Mitochondrial DNA: a maternal gift

Marshall Lichtman
Rochester, New York, United States


Ancestry tree traced back to Mitochondrial Eve

Human haplogroup tree rooted at Mitochondrial Eve. By Wapondaponda. 2009. Via Wikimedia. CC BY-SA 3.0

DNA is arrayed on twenty-three pairs of chromosomes in human cell nuclei. It is coiled tightly around proteins called histones that together with DNA form a chromosome. The largest chromosome carries several thousand genes and the smallest several hundred. DNA is so tightly wound that uncoiled from a single cell nucleus it would be over six feet long. The latter estimate is derived from the length of a base pair times the number of base pairs in the genome of a cell. The double strands of DNA in a cell nucleus contain about three billion pairs of nucleic acid bases. Our approximately 19,000 protein-encoding genes occupy about one and one-half percent of the length of a cell’s DNA. The remainder is referred to as non-coding DNA.

Much of the non-coding DNA plays a role as (1) regulating agents such as promoters, enhancers, silencers, and insulators, assigned to modify the expression of protein-coding genes; or (2) encoding various types of RNA that, among other things, regulate gene function. These complexities account for a single gene’s ability to direct the synthesis of several different proteins. Since every cell has the same DNA, regulation of gene expression is profoundly important as it determines which among the approximately 200 different cell types in the human body a cell becomes: for example, an osteocyte, a hepatocyte, or a motor neuron. Much of the roughly 98.5 percent of non-protein-encoding DNA is given to regulating the gene expression of the remaining 1.5 percent that represents protein-encoding genes. A small fraction of non-coding DNA is devoted to forming telomeres that function as the terminal ends, or caps, of chromosomal DNA.

Understandably, few people appreciate that we have DNA outside our cell nuclei: mitochondrial (mt)DNA. The mitochondria are subcellular structures present in the cytoplasm of cells and responsible for generating energy. This process provides the power for skeletal muscle contraction (locomotion) and other activities that require biochemical energy. In a mitochondrion, DNA is arrayed in a doughnut-like, circular single chromosome, which contains thirty-seven genes dedicated to, among other things, encoding proteins, notably enzymes that convert energy sources derived from food into chemical energy to drive processes such as the contraction of heart and smooth muscle. MtDNA has many differences from nuclear DNA. It is circular, not linear; and has a higher mutation rate than nuclear DNA.

A critical feature of mtDNA is that it is derived only from one’s mother since it is the egg’s contribution of a large number of mitochondria to the fertilized egg, the zygote, that persists, not the very small contribution of the sperm. Variation in maternal mtDNA can be traced back over generations and thus has been used to characterize our matrilineal ancestry. Since it has been passed from mother to child from time immemorial, genealogists and population geneticists have used the nature of mtDNA to trace our primordial mother, referred to as “mitochondrial Eve,” using the Hebrew biblical first woman’s name as a metaphor.

MtDNA has been traced back some 185,000 years to South or East Africa, where it is posited that mitochondrial Eve represented the woman from whom all current living humans descended. This approximation is buttressed by being dated after the appearance of Homo sapiens and before the “Out of Africa Theory” that describes the migration of Homo sapiens from Africa to Europe, Southern Asia, and Australia. The mitochondrial Eve concept does not mean that this was the first woman (hence, it is a gross misnomer) nor the only living female at the time, nor the first member of a new species. She is defined as the most recent identifiable woman from whom all living humans descend in an unbroken line through their mothers. Looking back, all existing genetic lines converge on this one woman. It is the result of the mitochondrial Eve having had at least two daughters who have unbroken female lineages through the present time. The size of the ancient human population in that period never decreased below thousands based on studies of nuclear DNA.

So when thinking about DNA, recall that a very small, but critical set of genes resides outside the nucleus in mitochondria and gives us our oomph! Genealogists and population geneticists can use a structure passed only from father to son, the Y chromosome, to look for the proverbial Y-chromosomal Adam. In this metaphorical story, Y-chromosomal Adam and mitochondrial Eve were very unlikely to have known each other.

Since A. C. Wilson and his colleagues published their paper on mitochondrial DNA and human evolution in 1987, counter-arguments have been raised as to the validity of the concept and the techniques to trace matrilineage using mtDNA, the dating of the time of mitochondrial Eve’s and the Y-chromosomal Adam’s existence, and of Africa as the sole site of the evolution of Homo Sapiens and their migration to other continents. Today, there is a consensus, albeit not unanimous, that mitochondrial Eve and Y-chromosomal Adam lived about 175,000 to 200,000 years ago in Africa, from where Homo sapiens dispersed.



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MARSHALL A. LICHTMAN, MD, MACP, is Professor Emeritus of Medicine and of Biochemistry and Biophysics and Dean Emeritus, the School of Medicine and Dentistry, the University of Rochester Medical Center. He has served on the Board of Governors of the American Red Cross (1990-96) and was a Trustee of the State University of New York. (2010-18). He received the Wallace H. Coulter Award for Lifetime Achievement by the American Society of Hematology in 2017.


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