Are they related to me? I still don't know…When last I left you, I was searching for my great-great grandmother’s DNA in my own DNA.  Remember, legend has it she was Cherokee and I wanted to confirm the legend with a genetic test from a company called 23andMe.

In my last blog post, I showed how the two most powerful ancestry tests, mitochondrial DNA (mtDNA) and Y chromosome, were useless to me in my hunt. Now I want look at the rest of my DNA.  So here we go!

The Y chromosome and mtDNA are a small fraction of my DNA—something like 0.8% of the total DNA in one of my cells.  But they are incredibly useful because they change very little from generation to generation.  The mtDNA I got from my mom is probably exactly like hers.  Same with most of the Y I got from my dad.

The other 99.2% of my DNA is a lot trickier to look at from an ancestry perspective because it has changed a lot from generation to generation over time.  For example, the chromosomes I inherited from my parents are not the same as the ones they have.  I got a mix of their chromosomes

For example, my mom had two copies of chromosome 1 (and two copies of her other 22 chromosomes too).   As you know, she passed one chromosome 1 to me (my dad gave me my other one).  But, through a process called recombination, her two copies of chromosome 1 swapped DNA so that I got a hybrid of her two copies.  I inherited a unique chromosome never before seen.

This is all well and good from a survival of the species point of view, but it is a problem for ancestry testing.  Imagine that instead of my mom, we look at my Cherokee great-great grandmother.  She has just had a child who inherited a mix of her chromosome 1’s.  This chromosome will look Native American and the child would appear half Native American.

Actually, the test isn’t perfect yet and so there isn’t yet a “Native American” set per se.  Instead, here is how 23andMe describes Native American DNA in their tests:

“…people who identify themselves as Native American exhibit fairly consistent Ancestry Painting proportions of about 75% Asian and 25% European, plus or minus 10%.”

This means the chromosomes the child got from his or her mom won’t look Native American but instead will look 75% Asian and 25% European.  (See a realted post of mine elsewhere for why it looks like this.) Now imagine that this half Native American child grows up and has my grandfather as his or her son.

My grandpa will inherit a mix of his parents’ DNA too.  In this case the Native American DNA will mix with the European DNA to create a hybrid.  On average, you would now see something along the lines of 37.5% Asian (this is a simplification but it gets us into the ballpark of the number we might expect).

Each generation would see, on average, a continued dilution of this Asian part.  My dad would have 18% Asian, I would have 9%, etc.  Here are my ancestry results (click the image to enlarge):

Not a hint of Asian.  Looks like my great-great grandma wasn't Cherokee.  Or was she?

There are lots of ways she could still be Cherokee.  First off, I don’t know how solid the 75% number is for all Native Americans.  I don’t know how many Native Americans are in their database.  I also don’t know how much variation there will be tribe to tribe.

Secondly, you may have noticed that I was very careful to always say, “on average.”  This is because the recombinations don’t have to be a 50-50 swap.  It is true that if you look at a large number of recombination events, the average will be 50%.  But individual recombination events can be biased towards one or more chromosomes.  Occasionally you’ll get mostly one chromosome and sometimes mostly the other.

Sort of like flipping a coin—do it enough and you’ll get pretty close to half heads and half tails.  But if you flip a coin twice, you might get one head and one tail.  And you might not.  Half the time you’ll get two heads or two tails.

This is less a problem than you might think with our chromosomes since the recombination is spread over 23 pairs with each pair being independent of the others.  But it can still throw a monkey wrench into the works.  23andMe actually has a nice chart that hints at this by giving the most likely range of possibilities.  Unfortunately, this chart didn’t come up with my results and I had to stumble on it while I was playing around.

Using the chart, I can see that the bottom end of my expected results in 0.24% “Native American” (if I am reading the chart correctly).  That is pretty low and it seems like a pretty minor mistaken assumption at the beginning might knock this down to zero.

So where am I after this?  Still in the dark.  This is actually how many genetic tests end up.

