WHAT IS DNA RECOMBINATION?

Recombination is another major source of genetic variation Each of us has a mixture of genetic material from our parents. The mixing of this genetic material occurs during recombination when homologous DNA strands align and cross over. Recombination effectively ‘shuffles’ maternal and paternal DNA, creating new combinations of variants in the daughter germ-cells (Figure 2).

Figure 2 Recombination contributes to human genetic variation by shuffling parental DNA and creating new combinations of variants. Image source: Creation Wiki.

What are the 3 methods of genetic recombination?

Three recombination techniques: transduction, transformation, and conjugation.

 

What is an example of genetic recombination?

Genetic recombination occurs naturally in meiosis. Recombination is also observed in mitosis, but it doesn’t occur as often in mitosis as it does in meiosis.

 

Why is DNA recombination important?

Recombinant DNA technology has also proven important to the production of vaccines and protein therapies such as human insulin, interferon, and human growth hormone. It is also used to produce clotting factors for treating hemophilia and in the development of gene therapy.

 

What Are Mutations?

Mutations are the original source of genetic variation. A mutation is a permanent alteration to a DNA sequence. De novo (new) mutations occur when there is an error during DNA replication that is not corrected by DNA repair enzymes. It is only once the error is copied by DNA replication, and fixed in the DNA that it is considered to be a mutation (Figure 1). Mutations may be beneficial to the organism; deleterious (harmful) to the organism; or neutral (have no effect on the fitness of the organism).

Somatic mutations can accumulate in our cells and are mostly harmless. They can lead to local changes in tissues such as moles appearing on the skin, and can also have more serious effects – for example leading to cancer.  To learn more about the role of somatic mutations in cancer have a look at this paper by Martincorena and Campbell¹. In this course we focus on heritable genetic variation, i.e. variation that occurs in germ cells.

(http://evolution.berkeley.edu/evolibrary/article/evo_20².)

There are three types of DNA Mutations:

A. Base substitution

1. Transition: this occurs when a purine is substituted with another purine or when a pyrimidine is substituted with another pyrimidine.
2. Transversion: when a purine is substituted for a pyrimidine or a pyrimidine replaces a purine.

B. Deletion

A deletion, resulting in a frameshift, results when one or more base pairs are lost from the DNA

C. Insertion

The insertion of additional base pairs may lead to frameshifts depending on whether or not multiples of three base pairs are inserted. Combinations of insertions and deletions leading to a variety of outcomes are also possible.

 What are the Causes of Mutations?

• Errors in DNA Replication

On very, very rare occasions DNA polymerase will incorporate a noncomplementary base into the daughter strand. During the next round of replication, the miss incorporated base would lead to a mutation. This, however, is very rare as the exonuclease functions as a proofreading mechanism recognizing mismatched base pairs and excising them.

• Errors in DNA Recombination

DNA often rearranges itself by a process called recombination which proceeds via a variety of mechanisms. Occasionally DNA is lost during replication leading to a mutation.

• Chemical Damage to DNA

Many chemical mutagens, some exogenous, some man-made, some environmental, are capable of damaging DNA. Many chemotherapeutic drugs and intercalating agent drugs function by damaging DNA.

• Radiation

Gamma rays, X-rays, even UV light can interact with compounds in the cell generating free radicals that cause chemical damage to DNA.

Genetic Testing

DNA is often found in human fingerprints. But because there is so little of it there, scientists often need to turn to a certain kind of DNA—mitochondrial DNA (mtDNA).

While mtDNA can’t uniquely identify a human being, it can still help. For example, police can use this DNA to rule out suspects.

Fingerprint Patterns

Before going into why fingerprints have DNA, let’s go over what fingerprints are.

Fingerprints are markings left by the ridges on our fingers. Because fingerprint patterns are unique to each person, they can help us identify someone. For example, police often collect fingerprints from a crime scene to identify suspects or victims.

Fingerprints can be made in three different ways.

First, there are “plastic” fingerprints, which are physical indentations. They are left on soft surfaces like wet paint.

Second, there are “patent” fingerprints, which are also easy to see. They form when things like blood or dirt move from the finger to a hard surface.

Finally, there are “latent” fingerprints, which are invisible to the human eye. “Latent” fingerprints form when natural oils from the finger are transferred to a surface. To see “latent” fingerprints, additional processing steps like dusting are needed.

