Monday, June 12, 2006

Distinguishing haplogroups from each other

Determining your haplogroup is not a streightforward task. There may also be some uncertainty connected to your reported haplogroup from the DNA testing lab. I have taken the liberty to repost parts of a letter originally written by DNA guru Prof. Bryan Sykes, Ph.D. In his letter, Dr. Sykes explains the process of distinguishing haplogroup U4 (Ulrike) from haplogroup H (Helena). As we learn more about these markers, we're better able to sort people into groupings. The letter is quite technical:

From: "Annie, The WritingTeacher"
Subject: [DNA] Letter to me from Bryan Sykes on distinguishing H from U4 with 356
Date: Thu, 05 Sep 2002 09:29:59 -0700

Dear Anne,

David tells me that on your original certificate, issued in August 2000, you were placed in the clan of Helena but that when you were sent a replacement you had become a daughter of Ulrike instead. Of course your actual DNA sequence hadn't changed, but the assignment of you clan had. It may help if I explain how that is done.

Clans are defined by a mixture of two sorts of genetic markers, the variants in the control region sequence and the variants at a number of other sites around the mtDNA molecule - now generally called SNPs (short for Single Nucleotide Polymorphisms). These are usually designated as +4643Rsa1 or +11329Alu1 etc as you have pointed out in your messages.
However, that would put the price to customers up hugely because each one of the SNPs had to be done separately - although I know that Oxford Ancestors are looking into offering this service.
But even that would not guarantee completely accurate assignment in every single case. Only sequencing the entire mtDNA circle of sixteen and a half thousand bases at astronomical cost would do that - though even that would not be any good unless you had at your fingertips a database of thousands of other complete sequences with which to compare it and only a handful have been completely sequenced to date. Also, as more work is reported, the evolutionary networks will change.

What I am getting at is that no system is foolproof. The Oxford Ancestors service, to keep it affordable, only sequences the control region. Then the sequence is compared to a database which holds other sequences which have been examined for SNP variants. If the customers control sequence matches up with one of these then it is assigned to the same clan. In other cases, where there is not an exact match, the database is searched for close matches or sites which are characteristic of particular clans. In the case of your sequence which has variants from the reference sequence at 189, 356, 362 (we delete the 16 prefix for HVS1) two of the three variants are quite unstable - that means they can mutate back and forth. Position 189 is one of the least stable of all and 362 is not very far behind. Position 356 is far more stable and is also characteristic of clade U4, whose clan mother is Ulrike. However, it is not completely stable and does crop up in other clans - one of which is Helena.

So the sequence 189, 356, 362 could be in the clan of Ulrike mutating at the unstable positions 189 and 362 away from the U4 root sequence of 356. Or it could be in the clan of Helena with a rare variant at 356 taking it away from 189, 362. One way of telling the two apart is to look at the variant at 073. This is actually in HVSII and not HVSI and that was a source of confusion in some of the email exchanges I have read. Oxford Ancestors doesn't do the 073 test, as you know, so the sequence was assigned on the balance of probabilities to Ulrike. I have now had a chance to compare the sequence to some new research data of my own from Britain in which we did do the 073 test and found five exact matches which carry A at 073, indicative of clade H. So I think you are probably correct and are indeed a daughter of Helena rather than Ulrike. This means that the mutation at 356 would have occurred on a Helena background rather than the 189 and 362 variants occurring on a Ulrike background.

That might explain why you were originally issued with a Helena certificate in August 2000. At that time, the service was being sent out from my laboratory before Oxford Ancestors acquired its own premises. That means that whoever did that first assignment, and it may well have been me, did recognize the ambiguous nature of the 356 mutation in that particular sequence but that piece of information was not properly transferred to the new set-up - and that is my fault.

I must thank you for clarifying the assignment of this particular sequence. It is a changing field and your observation has helped it move on one more stage further. I am sure Dr Ashworth will want to issue a new Helena certificate. And of course, I hope you are pleased to have moved back to your original clan.

Yours sincerely
Bryan Sykes MA PhD DSc
Professor of Human Genetics University of Oxford

Link to original Usenet posting.

Sunday, June 11, 2006

Test yourself for your deep maternal ancestry

Many services are now available US and Europe for mitochondrial DNA testing. Some of the services are listed here:

Family Tree DNA
National Geographic's Genographic Project
Oxford Ancestors

Read more about
DNA testing and Mitochondrial DNA (mtDNA) testing at Wikipedia.

Russian scientific article about the distribution of U4 amongst Eastern Europeans

Phylogenetic relationships between the sequences of the mitochondrial DNA (mtDNA) hypervariable segment 1, belonging to subhaplogroup U4, were examined in the populations of Eastern Europe, Ural, and Northwest Siberia. It was shown that the frequency of subhaplogroup U4, as well as its proportion in the U-component of the gene pools, increased eastwards, reaching maximum values in the populations of Northwest Siberia.

Phylogenetic analysis it was showed that the appearance of specific U4-lineage (16113C-16356-16362) in the ancestors of Mansi was most likely caused by its divergence from the East European cluster 16356-16362 in the Late Upper Paleolithic (18566 +/- 12915 years before present). Other U4 mtDNA lineages (16189-16356 and 16311-16356), typical mostly of the indigenous populations of Northwest Siberia (Mansi, Nganasans, and Kets) may have formed during the Neolithic-early Bronze Age (6055 +/- 3599 years before present, on average).

It seems likely that the isolation of ancient populations inhabiting the region between the Ob' and Yenisei rivers was the key factor, providing the appearance of the unique Caucasoid mtDNA lineages in their gene pools. These results were consistent with the traditional point of view on the mixed origin of the Finno-Ugric populations of the Volga-Ural region and West Siberia, resulted from the genetic relationships between the populations of Europe and Asia.

B. A. Malyarchuk, Differentiation of the Mitochondrial Subhaplogroup U4 in the Populations of Eastern Europe, Ural, and Western Siberia: Implication to the Genetic History of the Uralic Populations, Russian Journal of Genetics, Volume 40, Issue 11, Nov 2004, Pages 1281 - 1287, DOI 10.1023/B:RUGE.0000048671.32870.cb, URL

See also this reference.

Why the name Ulrike?

Ulrike's mother, Ursula, was introduced by Prof. Sykes in his book "The Seven Daughters of Eve" about late research that reveals our deep genetic ancestry. In this book he gives a first hand account of his research into mitochondrial DNA, which passes from generation to generation through the maternal line, allowing us to track our genetic ancestry through time and space. Prof. Sykes has found that almost all Europeans can trace their ancestry back to one of seven women, whom he named “The Seven Daughters of Eve”. Ursula was one of these women. In this book we learn where our ancient genetic ancestors lived and what their lives were like. “The Seven Daughters of Eve” does not only re-examine how we have evolved, but also gives us a new sense of individuality and identity.

Ulrike is not among the original “Seven Daughters of Eve” but rather a late decendant of Ursula. Infact Ursula lived about 45,000 years ago, or about 27,000 years before Ulrike. Today the subclan of Ulrike, with just under 2% of Europeans among its members, can claim to being included among the numerically important clans.

Ulrike may have lived about 18,000 years ago in the cold refuges of the Ukraine at the northern limits of human habitation. Though Ulrike’s descendants are nowhere common, the clan is found today mainly in the east and north of Europe with particularly high concentrations in Scandinavia and the Baltic states. Read more.

More scientifically speaking, the Ulrike clade is most often referred to as mtDNA haplogroup U4, a subgroup of haplogroup U. For an atlas of early human migrations, visit National Geographic.