The positive result tells you a lot.  Had there been Native American DNA, that would have been a slam dunk.  (This isn’t always the case with genetic tests but it would be here.)  But there wasn’t.  Which means, given that I was on the edge of detection, that she may or may not have been Cherokee.

Now, this isn’t 23andMe’s fault.  The test itself couldn’t be conclusive given how far back we need to go and the DNA tests that 23andMe offers.  In fact, 23andMe does an excellent job of presenting the data.  There are pretty chromosome paintings, graphs superimposed on world maps, etc.  All very nice.

I am still worried that the explanations that go along with these images assume an awful lot of knowledge that most people might not have.  Without that knowledge, it can be hard to assess the significance of a certain result.  Next blog that’ll become even more important as I tackle health conditions.

Genetic tests often don’t give as much information as you might think.In a previous blog I talked about getting my DNA tested with 23andMe.  Well, I got the email the other day saying that my results were ready.  So I logged on and up popped this screen pictured to the left.

All sorts of goodies to try out!  I feel like a kid at Christmas.

The first thing I thought I’d do is check out my ancestry.  My grandfather’s grandmother was supposedly Native American and so I wanted to find out if I could see that in my DNA.  (This relates to my supposed relationship with the outlaw Sam Starr but that is a different story.)

23andMe has this Native American testing app in their 23andMe Labs section.  I clicked on my data and up popped this result:

Recent Native American ancestry is unlikely

Has it all been lies?  My great, great grandma wasn’t Native American?  Not so fast…

A “no” answer on a genetics test doesn’t necessarily tell you a lot.  (And sometimes, the “yes” answer isn’t so helpful either!)   Now as a geneticist, I know the drawbacks of ancestry tests like these.  What I wanted to see was if 23andMe did a good job of explaining them.

I first checked out my mitochondrial DNA (mtDNA) and my Y chromosome data.  These DNA don’t change a lot from generation to generation and so are really good at tracing ancestry many generations back.  Their downside for me is how they are passed down.

The Y chromosome passes from father to sons.  My great, great grandma didn’t have a Y to pass on so of course my Y chromosome data wouldn’t show that she was Native American.

mtDNA passes from mom to her children.  At first this sounds promising since we are talking about my great, great grandma until we realize that I am related to this woman through my grandfather.  His mtDNA died with him (except for his female relatives and their descendants) so that is lost to me as well.

Here is what 23andMe has written under interpretation of my mtDNA and Y chromosome results:

This mitochondrial DNA haplogroup is inconsistent with Native American ancestry along the maternal (mother's mother's mother's …) line.

This Y chromosome haplogroup is inconsistent with Native American ancestry along the paternal (father's father's father's …) line.

I suppose this says what I just said but I am not sure how many people would really appreciate the limitations of mtDNA and Y chromosome data from this explanation.  There wasn’t a link to a more explicit discussion of the limitations of this sort of testing and there wasn’t anything I could see from a quick glance at the ancestry part of the site either.  An explicit explanation would be good or maybe a figure like this one:

To me, this drives home the point that there is a whole lot of missing ancestry.  It might help if they had some sort of family tree app where you could indicate as much as you know about family relationships.  Once you’ve inputted the data, it would spit out what tests results would be useful to look at.

So the mtDNA and Y chromosome test results are of little use to me in this quest.  (And of little use to me in general as it confirms my pasty whiteness.)  Next blog I’ll deal with the rest of my DNA and what that can and can’t tell me about my great, great grandma.

This photomicrograph shows Cyanobacteria (green) found
in a common pond. Image source: Wayne LanierLast blog I talked about mitochondria. These are the parts of a cell that ultimately turn our food into energy. They also have a very interesting past.

A billion years ago or so, mitochondria were free living bacteria. Then our ancestors hijacked them and now they do our bidding. And mitochondria aren't the only cells that got hijacked. So did the chloroplast’s ancestors.

Chloroplasts are the part of a plant cell that turns sunshine into sugar. Every green plant that we’ve looked at has them. And chloroplasts were almost certainly once free living cyanobacteria.

Both mitochondria and chloroplasts still have many bacterial qualities including having their own DNA. But they don't have a lot of their old DNA left. Most of it has migrated to where the rest of our DNA is kept—the nucleus. Or at least that's the theory.

