As I mentioned in my newsletter, one of the DNA tests I took last year was a mitochondrial DNA test. Mitochondria (singular mitochondrion) are little organelles in every one of our cells. Some types of cells have only one mitochondrion, others have thousands. Mitochondria are often described as the power-houses of our cells because one of their main functions is generating energy for the cell, but they have several other functions too.
What makes mitochondria particularly interesting is that they carry their own DNA – usually denoted mtDNA – which is quite distinct from the DNA we normally hear about, the DNA in the cell’s nucleus. Moreover all our mitochondria are precise copies of the mitochondria in the fertilized egg which made us, which means they are identical to our mothers’ mitochondria. Consequently our mtDNA is identical to our mothers’ mtDNA. Sperm have the father’s mitochondria with his mtDNA in their tails, but the tails never enter the egg, so none of the father’s mitochondria or mtDNA gets passed on to the offspring.
The fact that only mothers pass on their mtDNA to their children has interesting implications: I got my mtDNA from my mother who in turn got hers from her mother, our grandma, Lizzie Walker née Shields. All my cousins got their mtDNA from the mothers who, in turn, got theirs from their mother, our grandma, Lizzie Walker née Shields. So if all 13 cousins got their mtDNA from our grandma, then all of us have identical mtDNA. So my mtDNA data will be their mtDNA data too.
Not only that, the female cousins will have passed that same mtDNA on to their children, and so on. It’s easy to map out who shares grandma’s mtDNA by simply bearing in mind that both males and females have their mother’s mtDNA, but only females pass that mtDNA on to their offspring. Here’s a tree showing who has inherited grandma’s mtDNA and will therefore have identical mtDNA to myself.
At every stage all the children of that ancestor inherited that same mtDNA and all the female children will have passed it on to their children, and so on. As it happens, Jane Ann Shields née Shevals only had two daughters, grandma and Aunt Cecilia, but Aunt Cecilia only had sons, so our mtDNA didn’t travelled any further down that line. Cecilia Pringle, on the other hand, has many descendants following all-female lines besides ourselves, and they all share or shared our mtDNA. Cecilia Brown had one daughter apart from Cecilia Pringle; that was Eleanor Lloyd, but I don’t know of any any descendants. Cecilia Rutherford only had the one daughter, our ancestor, Cecilia Brown.
So, of these recent ancestors in the all-female line, only Cecilia Pringle and our grandma seem to have passed their (and our) mtDNA down to people alive today, but if we could go back through further generations in this line we would certainly find many more who were prolific and who have passed their mtDNA down to the present day. In fact there are bound to be many hundreds of thousands of people alive today who share our mtDNA because their all-female line and ours meet at some point in the last few hundred years.
Uses of mtDNA results
Now that brings up the first potential use of my mtDNA results – finding some distant relations. The company I tested with – Family Tree DNA of Houston, Texas – automatically compared my mtDNA results with the results of everyone else who had taken the same test, and new testees are compared as and when their results are known. I also made separate searches on other public mtDNA databases. Through these comparisons I now know of 51 people with extremely close matches to our mtDNA, and I’ll be working with as many of them as are willing in an effort to establish just where our ancestral lines cross.
Unfortunately most of these people are in the USA and very few of them have traced their ancestry back to the UK in the all-female line. So, while we know that they are definitely relations – their all-female line and ours must meet at some point in the not-too-distant past – the chance of establishing just how we are related to them is probably small. The predominance of US-situated matches is really a consequence of the fact the most people who have taken mtDNA tests live in the USA. Nonetheless there are two of my close matches with known all-female lines leading to the UK (Scotland and Northern Ireland) where we may be able to find the connection to our family tree more easily. If only more people in the UK and Ireland would take this mtDNA test, we might find many equally, or even more, promising matches.
Incidentally the identities of both Richard III and Czar Nicholas II were confirmed by comparing mtDNA taken from their remains with mtDNA from known relations of their mothers in their all-female lines.
The second use of our mtDNA results is to establish our deep ancestral origins – the route that members of our all-female line followed from our earliest ancestors in Africa to Chopwell in 1910. Some of you may have watched a very recent TV programme where comedian, Eddie Izzard, not only established the route his all-female line had taken, he actually retraced that route on the ground.*
If we extend that “Source of our mtDNA” diagram above off to the left to Cecilia Rutherford’s mother, her mother, her mother’s mother and so on for another, say, 6,000 generations, we’ll reach a rather special lady. She lived in East Africa around 180,000 years ago, and she is generally known as “Mitochondrial Eve” because she was the source of the mtDNA in every human alive today – in other words if anybody in the world traced their all-female line back in time they would eventually reach this woman. Her proper description would be our Mitochondrial Most Recent Common Ancestor.
