A "Copernican" reassessment of the human mitochondrial DNA tree from its root

Abstract

Mutational events along the human mtDNA phylogeny are traditionally identified relative to the revised Cambridge Reference Sequence, a contemporary European sequence published in 1981. This historical choice is a continuous source of inconsistencies, misinterpretations, and errors in medical, forensic, and population genetic studies. Here, after having refined the human mtDNA phylogeny to an unprecedented level by adding information from 8,216 modern mitogenomes, we propose switching the reference to a Reconstructed Sapiens Reference Sequence, which was identified by considering all available mitogenomes from Homo neanderthalensis. This "Copernican" reassessment of the human mtDNA tree from its deepest root should resolve previous problems and will have a substantial practical and educational influence on the scientific and public perception of human evolution by clarifying the core principles of common ancestry for extant descendants.

Figure 1

Schematic Representation of the Human mtDNA Phylogeny within Hominini (Left) Hominini phylogeny illustrating approximate divergence times of the studied species. The positions of the RSRS and the putative Reconstructed Neanderthal Reference Sequence (RNRS) are shown. (Right) Magnification of the human mtDNA phylogeny. Mutated nucleotide positions separating the nodes of the two basal human haplogroups L0 and L1′2′3′4′5′6 and their derived states as compared to the RSRS are shown. The positions of the rCRS and the RSRS are indicated by golden and a green five-pointed stars, respectively. Accordingly, the number of mutations counted from the rCRS (NC_012920) or the RSRS (Sequence S1) to the L0d1c1b (EU092832) and H4a1a (HQ860291) haplotypes retrieved from a San and a German, respectively, are marked on the golden and green branches. The principle of equidistant star-like radiation from the common ancestor of all contemporary haplotypes is highlighted when the RSRS is preferred over the rCRS as the reference sequence.

Figure 2

Human mtDNA Phylogeny A schematic representation of the most parsimonious human mtDNA phylogeny inferred from 18,843 complete mtDNA sequences with the structure shown explicitly for bifurcations that occurred 40,000 years before present (YBP) or earlier, and a graph showing the explosion of haplogroups since then. The y axis indicates the approximate number of haplogroups from each time layer that have survived to nowadays. The upper and lower x axes of the rooted tree are scaled according to the number of accumulated mutations since the RSRS and the corresponding coalescence ages, respectively.

Figure 3

Haplogroup H4 internal cladistic structure (Left) Haplogroup H4 as first reported. Mutations in bold were considered diagnostic for the haplogroup. (Right) Haplogroup H4 as currently resolved with a total of 236 H4 mitogenomes. An almost perfect resolution of the nested hierarchy is achieved. Additional haplogroups suggested herein are shown in yellow. Control-region mutations are noted in blue.