Another look at mtDNA

By Razib Khan | April 8, 2012 6:55 pm

The new article in The American Journal of Human Genetics, A “Copernican” Reassessment of the Human Mitochondrial DNA Tree from its Root, is open access, so you should check it out. The discussion gets to the heart of the matter:

Supported by a consensus of many colleagues and after a few years of hesitation, we have reached the conclusion that on the verge of the deep-sequencing revolution…when perhaps tens of thousands of additional complete mtDNA sequences are expected to be generated over the next few years, the principal change we suggest cannot be postponed any longer: an ancestral rather than a “phylogenetically peripheral” and modern mitogenome from Europe should serve as the epicenter of the human mtDNA reference system. Inevitably, the proposed change could raise some temporary inconveniences. For this reason, we provide tables and software to aid data transition.

What we propose is much more than a mere clerical change. We use the Ptolemaian geocentric versus Copernican heliocentric systems as a metaphor. And the metaphor extends further: as the acceptance of the heliocentric system circumvented epicycles in the orbits of planets, switching the mtDNA reference to an ancestral RSRS will end an academically inadmissible conjuncture where virtually all mitochondrial genome sequences are scored in part from derived-to-ancestral states and in part from ancestral-to-derived states. We aim to trigger the radical but necessary change in the way mtDNA mutations are reported relative to their ancestral versus derived status, thus establishing an intellectual cohesiveness with the current consensus of shared common ancestry of all contemporary human mitochondrial genomes.

Note that the problem is not restricted to mtDNA. Indeed, in the much larger perspective of complete nuclear genomes in which comparisons are often currently made relative to modern human reference sequences, often of European origin, it seems worthwhile to begin considering, as valuable alternatives, public reference sequences of ancestral alleles (common in all primates) whereby derived alleles (common to some human populations) would be distinguished.

Perhaps the first generation or so of human molecular evolutionary genetics might be thought of as a “first draft.” A serviceable first draft which rendered in broad strokes the gist of the truth as we understand it, but lacking in some essential details.

On a minor note, there are some theoretical reasons why mtDNA did not yield much evidence for archaic admixture, which is clear in the nuclear genomics (e.g., higher rate of change due to lower effective population size, so more rapid extinction of ancient lineages). But perhaps now that the number of complete mtDNA genomes is increasing in size we might start to see “long branches,” which reflect the inferences generated from the ancient nuclear genomes.

  • Stephen

    At first glance, this looks like a sound revision. My only quibble is rhetorical. It takes a fair amount of gall to label your own revision “Copernican” even if it is in fact Copernican, and this clearly is not. It’s a high bar, no? Scientists tend to be looser with their metaphors than are English majors. Some things are iconic enough to deserve not to be used metaphorically.

  • Razib Khan

    yeah, i don’t like the rhetoric either…. lots of times if you use such rhetoric i wonder if there’s any substance behind it.

  • Charles Nydorf

    The revision is called Copernican because it represents a shift to a more natural frame of reference just as Copernicus shifted from a geocentric to a heliocentric model. Its not Copernican in the sense of being a massive scientific revolution and the authors do not imply that it is.

  • jb

    I’m not entirely sure I understand what is going on here, so let me ask directly in simple language: Is the “Reconstructed Sapiens Reference Sequence” basically an attempt to reconstruct the mitochondrial sequence of the famous “Mitochondrial Eve”, using Neanderthals as an outgroup?

  • Gisele

    jb: It is something like that. Here’s the problem as I see it: When complete human sequences are compared to a European one (CRS), they have many differences which are NOT mutations mixed in with actual mutations. The ratio is pretty high. When compared to the CRS, an A2a sequence, for instance, has 13 differences (43%) which are not mutations mixed in with 17 mutations (57%). A reference sequence which is closer to the root human one will alleviate most of that.


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About Razib Khan

I have degrees in biology and biochemistry, a passion for genetics, history, and philosophy, and shrimp is my favorite food. In relation to nationality I'm a American Northwesterner, in politics I'm a reactionary, and as for religion I have none (I'm an atheist). If you want to know more, see the links at


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