Do scientists have any proof that DNA can move in a cell from compartment to compartment? As a matter of fact they do. At least with the chloroplast.

Scientists used their ability to put DNA specifically into a chloroplast or mitochondrion to design an experiment to look for cells where DNA had migrated. What they did was put some DNA into a chloroplast that could only be read in the nucleus. (Remember, chloroplasts and mitochondria are different enough that nuclear DNA doesn't work there and vice versa.)

The DNA they put in made the plant resistant to a poison IF the DNA could be read. One way the plant could survive was if the DNA they put in the chloroplast ended up moving from there to the nucleus. And it did.

In fact, it was pretty common in their experiment. The DNA moved in something like 1 in 16,000 pollen cells. A rate like this suggests that, for example, different cells on the same leaf might have different amounts of chloroplast DNA in their nuclei.

So DNA can move from the chloroplast to the nucleus. And probably from the mitochondrion to the nucleus too. The evidence is less direct for this but there is plenty of DNA in the nuclei of lots of different plants and animals that looks very mitochondrion-like.

This all fits in with our understanding that DNA is not as stable as a lot of people think. DNA changes between generations and within an organism. Chromosomes can get rearranged, genes copied or deleted, small DNA changes can happen and who knows what else. And these changes are a big part of the motor that drives evolution.

This former free living bacterium now supplies our cells
their energy.Current theories hold that life began on Earth around 3.5 billion years ago. About a billion years ago, a single celled beast engulfed and absorbed another single celled creature. We are all descended from that hijacking.

The hijacked cell has over time become the mitochondrion. This organelle is responsible for making our energy. But it still has the marks of having once been a free living bacterium.

First off, mitochondria still have remnants of their old DNA. There isn’t much there in human mitochondria but there is enough to still get us into trouble. A big part of aging might be due to damage to this mitochondrial DNA (mtDNA). Some genetic diseases are also caused by mutations in mtDNA.

The DNA in mitochondria is also much more like bacterial DNA compared to the rest of our DNA. In fact, the mitochondrion has its own bacteria-like machinery for reading its DNA. This means that mitochondria can’t read the genes in our nucleus and vice versa. Mitochondria are so similar to bacteria that some antibiotics can damage them too.

Even though it was once free living, the mitochondrion doesn’t have a lot of its original DNA left. Over time, most of our mitochondrion’s original genes have traveled to the nucleus. These genes now work in the nucleus to make most of a mitochondrion’s proteins which are then transported back to the mitochondrion.

After all these years, human mtDNA is now only around 16,000 bases long and has only 37 genes left. This is a far cry from even the simplest of bacteria, Mycoplasma genitalium, with its 582,970 bases and 521 genes.

Humans are not unique in having mitochondria. Every plant, animal, and fungus cell in the world that has been looked at has mitochondria. But the DNA in these mitochondria is all wildly different.

The size of mtDNA can range from just 6000 base pairs all the way up to 2 million base pairs. Sometimes the mtDNA is a circle like ours. Sometimes it is spread out over lots of little circles. Sometimes it is one long, linear piece of DNA. Sometimes it is lots and lots of little pieces of linear DNA. And sometimes it is too weird to describe in a short blog like this.

Mitochondria from different species also have different numbers of genes. Some species have mitochondria with nearly 100 genes. While others have as few as 5.

With up to 2000 mitochondria/cell, evolution has had a free hand in tinkering with mtDNA. If a mutation or change in mtDNA causes a problem, that mitochondrion simply goes away. If there is some advantage to the new DNA structure, it is free to sweep through and take over. It is amazing what evolution has done to this bacterium!

Of course, evolution has made the mitochondrion a shell of what it once was. But we could argue that it is one of the most successful beasts ever.

It has gone from humble bacterium to being part of every eukaryote in the world. If humans die out, mitochondria will still be around somewhere else. Mitochondria will outlive us all.

More information on mitochondrial genomes: http://dx.doi.org/10.1016/j.tig.2003.10.012