Enfermedades mitocondriales

Mitochondria. Immo E. Scheffler Copyright © 1999 John Wiley & Sons, Inc. ISBNs: 0-471-19422-0 (Hardback); 0-471-22389-1 (Electronic)

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MITOCHONDRIAL DNA POLYMORPHISMS AND ANTHROPOLOGY

8.1

INTRODUCTION

In 1987, Cann, Stoneking, and Wilson [1] published a paper on the analysis by restriction mapping of mtDNAs from 147 people, drawn from five widely spaced geographic populations (34Asians, 21 Australian aboriginals, 26 aboriginal New Guineans, 46 Caucasians, and 20 Africans). The scientific impact of this paper was enormous. The application of methods from molecular genetics to the study of primate and human evolution, with a focus on mitochondrial DNA, had been suggested by Brown [2], and several publications by Brown, Wilson, and colleagues had preceded the landmark 1987paper [3–5]. However, the large number and diversity of people represented in this paper provided convincing evidence for the potential strength of this approach in addressing questions about the relatively recent human evolution, about the origins of modern humans and about the migratory patterns of our ancestors. The abstract of the paper contained the eye-catching and provocative statement: “Allthese mitochondrial DNAs stem from one woman who is postulated to have lived about 200,000 years ago, probably in Africa.” Unfortunately, the popular press took this statement literally, and the misconception arose that she was the single ancestor of us all. The catchy headlines derived from this study certainly promoted interest in this field and popularized human evolution among the molecularbiologists who can relate more easily to a DNA sequence than to a jawbone. In the past decade the analyses have not only been vastly refined by the use of many more restriction enzymes, the application of the powerful polymerase chain reaction, and actual sequencing of defined regions, but human mtDNAs from the remotest areas of the globe have been analyzed, and one can only imagine what it wouldbe like to explain to a Chukchi from northeasternmost Siberia or a Yanomama from
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South America why their mtDNA is of such interest and how it proves that ultimately they all had descended from a mother in Africa. The biological and molecular basis for the value and fruitfulness of mitochondrial DNA sequence variations is derived from three facts. There is astrictly maternal mode of inheritance, hence no scrambling of information by recombination during sexual reproduction. The rate of evolution of mtDNA is estimated to be an order of magnitude greater than that of nuclear DNA, thus providing resolution on a time scale that is appropriate for human evolution: a few thousand years is sufficient time to generate informative variants. Finally, mtDNArepresents a distinct molecule that has been completely sequenced. It is abundant in cells (high copy number), and therefore easily accessible for experiments. The maternal mode of inheritance is an important consideration. There is universal agreement that nearly 100% of mtDNA in an individual is derived from the mother’s egg, and no complications are expected in the analysis of a pedigree of threeor more generations. However, phylogeny on an evolutionary time scale could well be influenced by the rare transmission of mtDNA from the paternal side, and a challenge of the current dogma was issued recently from a broad consideration of fertilization and the fate of the sperm mitochondria [6], and also from some very well-controlled studies with interspecies hybrid mice [7]. Since there wasevidence for biparental inheritance in interspecies hybrids, it became urgent to prove that this was the exception rather than the rule, and some such proof has been provided recently [8]. There is no argument over the observation that sperm mitochondria are found in the zygote shortly after fertilization. The most recent studies suggest, however, that paternal mtDNA is specifically eliminated in...