Sephardic signature within mtDNA haplogroup T (?)

This paper proposes that "The haplotype of a suspected Sephardic origin has mutations 16114T-16126T-16153A-16192T-16294T-16519C in the first control region of mito-
chondrial DNA."

From the paper:

four avenues are pursued: (1) A search is conducted throughout multiple databases of the first control region of mitochondrial DNA for the T2e5 motif to ascertain the prevalence and geographic affiliation of the new haplotype. (2) One T2e5 sample is
sequenced for polymorphisms along the entire mitochondrial DNA and compared with T2e sequences to identify any potential coding region mutations that are important for the Sephardic sequence and its relation to other branches. (3) A phylogenetic tree is built from T2e control sequences to provide further information on the relation among lineages including the Sephardic cluster. Although full genomic sequences are usually preferable to avoid misclassifications based on control region information alone, T2e is an ideal subhaplogroup to exploit the more abundant control region data because it is defined by mutations in the control regions alone. Time to the most recent common ancestor is estimated to address questions of when the lineage emerged as well as where. (4) The frequencies of T sub-haplogroups are compared across growing published literature of various populations including from Europe, the Americas, and the Near East. Although the geographic distribution of haplogroup T has been investigated, less is known about the different subhaplogroups, especially T2e.

With respect to (1), the author writes:

The combined databases do not appear to have any biases for Iberia, Mexico, or Sephardim.

This is a rather weak claim, since the incidence of a haplotype in a given dataset depends on the relative number of samples of the different populations, and Sephardic Jews are indeed over-represented in the database searches relative to their actual population numbers. In any case, no explicit test of bias was performed

Stronger evidence for the Sephardic-ness of the haplotype in question could be arrived by dating it to a period consistent with the origins of that population. However:

Time estimates to the most recent common ancestor of the Sephardic signature T2e5 ranged all the way from after the expulsion – clearly impossible – to 415 000 years before present (YBP) (Fast: 338 YBP, 95% confidence interval (95% CI)=present to 763 YBP; Intermediate: 688 YBP, 95% CI=present-3820 YBP; slow: 6811 YBP, CI1=present to 15 245). Given mutations rates that vary by two orders of magnitude,22 as well as other issues with mutation rates and the rho statistic,23,41 at present coalescence analysis cannot be used to distinguish between different plausible timelines for the proposed Sephardic cluster.

The third piece of evidence in favor of the hypothesis of this paper is the relative frequency of the parent haplogroup T2e relative to T2b. This is, however, irrelevant, since mtDNA haplogroup T2e has been found in prehistoric European hunter-gatherers, so- its higher frequency in Saudi Arabia today does not indicate that its presence in Europe was effected in historical times, e.g., by Jews.

Moreover, higher frequency -in itself- does not indicate the direction of gene flow. Suppose that a particular haplogroup occurs at a frequency of 50% in a population A of 10 million that lives 2,000 miles away, and at a frequency of 10% in a population B of 500 million that lives 500 miles away. Clearly, population B is a much better source of the haplogroup than A, despite its lower frequency.

The final piece of evidence produced by the author:

The small T2e5 cluster satisfies criteria for being a signature. Although it is premature to set specific thresholds of a signature, a sample of 25% known Sephardic and 50% suspicion of Sephardic origin is overwhelmingly above what would be expected for a general European haplogroup.

On the contrary, T2e5 is found in Latin America (including Brazil), Iberia, and among Sephardic Jews who trace their ancestry to Iberia. Hence, if there is anything "in common" between the current T2e5 population, it is the geographical background of Iberia.

Strong evidence for the specific Jewish origin of T2e5 would be provided if it turned up in a different Jewish population. In that case, it could be well argued that this was indeed a lineage of Jewish origin that happened (for whatever reason) to become more frequent in the Sephardic population. On the contrary, the absence of T2e5 in non-Sephardic Jews suggests that this is not necessarily a Jewish-origin lineage.

In conclusion: this paper represents a valiant attempt to identify a Sephardic signature, but I remain unconvinced that a strong enough case for T2e5 being such a signature has been made. The evidence appears to be consistent with that hypothesis, but not sufficient to reject alternatives, namely that this is represents a European founder in the Sephardic population. Indeed, the author honestly admits that the origin of the "Sephardic signature" remains elusive:

These include Jewish settlers seeking asylum after destruction of temples in Jerusalem by Romans and Babylonians 2000–2500 years ago, slightly earlier Jewish settlers in Iberia,7,43 non-Jewish Muslims in the dispersal of Islam 1000+ years ago, non-Jewish Iberian peopling 2500+ years ago that predates all Jewish influx,44 and settlers in Iberia (or Italy) 45000 years ago that entirely predate the existence of Jewish groups. Thus, what is arguably the most contentious issue of whether there is genetic evidence of original Jewish DNA for the Sephardic line cannot be resolved.

Does it matter whether the line was originally Jewish or not? Not in the grand scheme of things, but it is certainly important for geneaologists: if it was originally Jewish then e.g., Latin Americans who belong to it must seek Sephardic Jewish ancestors; if it was pre-Jewish Iberian, then they may/may not have such ancestors.

PS: A minor mistake in the paper is the identification of a Sephardic sample as coming from "Salonica, Turkey". Salonica has, of course, never been part of Turkey: it was part of the Ottoman Empire and is now part of Greece. Fortunately Salonica is prominent enough to avoid confusion, but it's always a good idea to use appropriate terminology when referring to placenames.

European Journal of Human Genetics advance online publication 23 November 2011; doi: 10.1038/ejhg.2011.200

Sephardic signature in haplogroup T mitochondrial DNA

Felice L Bedford

Abstract
A rare combination of mutations within mitochondrial DNA subhaplogroup T2e is identified as affiliated with Sephardic Jews, a group that has received relatively little attention. Four investigations were pursued: Search of the motif in 250 000 control region records across 8 databases, comparison of frequencies of T subhaplogroups (T1, T2b, T2c, T2e, T4, T*) across 11 diverse populations, creation of a phylogenic median-joining network from public T2e control region entries, and analysis of one Sephardic mitochondrial full genomic sequence with the motif. It was found that the rare motif belonged only to Sephardic descendents (Turkey, Bulgaria), to inhabitants of North American regions known for secret Spanish–Jewish colonization, or were consistent with Sephardic ancestry. The incidence of subhaplogroup T2e decreased from the Western Arabian Peninsula to Italy to Spain and into Western Europe. The ratio of sister subhaplogroups T2e to T2b was found to vary 40-fold across populations from a low in the British Isles to a high in Saudi Arabia with the ratio in Sephardim more similar to Saudi Arabia, Egypt, and Italy than to hosts Spain and Portugal. Coding region mutations of 2308G and 14499T may locate the Sephardic signature within T2e, but additional samples and reworking of current T2e phylogenetic branch structure is needed. The Sephardic Turkish community has a less pronounced founder effect than some Ashkenazi groups considered singly (eg, Polish), but other comparisons of interest await comparable averaging. Registries of signatures will benefit the study of populations with a large number of smaller-size founders.

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