There were many other humans alive at the same time, and most of them will be our ancestors in other lines, but not in the all-female line, the line that provides our mtDNA. The mtDNA in all these other humans has died out – only Mitochondrial Eve passed her mtDNA to the present day.
I’ve stated that our mtDNA is identical to our mother’s, our mother’s mother’s and so on. Does this mean that out mtDNA is identical to Mitochondrial Eve’s. No, not quite, because very occasionally there were mutations – changes to the mtDNA. Some woman’s mtDNA was changed, perhaps because of naturally occurring radiation, perhaps because of exposure to certain chemicals, perhaps because of a simple copying error, and that changed the mtDNA which was passed to that woman’s children.
mtDNA controls the building and functioning of the mitochondria which are vital to the cell and indeed to the person carrying them. Some mutations produce non-functioning or badly functioning mitochondria with fatal results on the foetus or child, but many types of mutation do little or no damage and the mitochondria carrying it are sufficiently functional to allow the bearers to thrive and reproduce. Such mutations in the mtDNA of females would be passed on to her children and to all her descendants in all-female lines.
So, as our all-female line of ancestors made their way over the intervening millennia from Africa to Chopwell, they accumulated quite a number of these mutations, and scientists have figured out roughly when many of these mutations occurred. Many of the people carrying each mutation will have moved on to other areas, the biggest concentrations of people with a particular mutation will still be in the same general area where the mutation first occurred. This makes it possible to determine roughly where that particular mutation occurred.
Knowing roughly when and where each mutation occurred makes it possible to use our mutations to describe the approximate route and very approximate timings of our own ancestors’ ancient migrations. Let us have a closer look at mtDNA so we can better understand the science behind all this.
We can consider mtDNA as a sequence of 16,569 of the nucleic acids Adenine, Cytosine, Guanine and Thymine, normally abbreviated to their initial letters A, C, G and T. So the raw output of my mtDNA test is the full sequence of my 16,569 nucleic acids: GATCACAGGTCTATCACCC … TAAATAAGACATCACGATG. This is of limited value as it hides the interesting features – the mutations – in a featureless sea of results, so a much better format has been devised.
Scientists have reconstructed the nucleic acid sequence of the earliest humans – Mitochondrial Eve if you like. This is known as the Reconstructed Sapiens Reference Sequence or R.S.R.S. – and we simply list our mutations, the places where we are diufferent from that sequence. In most cases a mutation consists of the substitution of one nucleic acid for another. Such mutations are called Transitions or Transversions – for our purposes we don’t need to understand the difference between the two. For example, one of our mutations is the Transition T8468C which means that in position 8468 of the sequence, where the Reconstructed Sapiens Reference Sequence (R.S.R.S) has the nucleic acid Thymine (denoted T), we, instead, have Cytosine (denoted C). Where the second letter in a substitution-type mutation is shown lower-case, such as in our A825t – the substitution of Thymine for Adenine in position 825 of our sequence, it’s a Tranversion rather than a Transition. Tranversions are much rarer than Transitions.
Another type of mutation is called an Insertion. This means that there is an extra nucleic in our sequence which the R.S.R.S. doesn’t have. For example we have an Insertion denoted 315.1C which means we have an additional Cytosine after position 315 in the R.S.R.S. Where there are two consecutive Insertions, such as the extra A and C (Adenine and Cytosine) we have after position 522, it is denoted 522.1A, 522.2C.
Altogether our mtDNA has 57 mutations – 51 Transitions, 2 Transversions and 4 Insertions – which I’ve listed at the end of this article.
The final concept we need to understand before embarking on our imaginary journey is that of a “mitochondrial haplogroup” – mt haplogroup . A mt haplogroup is a group of people carrying the same set of mitochondrial mutations because they descend, in the all-female line, from the same person. As we’ll see, some 60,000 years ago our ancestors in the all-female line belonged to a mt haplogroup which scientists have designated “N”, because they all descended, in the all-female, line from the same female carrying a particular set of mutations. All the members of that haplogroup carried the same mitochondrial mutations.
For many, many generations, all the thousands of descendants in the all-female line of that woman continued to carry that same set of mutations – but very occasionally the mtDNA in one of the female members of that haplogroup would suffer one or more extra mutations. When that happened she founded a new haplogroup carrying all mt haplogroup N’s mutations plus her extra mutations. In that way members of mt haplogroup N founded mt haplogroups I, W, Y., A, S, X and R. The lady who founded mt haplogroup R was one of our ancestors, so from then on members of our all-female line were in mt haplogroup R until one member of that line had more mitochondrial mutations putting her descendants into a new haplogroup.
The Journey from Africa
Now we can look briefly at the migration routes our ancestors took from Africa to Chopwell. I won’t mention all the mt haplogroups we passed through, just a selection, but there’s a comprehensive list in the results below.