DNA in Fingerprints

So fingerprints have a visual pattern that helps us identify people. But fingerprints can also help us identify people in another way.

We are constantly shedding skin cells and leaving them behind when we touch things. This means fingerprints often have cells in them.

Our cells have DNA, much of which is unique to each person. This means we might be able to use DNA to identify people when the fingerprint patterns are too blurry.

But to get DNA, we must first get enough cells from the fingerprint and a lot of the time there aren’t many there. Luckily there are ways to get enough DNA from even a few cells.

DNA Profiling

After the police get DNA from a crime scene, they use a process called DNA profiling to identify people.

First, they use a method called PCR to make more copies of the DNA. Next, they can look at spots in the DNA that tend to be different between people. If someone shares a lot of the same spots with the DNA at a crime scene, then chances are good that person was there.

Here is where we run into a problem with DNA from fingerprints. Normally, the locations we look at are found in nuclear DNA (nuDNA). This is the DNA that give us our eye color, hair color and almost everything else about ourselves.

As you can guess, your nuDNA is very different from mine.  In fact, everyone’s nuDNA is different (well, except maybe identical twins).

The same is not true for the mitochondrial DNA (mtDNA) the police can get from fingerprints. Many relatives, even distant ones, pretty much share the same mtDNA. Which means you can’t uniquely identify someone as the criminal.

So why even use mtDNA? Because there is a lot more of it in a cell than there is nuDNA. Which means you can use it even when there are very few cells to test.

In each cell, there are only two copies of nuDNA, one from mom and one from dad. But there are hundreds or thousands of copies of mtDNA in each cell. Even if there are few cells or the DNA is degraded and hard to read, we can probably still use the mtDNA.

And mtDNA isn’t totally useless. It can still give evidence that someone could be a criminal.  If the crime scene mtDNA matches a suspect, then it might have come from the suspect. But it might have also come from one of the many people who share his or her mtDNA.

But where mtDNA really shines is in ruling someone out. If the mtDNA found at a crime scene doesn’t match a suspect’s mtDNA, then we know the crime scene DNA didn’t come from that suspect.

So if nuDNA is unique, why isn’t mtDNA? It comes down to how each one is passed down.

Nuclear DNA

Each cell has a single nucleus, which has nuclear DNA (nuDNA). NuDNA is organized in structures called chromosomes.

In total, we have 23 pairs of chromosomes, for a total of 46. One from each pair comes from mom and the other from dad. This is why, for the most part, we have two copies of each bit of our nuDNA.

Let’s focus on chromosome 1 (chr1) pair. Dad actually passes on a mix of his two chr1’s through a random mixing process called recombination. So does mom. This means the child gets a unique chr1 from dad and a unique chr1 from mom.

The same mixing process happens for the other chromosomes as well. This is what makes nuDNA unique and useful for identifying people.

Mitochondrial DNA

With mtDNA, things work differently. This DNA is found in mitochondria, which make energy for the cell.

Each cell has hundreds or thousands of mitochondria. That means there are lots of copies of mtDNA in each cell.

Also, mtDNA is not a mix of both parents’ DNA. Instead, you get all of your mtDNA from your mom, who got it from her mom, and so on like so:

(Image: Understanding Evolution)

When mtDNA is passed down from mother to child, it doesn’t change much. Over many generations, changes to the mtDNA can happen. But if two people are closely related through their maternal ancestors, they will have very similar or even identical mtDNA.

If two brothers are both suspects in a crime, their mtDNA may be the same. Only the nuDNA would be unique to each brother.

So there you have it. Fingerprints can have DNA in them but there is often so little you can only look at the mtDNA which is not unique.

By Siming Zhang, Stanford University

If you’re a book lover, you need to join Bookstagram

I’ve long known that people in the book community are amazing, but talking to a group of bookstagram pros showed me just how amazing they really are.

Bookstagram — for “book Instagram” — is a community of book lovers who come together on Instagram to showcase their love of the written word and storytelling through books. It’s a fascinating world, one I briefly tried to join (#selfieswithbooks was my “thing”), but ultimately I don’t have the artistic flourish to really be good at it.

There are those who are just amazing, though. I follow one person, @ursula_uriarte, who has almost 80k followers, a streamlined aesthetic, and an ability to take artistic photos of books that just blows my mind.

