The Molecular Dissection of mtDNA Haplogroup H Confirms That the Franco-Cantabrian Glacial Refuge Was a Major Source for the European Gene Pool

Abstract

Complete sequencing of 62 mitochondrial DNAs (mtDNAs) belonging (or very closely related) to haplogroup H revealed that this mtDNA haplogroup--by far the most common in Europe--is subdivided into numerous subhaplogroups, with at least 15 of them (H1-H15) identifiable by characteristic mutations. All the haplogroup H mtDNAs found in 5,743 subjects from 43 populations were then screened for diagnostic markers of subhaplogroups H1 and H3. This survey showed that both subhaplogroups display frequency peaks, centered in Iberia and surrounding areas, with distributions declining toward the northeast and southeast--a pattern extremely similar to that previously reported for mtDNA haplogroup V. Furthermore, the coalescence ages of H1 and H3 (~11,000 years) are close to that previously reported for V. These findings have major implications for the origin of Europeans, since they attest that the Franco-Cantabrian refuge area was indeed the source of late-glacial expansions of hunter-gatherers that repopulated much of Central and Northern Europe from ~15,000 years ago. This has also some implications for disease studies. For instance, the high occurrence of H1 and H3 in Iberia led us to re-evaluate the haplogroup distribution in 50 Spanish families affected by nonsyndromic sensorineural deafness due to the A1555G mutation. The survey revealed that the previously reported excess of H among these families is caused entirely by H3 and is due to a major, probably nonrecent, founder event.

Extensive and rapid screening for major mitochondrial DNA point mutations in patients with hereditary hearing loss

“…The m.8348A4G homoplasmic transition is one of the characteristic mtSNPs of mitochondrial haplogroup H1b, and the pathogenicity of this mutation still remains controversial. 41,42 The clinical course of this patient must therefore be followed closely and further detailed investigation is required.…”

Phylogeographic mitogenomics of Atlantic codGadus morhua: Variation in and among trans‐Atlantic, trans‐Laurentian, Northern cod, and landlocked fjord populations

“…The observed mean genetic distance of 0.039 substitutions per site then gives an estimated divergence rate of 1.03 × 10 −8 substitutions/site/year, and a temporal interval of 5,844 years between substitutions. These values are similar to those calculated by Carr and Marshall (2008a) for the 15,655‐bp cod genome without the control region, and only slightly higher than that calculated for the Alaska pollock (Carr & Marshall, 2008b) and Homo (Achilli et al., 2004). Similar results are obtained with Alaska pollock ( Gadus chalcogrammus ) as the outgroup (Lait, 2016).…”

Ancient mitochondrial lineages support the prehistoric maternal root of Basques in Northern Iberian Peninsula

“…Strikingly, with the exception of T2b, whose frequency peak is located in the North of Italy, 33 subhaplogroups H1 and U5b reach their highest frequencies in the North of the Iberian Peninsula, specifically in the region where the Franco-Cantabrian refuge was settled during the Upper Palaeolithic. 8,34,35 Two subhaplogroups found in Santimamiñe, U5a2a and U3a, are scarce in prehistoric remains and virtually absent in current European populations. However, these haplogroups of the samples S.12N and S.16G are of great interest because they are the most ancient evidence of the presence of subhaplogroups U5a2a and U3a found to date in Western Europe (Supplementary Appendix).…”

“…5,6 Based on genetic data of current populations, the Franco-Cantabrian region (south-western Europe) appears as a keystone in the post-glacial settlement of the European continent. 1,[7][8][9] Even though human remains of pre-Neolithic period are very scarce, archaeological data from this region, such as abundant cultural records of Palaeolithic hunter-gatherer human groups living during the Last Glacial Maximum, suggest that this was the most densely populated European region along the Upper Palaeolithic. 10 The Cave of Santimamiñe is located at the oriental side of the Oka river basin and very close to its estuary, o10 km from the current shore of Cantabrian sea, within the area of settlement of the FrancoCantabrian refuge ( Figure 1).…”