Involvement of mitochondrial DNA in the initiation of autoimmune disease ???

Dear anonymous 6th-grade teacher,

This sounds like a very astute student; I wonder if one or both of her parents might have careers in some aspect of biological science or medicine? The original report of using mitochondrial DNA to trace human ancestry back to the original “African Eve”, published in Science or Nature back in the 1980s, was subsequently found to be naïve. I’ve searched for, but cannot find, that original paper (author was an evolutionary geneticist from California, as I recall). I did find two relevant follow-up papers (1989 & 1996), which answer part of your question (summaries pasted below). Remember, the first human genome was not fully sequenced until well after 1996, so these papers precede that accomplishment by several years. In recent years, far more has been learned from fossil DNA — about the Great Human Diaspora.

As with everything in science — what starts out as “appearing simple” — winds up being far more complex, by many orders of magnitude. The myth that “all mtDNA always comes from the mother” is no longer true; there are a few published cases where they found the mtDNA derived 100% from the father, and other cases where some percentage of mtDNA is paternally-derived. So, to start with, the mother’s mitochondria are NOT ALWAYS the only ones that get passed on to her children…

Then, our (nuclear) genomic DNA (gDNA) — as well as our mtDNA today — represents what has been passed down from an unknown small number of original Homo sapiens when they first appeared ~300,000 years ago. But, of course, with mutations and chromosomal rearrangements (that have occurred over about 15,000 generations of modern humans) — things DO change A LOT over that amount of time. And, quite remarkably, DNA from fossil bones has shown us that there are five fundamental “isolated geographic groups” in the world: African, Asian, Caucasian, Oceanian and Amerindian — from which all ethnic groups on Earth originate.

From complicated mathematical extrapolations, researchers have even estimated the approximate number of men and number of women that “appear to have participated” in the “original genetic bottleneck” of a tribe migrating out of Africa toward southeast Asia, or through the Caucasus Mountains into (present-day) Europe, or across the Siberia Strait into the Americas, etc. But, even this today, is far too simplistic, due to back-migrations and cross-group admixtures (among modern humans, Denisovans and Neanderthals).

To re-summarize this study and editorial [see attached] — when mitochondria become “stressed” by one or another environmental adversity, some of the (circular) mtDNA — breaks up into small fragments, and the study found that VDAC oligomerization in the mitochondrial outer membrane, causes leaks when mitochondria are stressed — resulting in these mtDNA fragments leaking out into the cytosol, where “self-antibodies” to one’s own mtDNA are then formed, perhaps playing a role in initiation of one or another autoimmune disease. Authors thus suggest VDAC as a potential drug target to prevent this pathology from occurring. 😊

Am J Hum Genet. 1989 Jan;44(1):73-85.

Origin and differentiation of human mitochondrial DNA.

Excoffier L1, Langaney A.

Author information


A recent study of mitochondrial DNA (mtDNA) polymorphism has generated much debate about modern human origins by proposing the existence of an “African Eve” living 200,000 years ago somewhere in Africa. In an attempt to synthesize information concerning human mtDNA genetic polymorphism, all available data on mtDNA RFLPs have been gathered. A phylogeny of the mtDNA types found in 10 populations reveals that all types could have issued from a single common ancestral type. The distribution of shared types between continental groups indicates that caucasoid populations could be the closest to an ancestral population from which all other continental groups would have diverged (This is now all proven to be wrong) A partial phylogeny of the types found in five other populations also demonstrates that the myth of an African Eden was based on an incorrect “genealogical tree” of mtDNA types. Two measures of molecular diversity have been computed on all samples on the basis of mtDNA type frequencies, on one hand, and on the basis of the number of polymorphic sites in the samples, on the other. A large discrepancy is found between the two measures except in African populations; this suggests the existence of some differential selective mechanisms. The lapse of time necessary for creating the observed molecular diversity from an ancestral monomorphic population has been calculated and is found generally greater in Oriental and caucasoid populations. Implications concerning human mtDNA evolution are discussed. PMID: 2562823 PMCID: PMC1715476

Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):13859-63.

Misconceptions about mitochondria and mammalian fertilization: implications for theories on human evolution.

Ankel-Simons F1, Cummins JM.

Author information


In vertebrates, inheritance of mitochondria is thought to be predominantly maternal, and mitochondrial DNA analysis has become a standard taxonomic tool. In accordance with the prevailing view of strict maternal inheritance, many sources assert that during fertilization, the sperm tail, with its mitochondria, gets excluded from the embryo. This is incorrect. In the majority of mammals—including humans—the midpiece mitochondria can be identified in the embryo even though their ultimate fate is unknown. The “missing mitochondria” story seems to have survived–and proliferated-unchallenged in a time of contention between hypotheses of human origins, because it supports the “African Eve” model of recent radiation of Homo sapiens out of Africa. We will discuss the infiltration of this mistake into concepts of mitochondrial inheritance and human evolution. PMID: 8943026 PMCID: PMC19448

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