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A post shared by Ursula (@ursula_uriarte)

Bookstagrammers, as they’re called, are fun to follow if you’re into reading because not only is it thrilling to see your favorite books showcased on someone’s feed, but sometimes you get recommendations for the best books.

Amanda Gray Williams, whose bookstagram handle is @inagrayarea, said she started her bookstagram a few years back when “I didn’t have a lot of IRL friends who were big readers, and I thought it would be a great place to share my recommendations and just get to talk about books.

“The biggest draw now is that there is a built-in community, and it feels like a really safe space,” Williams added.

Karissa Riffel, of @karissariffel.books, said she loves the community; in fact, the great community completely changed her experience on bookstagram from when she first joined.

“I started out wanting to reach people who would be future readers of my books,” Riffel said, “but I found such a positive and vibrant community that, instead of a means to an end, my Bookstagram has become an end in and of itself.”

The sentiment about bookstagram’s community was echoed by Bree Buonomo of @livinginabookishfantasy, who said she made a friend she speaks with almost daily who lives in Puerto Rico, whom she never would have met without this medium.

Buonomo also noted there are some fun perks that come with being a bookstagrammer, “like receiving advanced reader copies (ARCs) of upcoming novels, getting requests to beta read, and receiving products to review, which I’ve loved doing each time the opportunity has been given!”

Bookstagram is fun to follow because it’s just cool to be surrounded by fellow book nerds, people who grew up and didn’t grow out of wanting to lose themselves into fictional worlds and don’t find it weird to love spending hours staring at an immobile piece of paper.

One thing that’s always struck me about the platform is just everyone’s artistry on display. I’m a big believer that there are myriad ways to be artistic and each one is as valid as the next. Being artistic in a bookstagram way requires having an eye for what colors and patterns and props look good with a book, as well as taking time to make sure the picture comes outright.

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A post shared by Amanda Gray Williams (@amandawilliamsbooks)

That was always my downfall on bookstagram: I’m too impatient! I would snap a few photos and then get bored and just call it a day. This is why I don’t consider myself a bookstagrammer; I’m more of a dabbler.

Bookstagram is great for authors as well, as having photos of their books shared increases visibility about their work.

Williams mentioned she loves to shout out books she’s adored, saying, “I have so many people message me about books they read because of my recommendations, and I can’t think of anything better!”

Ultimately bookstagram is about community and about celebrating books, something I, as an avid reader and aspiring author, think we can never have enough of in the world.

Repost

By Karis Rogerson

What makes the mitochondrial DNA special?

The transfer of mitochondrial DNA is a constantly changing process that results in the reception of maternal mitochondrial DNA by the offspring. Mitochondrial DNA contains 37 genes that occur only in the mitochondria. While this is a small number compared to the 20,000 genes found in the human genome, the mitochondrial genes come only from the female parent. Different populations show variations in their mitochondrial DNA, just as with the rest of the DNA inside the nucleus.

Mitochondrial DNA exists as multiple copies within each cell as there are several mitochondria per cell. This DNA is unique in that it doesn’t show any recombinant changes during its transmission through the generations. In the nucleus of the reproductive cells, in contrast, the DNA undergoes recombination to produce a new and essentially different copy of the parent’s genome, which is thereafter part of the child’s DNA.

However, mitochondrial DNA does undergo mutation, which is thought to be responsible for the inter-population variants of this genetic material. However, within the same person, all mitochondrial DNA molecules are largely identical and come from copies of the original copy of the mother’s mitochondrial genes present in the embryo.

How is mitochondrial DNA transferred to the offspring?

The experiments were carried out in experimental mice that had two different copies of mitochondrial DNA within each cell within two types of mitochondria. This could be an inheritable situation. The team showed that if there were two or more types of mitochondrial DNA in the mother’s cells, the transfer was regulated in two ways.

The first pathway was operative during egg development, while the second occurred during the period when the first few cells developed into an embryo. The two mechanisms of regulation ensure that different types of mitochondrial DNA do not occur in the same individual, a phenomenon called heteroplasmy. In such cases, the mitochondria cannot function normally.

