What remains of the neutral mtDNA molecular clock if mtDNA haplotypes are functionally different?

What remains of the neutral mtDNA molecular clock if mtDNA haplotypes are functionally different?

Letter to Editor (submitted preprint)

JAMA Psychiatry

Dear Editor,

I read with great interest your recent paper on mtDNA haplogroups in autism by Chalkia et al. (1). The paper has expressed a consistent view by the senior author D. Wallace since his 1991 paper by Merriwether et al that mtDNA variations are not neutral (2). I quote from the new paper: “The various mtDNA haplogroup lineages arose and radiated within regional indigenous populations and are functionally different. Therefore, their proliferation within specific environments was due to adaptive selection.”

The first mtDNA phylogenetic tree was published in 1983 by Johnson et al including Wallace as coauthor (3). Figure 7 in that paper shows two possible roots of a mtDNA tree, one in Asia and one in Africa. The legend says that one has to assume the molecular clock in order to root the tree in Africa, and that if there is no molecular clock and if Africans have higher mutation rate, then the root would be placed in Asia. The paper in fact concluded that the root is in Asia.

Even though Wallace said in the 1988 Newsweek article (4) that he had evidence for rooting the mtDNA tree not in Africa, he had in his 1991 formal publication on the topic fully supported the Out of Africa model. A recent talk by Wallace in this video indicates that he believes that there is a mtDNA molecular clock. https://www.dnalc.org/view/15178-Mitochondrial-DNA-and-the-molecular-clock-Douglas-Wallace.html

It is my understanding that the molecular clock can only be explained by the neutral theory. Most variations would have to be neutral for the molecular clock to be real. It is now however an open secret that the universal molecular clock is not real, merely a mirage as termed by F. Ayala (5). Wallace’s own papers including this new one, by showing mtDNA haplotypes to be functionally selected, also disproved a mtDNA molecular clock (and in turn the Africa Eve model).

I therefore find it extremely puzzling that Wallace can hold two mutually exclusive views. He has first-hand full knowledge that different mtDNA haplotypes are functionally different or under “adaptive selection”, and yet he believes the mtDNA clock and its necessary deduction the Africa Eve model.

It is therefore unfortunate that the new paper made no mention of the implications of the mtDNA-autism connection on the neutral molecular clock and the Africa Eve model.

References:

1.    Chalkia et al., (2017) Association Between Mitochondrial DNA Haplogroup Variation and Autism Spectrum Disorders. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.2604. Published online August 23, 2017.

2.    Merriwether D A, Clark A G, Ballinger S W, Schurr T G, Soodyall H, Jenkins T, Sherry S T, Wallace D C(1991) The structure of human mitochondrial DNA variation. J. Mol. Evol. 33:543–555.

3.    Johnson M J, Wallace D C, Ferris S D, Rattazzi M C, Cavalli-Sforza L L(1983) Radiation of human mitochondria DNA types analyzed by restriction endonuclease cleavage patterns. J Mol Evol 19:255–271.

4.    Tierney, et al., (1988) The search for Adam and Eve. 111, 46-52.

5.    Ayala, F. (1999) Molecular mirages. Bioassays, 21, 71-75