochondrial DNA is inherited exclusively through the mother. They then used this knowledge to reconstruct the ancient migrations of women by comparing variation in mtDNA among populations throughout the world.

The vast majority of our 20,000 or so genes exist in the DNA within each cell’s nucleus, as distinct from the 13 protein-coding genes inside mtDNA. However, Dr. Wallace argues that mtDNA mutations provider faster and more flexible adaptations to changing environments than do nuclear DNA mutations. Most nuclear DNA mutations are deleterious and could imperil species’ survival.

Cells in the mother’s ovary that harbor the most deleterious mtDNA mutations can be eliminated by natural selection prior to fertilization. Thus only mild mtDNA variants, a subset of which may be potentially beneficial, are introduced into the population. The high mutation rate in mtDNA plus ovarian selection thus provide a powerful tool for humans (and animals) to adapt to an environmental change, without endangering a population’s overall survival.

Dr. Wallace argues that populations that expand into a marginal environmental space adapt their physiology through mtDNA mutation to better exploit the limited food sources and other resources in that environment. This permits prolonged occupation of the marginal environment, giving sufficient time for nuclear DNA mutations to generate anatomical structures appropriate for exploiting more abundant food resources in the new environment.

In his article, Dr. Wallace also proposed that mitochondria variation can result in crucial energy tradeoffs. He cited multiple studies that show that regional mtDNA variation correlates with predilection to a wide variety of metabolic and degenerative diseases, including Alzheimer and Parkinson disease, diabetes, obesity, and cardiovascular disease.

“Because mitochondria have such a crucial role in our physiology, changes in mitochondrial DNA can have profound effects on human biology,” he added.

For further details, click here to view the press release.