The descendants of Mitochondrial Eve spread out over Africa and eventually, about 70,000 years ago, one group, unromantically named mt haplogroup L3, were to be found in and around Ethiopia. This group is important to our story because some of this group, which included one or more generations of our all-female line, crossed the Red Sea into Arabia – modern-day Yemen to be precise.
By 60,000 years ago, our line had accumulated more mutations and belonged to mt haplogroup N. They lived in and around modern-day Israel. It is very likely that they co-existed there with Neanderthals at this time and there was some interbreeding – my ordinary DNA is 1.8% Neanderthal, and yours too will have a small amount of Neanderthal DNA. Some of their descendants, including members of our all-female line, began to explore surrounding areas.
By 55,000 years ago, we find our all-female line in modern-day Syria in mt haplogroup R. This further branched into other groups – in our line to mt haplogroup J about 35,000 years ago. You may remember that some years ago Professor Bryan Sykes of Oxford University, one of the pioneers of DNA testing, wrote a book entitled “The Seven Daughters of Eve” where he postulated that all modern-day westerners descend, in their all-female lines, from one of seven women. These actually corresponded to the originators of seven mt haplogroups, and he gave these imaginary ladies names beginning with their haplogroup letters. The originator of the mt haplogroup in our line, mt haplogroup J, was named Jasmine.
Sykes devotes a whole chapter to this imagined lady and it is well worth reading in its entirety if you get the opportunity, but I will summarize it here. Jasmine and her descendants were probably the first in our all-female line to live in permanent settlements. Although they still hunted – their settlements were on the annual migration route of Persian gazelles – and still collected wild nuts and seeds, it was this group which eventually perfected the basic techniques of farming.
Over the next several thousand years they gradually improved wild varieties of grain and other crops by artificial selection, and it was they who first domesticated goats and cattle for milk, meat and motive power. It wasn’t long before hunting and foraging were largely forgotten and everyone lived an agrarian lifestyle. By then, say 12,000 years ago, Jamine’s descendants occupied a large area in and around Syria, Turkey, Greece and beyond – the particular group that we descend from, designated mt haplogroup J1c, being largely in Greece.
Now Jasmine’s descendants, our ancestors included, were poised to spread farming throughout Europe. Some of them headed north-west, but our all-female line took a different route – westward along the Mediterranean coast, sometimes over land, sometimes by sea. They travelled Greece to Italy to Sardinia to Corsica to France to Spain. Coincidentally, around 5,000 years ago our all-female line had reached the area where Faye lives today, and doubtless many of their descendants are still in that area today.
Our all-female line had by then accumulated more mutations and formed a group classified as mt haplogroup J1c3b. Although this occurred in the Stone Age, this is still the mitochondrial haplogroup we belong to today.
Over the next 5,000 years our ancestral line moved slowly but surely onward. The Bronze Age, Iron Age, the Roman Occupation and the so-called Dark Ages came and went as our all-female ancestral line moved to Portugal, north by sea to Ireland and then over to Scotland. By the time of the Industrial Revolution they’d reached North Northumberland, and the 19th century drift from the land to industry and mining brought them down to Tyneside and Co Durham. One hundred years ago, Edward and Jane Ann Willis (née Shevals) brought their family, including grandma and Aunt Cecilia, to Chopwell.
Since our line incurred the mutation which defined us as belonging to mt haplogroup J1c3b, one of our mutations, G185A, has undone itself and reverted back to its original form. At some point we’ve also accumulated some extra mutations which aren’t part of our mt haplogroup definitions. Most of these are in positions which scientists tend to regard as unusable for various reasons, but one of our extra mutations, G7269A, might be significant. With our loss of mutation G185A and our addition of mutation G7269A, our mtDNA isn’t quite the same as other members of mt haplogroup J1c3b. Consequently we really belong to a new mt haplogroup but this has not yet been defined, probably because there are too few of us to warrant it. More on this in the results section.
From Chopwell the family spread out over the area and some travelled further carrying our mitochondrial DNA with them. Betty took it to London, Lynda to Bedford, Ann to Sussex, Faye back to Spain. Ian took our mtDNA even further afield, but sadly, like other males in the family, he can’t pass this particular genetic inheritance on to his offspring.
Before moving on to the actual details of our mtDNA, I’ll briefly touch on the medical implications of mutations in mtDNA. Some mutations increase or decrease the risk of certain medical conditions, but it’s a subject best avoided for many reasons which I’m sure I don’t need to enumerate. I will, however, mention one negative and one positive aspect of our mtDNA.
First the negative one. One of our mutations seems to show up in many of the victims of the Black Death, so perhaps that mutation makes its bearers particularly susceptible to that disease. So next time Bubonic Plague sweeps the country, we’ll have to watch out!