Heteroplasmy is known to exist in nature, but as already stated, two distinct mechanisms oppose it. In the experimental setup, the production of more egg cells or oocytes is a low throughput process, and this in itself reduces the chances of heteroplasmy. One of the mitochondrial variants only was picked up during the process of oocyte maturation.

Moreover, following fertilization and once the oocyte began to develop into an embryo, the father’s mitochondrial DNA is actively broken down, ensuring that no cells thereafter carry this genetic material.

However, modern medical therapies, notably mitochondrial replacement, can result in low levels of heteroplasmy, which is shown to be more frequent in patient populations than was considered the case till now. This type of treatment is designed to stop disease-associated mitochondrial DNA from being transmitted to the child.

The female parent’s mitochondria are, in this case, replaced by those from a healthy individual. Such children are called the “children of three parents” but the technology should not be taken lightly, say the researchers. They stress the need to understand why variability in the mitochondrial DNA is required for the body’s normal functioning. Moreover, embryonic cells show an alteration in metabolism when heteroplasmy is present, which results in the formation of a higher concentration of reactive oxygen species. The consequence is that the inner mitochondrial membrane, which carries many enzymes involved in cell respiration and energy production and storage, can become deformed.

A Chart of yDNA and mtDNA from your Ancestors

The information on this page is meant to provide a very simple explanation of your Y-DNA and mtDNA Ancestry used for genealogical purposes. Scientists estimate that the total amount of Y-DNA of a man is less than 1% and the total amount of mtDNA in either a man or a woman is less than 1%. It is important to understand that after taking a Y-DNA and an mtDNA test, the majority of everyone’s DNA remains untested and it is called Autosomal DNA, with another 5% of a female’s DNA or 2 1/2% of a male’s DNA being x-chromosomal DNA. In a man this would mean roughly 95.5% of his DNA is Autosomal and in a woman, that figure would be roughly 94%

The two basic tests used for genealogy purposes are Y-DNA tests (male) and mtDNA tests (female). Both tests, the Y-DNA and the mtDNA, sample a very small amount of your total DNA and as genetic genealogists know, the test most is taken is for Y-DNA. It can show a relationship between two males; a genetic cousin is a term that is commonly used. The mtDNA test is less practical for genealogical use because traditionally the female’s birth or maiden name changes from generation to generation. With that said, mtDNA still may be used to prove scientifically that two people (male or female) share a common maternal ancestor, although it is more effective at proving two people do not share a common maternal ancestor.

Below is a simple chart showing two children, a brother, and a sister. In addition to them, their parents, grandparents, great grandparents and gg grandparents are also shown for visualization of their DNA Ancestry. Note how the brother has a two-color graphic to show how he carries both Y-DNA and mtDNA. The brother’s sister has a one-color graphic; this is to show that she only carries mtDNA.

For the purposes of our Phillips DNA study, a male DNA participant who tests both Y-DNA and mtDNA will have two EKA’s (Earliest Known Ancestors). One will be a paternal ancestor (straight line father’s Y-DNA) and the other a maternal ancestor (straight line mother’s mtDNA).

Since women do not have Y-DNA, a female will only have one EKA that is associated with her DNA test, her maternal ancestor (straight line mother’s mtDNA). See the chart below to help visualize the Y-DNA and mtDNA Ancestry of the two test participants, the previously mentioned brother and sister.

Please note that there are many other lines of DNA that remain untested even if you have tested both your Y-DNA and your mtDNA. These untested DNA lines are represented below by the circles and boxes that have no interior color, they are your autosomal DNA. Genetic scientists are slowly developing tests that can study and classify your autosomal DNA, but these tests are much more expensive, controversial, complicated and less straight forward than the Y-DNA test or the mtDNA test.

Ancestry Chart of Inherited Paternal Y-DNA and Maternal mtDNA (Fig. 1)

 

Details of Inheritance

Simplified Chart showing the less than 1% of Y-DNA and/or mtDNA in a brother and a sister. (Fig. 2)

As you can see from figure 1 and 2, a son inherits the Y-DNA of his father and the mtDNA of his mother. A daughter inherits the mtDNA of her mother but not the Y-DNA of her father. Because of a male’s inheritance of both Y-DNA and mtDNA, a male may be tested for both his father’s Y-DNA and his mother’s mtDNA. A female may only test for her mtDNA because she has no Y-DNA from her father.

Even though the male may test both Y-DNA and mtDNA, he cannot pass his mother’s mtDNA to his children. However, he will pass down his father’s Y-DNA to his sons. A female will only pass down her mother’s mtDNA, whether it be to her sons or her daughters.

Simplified Chart showing less than 1% of Y-DNA or mtDNA passed down to children from their parents. (Fig. 3)

Figure 3 is a sibling chart of the Y-DNA and mtDNA a brother will pass down to his children and a similar chart for the mtDNA a sister will pass down to her children.

When the brother starts having children, as stated above, he will pass his father’s Y-DNA on to his sons, who will likewise do so to their sons. Even though he has his mother’s mtDNA, he cannot pass her mtDNA on to his daughters. The mother of his children will pass her own mother’s mtDNA on to their children, both their sons and their daughters.

When the sister starts having children, she will pass her mother’s mtDNA on to her daughters, who will likewise do so to their daughters. She will also pass her mtDNA down to her sons, but as stated above, her sons cannot pass her mtDNA on to their children. She cannot pass down her father’s Y-DNA to her children because she has no Y-DNA. The father of her children will pass his Y-DNA to her sons.

Y-DNA Lineages and mtDNA Lineages

Most genealogists should focus on a Y-DNA Lineage when researching a family surname. The surname lineages are commonly written like this:

1. John Phillips b. 1756 VA m. Mary Smith
2. Thomas Phillips b. 1783 TN m. Polly Jones b. 1785
3. Henry Phillips b. 1809 TN m. Sarah Redmond b. 1811 TN
4. John Phillips b. 1831 KY m. 2nd Olivia White b. ca 1846
5. Jacob Phillips b. 1863 m. Hannah Brown b. 1867
….and so on….

mtDNA Lineages follow a mother’s mother’s mother and so on, an mtDNA should look like this:

1. Rachael Smith b. 1788 GA m. John White b. 1782 GA
2. Margaret White b. 1806 SC m. Nathanial Green b. 1801 SC
3. Mary Green b. 1831 TX m. Thomas Brown b. 1827 TX
4. Sarah Brown b. 1859 TX m. Mark Jones b. 1851 OK
5. Tempy Jones b. 1890 OK m. William Conner b. 1888 OK
….and so on…

In an mtDNA Lineage, you can see the surname of the female changes from generation to generation. In the Y-DNA Lineage, the surname remains the same unless an NPE (non-paternal event) takes place. When researching a Y-DNA line, it is common to focus on the surname as it is usually constant. For example, when researching John Phillips b. 1756 in VA, one assumes they are looking for a father with the Phillips surname.

To produce a useful mtDNA Lineage, it is necessary to avoid the temptation to use a husband’s surname as a substitute for the wife’s birth name when posting the EKA of a maternal line. Because the surname of a maternal ancestor changed from generation to generation, it is necessary to be more attentive to the maternal line’s details.

Suppose it is known that Rachael Smith’s mother’s name was Elizabeth, but Elizabeth’s birth surname is unknown. Perhaps you know that Elizabeth married a John Smith and had a daughter Rachael Smith. You might even know that Elizabeth was b. in 1759 or any other possible piece of information. Unless Elizabeth was a cousin of John Smith or by chance was Smith, her birth surname probably would not have been Smith. You could report this as Elizabeth mnu (maiden name unknown) b. 1759 m. John Smith.  Keep in mind that when someone is researching it is better to have a surname for reference.

What is a Haplotype?

The term “haplotype” is a contraction of the term “haploid genotype”.  In genetics, a haplotype is a combination of markers (technically called alleles) at multiple locations on a single chromosome.  Many genetic testing companies use the term “haplotype” to refer to an individual collection of short tandem repeat allele mutations (STRs) within a genetic segment, while using the term “haplogroup” to refer to the single nucleotide polymorphism mutations (SNPs) which determine the clade to which a collection of haplotypes belong.  To put this into layman terms, a haplotype is an individual’s set of values for the markers that he has had tested.  If two individuals match exactly on all of the markers they have had tested, they are said to share the same haplotype and to be related.  The degree of relatedness can be predicted based on the number of markers that have been tested.  The more markers tested and compared, the better and more accurate the prediction.