More happily it seems that our family can better survive a certain type of breast cancer than most people, because one or more of our mutations delays metastasis – the spread of the cancer – by a significant amount. I wonder if that played any part in Aunt Winnie’s full recovery from her breast cancer?
Here are the the actual results. First our mutations in numerical order – these are given in three ranges, which is the usual way of doing this. Again, for our purposes, the reasons for this are not particularly important, so I won’t attempt to explain why.
First mutations (differences from the Reconstructed Sapiens Reference Sequence – R.S.R.S.) in positions 1 to 574 of the sequence. This is known as HVR2 – HyperVariable Region 2.
C146T C152T C195T A247G C295T 309.1C 315.1C C462T T489C 522.1A 522.2C
Next mutations in positions 575 to 16000 of the R.S.R.S. This is known as the Control Region.
A769G A825t A1018G A2758G C2885T G3010A T3594C G4104A T4216C T4312C G7146A T7256C G7269A A7521G T8468C T8655C G8701A C9540T T10664C A10688G C10810T C10873T C10915T A11251G A11914G A12612G T12705C G13105A G13276A T13506C T13650C G13708A C13934T T14798C C15367T C15452a
Finally mutations in positions 16001 to 16569 of the R.S.R.S. This is known as HVR1 – HyperVariable Region 1.
C16069T T16126C A16129G T16187C C16189T T16223C G16230A T16278C C16311T C16519T
Next we’ll list our mutations in chronological order. Down the left-hand side of the table below I’ve listed the sequence of Haplogroups which our all-female line has belonged to over the millennia, and on the right I’ve shown the mutations which defined those haplogroups. As our ancestral line moved onward from Mitochondrial Eve it accumulated mutations, so as we move down the list of haplogroups the ancestors in that haplogroup had the defining mutations for that haplogroup and all the mutations for the haplogroups above it. By the time our line reached haplogroup we presently occupy – J1c3b – we had all the mutations shown in the table.
The exceptions are those mutations shown coloured green or red. The green ones were mutations present in one of our ancestral haplogroups, but somewhere down the line, that mutation has undone itself. This is known as a reverse mutation or reversion and is shown with an exclamation mark after it. For example one of the defining mutations in mt haplogroup N is G10398A, so at that stage members of our ancestral line carried that mutation. By the time members of our line were classified as mt haplogroup J, we have undergone the reversion A10398G! which means position 10398 in ourt sequence is back in the same state as the R.S.R.S., so the original mutation is cancelled out. Four such mutations/reversions in our line are shown here.
The mutation shown in red – G185A – is one which our ancestors in mt haplogroup J1c definitely carried, and the first of our ancestors to be classed as mt haplogroup J1c3b carried it too. The vast majority of people in Mitochondrial Haplogroup J1c3b still carry it, but we don’t. We must have undergone another reversion A185G! which is not, so, far defined. One day there may be a subgroup of mt haplogroup J1c3b for people like us who have lost mutation G185A.
[table]Haplogroup, Defining Mutations
mtMRCA,The most recent common mitochondrial ancestor of all mankind – Mitochondrial Eve
L1’2’3’4’5’6,C146T C182T T4312C T10664C C10915T A11914G G13276A G16230A
L2’3’4’5’6,C152T A2758G C2885T G7146A T8468C
L2’3’4’6, C195T A247G A825t T8655C A10688G C10810T G13105A T13506C G15301A A16129G T16187C C16189T
L3’4,T182C! T3594C T7256C T13650C T16278C
L3,A769G A1018G C16311T
N,G8701A C9540T G10398A C10873T A15301G!
JT,A11251G C15452a T16126C
J,C295T T489C A10398G! A12612G G13708A C16069T
J1c,G185A G228A T14798C
In addition to the defining mutations shown above, we also carry Transitions G7269A and C16519T and Insertions 309.1C, 315.1C, 522.1A and 522.2C. Scientists have deliberately avoided using these Insertions and the C16519T Transition in defining mt haplogroups because those mutations are known to be unreliable – they come and go far too readily to be usable. Transition G7269A, however, should be usable, so maybe it could join the reversion A185G!, mentioned above, in defining a future subgroup of mt haplogroup J1c3b for people such as ourselves. Maybe there’ll be an extra line in our table something like this.
[table]Haplogroup, Defining Mutations
??????, A185G! G7269A (Purely speculative.)[/table]
I hope this hasn’t bored you too much. If anyone has questions I’ll try to answer them (or find someone who can do so).
* “Meet the Izzards (1) – The Mum’s Line” BBC1 Wednesday 20 February 2013 21:00-22:00 Available on YouTube http://www.youtube.com/watch?v=BOXe3hcN3Eg