Mitochondrial DNA Explained

Mitochondrial DNA is also referred to as mtDNA. There are a total of 37 genes in mitochondrial DNA. The majority of them provide instructions for making transfer RNAs (or tRNAs) and also for making ribosomal RNAs (or rRNAs). Both of those types of RNA can take amino acids and assemble them into functioning proteins.

Mitochondrial DNA (mtDNA) is genetic material found in mitochondria.  It is passed down from mothers to both sons and daughters, but sons cannot pass along their mothers’ mtDNA to their children.  This is because mtDNA is transmitted through the female egg.  The mtDNA found in the egg is nonrecombinant, meaning that it does not combine with any other DNA so that it is passed down virtually unchanged through the direct maternal line over the generations.  You inherited your mtDNA exclusively from your mother.

The mtDNA test is more of an anthropological test than a genealogical test.  From a genealogical standpoint, mtDNA is not very useful for two reasons.  The first reason is mtDNA cannot be tied to any specific surname.  Why?  Because you inherited your mtDNA from your mother, who inherited it from her mother, who inherited it from her mother, and so on back in time.  Traditionally, women in Western cultures change their surnames when they get married, so your mother did not have the same surname as her mother, who did not have the same surname as her mother, etc, etc.

The second reason mtDNA is not very useful for historical genealogical research is because mtDNA mutates very, very slowly – much slower than yDNA.  This means that your mtDNA is nearly identical to the mtDNA of your straight line maternal ancestor who lived thousands of years ago, and it is also identical to thousands of people living today.  My mother has over 1,000 low resolution mtDNA matches in the FTDNA database.  This means she shares a common maternal ancestor with them somewhere back in time.  The problem is there is no way to know whether this common maternal ancestor lived recently or thousands of years ago.

In terms of recent kinship, mtDNA works best at disproving relationships rather than proving them.  For example, if your mtDNA is not the same as your mother’s mtDNA, this means she is not your biological mother and you were adopted.  However, it is much more difficult (if not impossible) to tell from your mtDNA alone exactly who your biological mother really is, because your mtDNA is going to match the mtDNA of thousands of women.

WHY MITOCHONDRIAL DNA IS IMPORTANT TO GENEALOGISTS

Genealogists seek out information about their relatives and ancestors. They want to know how everyone is related to each other and to “fill in the blanks” where information is missing. Mitochondrial DNA can help genealogists discover new relatives, find out more about their heritage, and provide matrilineal information.

Mitochondria is part of a cell. Its main function is to convert energy from food into a form that the cell can use. The process is called oxidative phosphorylation. Mitochondria also can help regulate apoptosis (which is the self-destruction of cells) and are necessary for the production of cholesterol and part of hemoglobin.

Mitochondrial DNA is also referred to as mtDNA. There are a total of 37 genes in mitochondrial DNA. The majority of them provide instructions for making transfer RNAs (or tRNAs) and also for making ribosomal RNAs (or rRNAs). Both of those types of RNA can take amino acids and assemble them into functioning proteins.

Genealogists who want to learn more about their mitochondrial DNA can make use of a mtDNA test. This type of test can trace a person’s matrilineal ancestry. Every person gets his or her mtDNA from their mothers. Fathers cannot pass mtDNA to their children.

This means that information about a person’s mtDNA can help a genealogist to locate other people who match their matrilineal ancestry. The mtDNA is passed from a mother to her children unchanged. A perfect match between one person’s mtDNA and that of another indicates that the two people have a common ancestor (and that the ancestor is female).

Genealogists can run into “roadblocks” when they try to research their female ancestors. If the ancestor got married, she more than likely changed her surname. What was that ancestor’s “maiden name”? That information can be found on her birth certificate. If her original surname cannot be found, it could cause an entire branch of a family tree to be lost to history.

Genetic testing that involves mtDNA is an opportunity for genealogists to connect to those missing branches. The test results can identify the genealogist’s mtDNA and use it to identify the genealogist’s female ancestors. It can only go so far, though, because it is possible for mtDNA to mutations to occur. Each mutation connects with a specific haplogroup.

The other important thing to know about mtDNA testing is that both female and male genealogists can have that type of test performed. Only women can pass their mtDNA onto their children. However, all her children will receive it, whether they are male or female. Men cannot pass their mtDNA to their offspring, but they can still have their own mtDNA tested.

Image by John Atherton