Were the Neanderthals Human?

(a continuation of "Who was Mitochondrial Eve")

 

All Europeans have some small measure of Neanderthal DNA within the mix received from both parents.  Even so, no one alive today has been found to have a Neanderthal mitochondrial DNA signature or Y-chromosome DNA signature.  However, the mixed autosomal DNA within each of us proves that at some point in our ancestral past, people with European descent connect to Neanderthals. Many scientists classify Neanderthals as Homo sapiens neanderthalensis, a subset of the human branch, rather than a parallel branch. If we include the Neanderthals, our common maternal ancestor is further back in our ancestry than Mitochondrial Eve.  Neanderthals lived in Europe for about 350,000 years—and in the Middle East even longer.  Neanderthals’ ancestors lived in Africa 600,000 years ago—nearly three times older than the “Mitochondrial Eve” of the currently living human population.



This Neanderthal reconstruction is from the
Neanderthal Museum in Mettmann, Germany

My 23andMe DNA test and National Geographic DNA test both confirm that 3.2% of my uniquely human DNA markers are specifically Neanderthal.  That’s a small percent, but it says something special about my ancestry 25,000 years ago. Archeological evidence reveals Neanderthals to have lived in southern Europe up to about 25,000 years ago.  Their extinction was not exactly a genetic extinction, but rather, an assimilation.  My anatomically modern human ancestors moved from Africa through the Middle East and began to arrive in Europe about 43,000 years ago.  For nearly 20,000 years there existed an admixture of these populations—Neanderthals who resided in Europe, and the more sender, agile, anatomically modern humans, who arrived in Europe from the Levant.  Modern humans overtook the Neanderthals, yet they remained strong enough to leave their mark on 3.2% of my DNA.

Approximately a thousand human generations elapsed within the last 25,000 years.  That’s a lot of ancestors to document.  Of course many of our ancestral lineages converge together much more recently than 25,000 years ago.  My DNA suggests that 3.2% of those ancestors were Neanderthal, having distinctive mitochondrial DNA as found in my DNA comparison report. While Neanderthal autosomal DNA survives in the present human population, Neanderthal mitochondrial DNA at some point became extinct.  We don’t know when that extinction occurred, except to say that it is certainly more recent than our most recent archaeological samples of Neanderthal—more recent than 25,000 years ago.

If we bundle these Neanderthal ancestors into the category of what it means to be human, we push the convergence point of all humans back much further in time. The African ancestors of Neanderthals and anatomically modern humans converged between 600,000 and 800,000 years ago.  Personally, I classify Neanderthals as human.  They are certainly closer to anatomically modern humans than any other primate alive today, even with their own distinctive features included.

Anthropologists who study human evolution categorize these earlier ancestors as “archaic humans.”  If we look back 600,000 or more years, there are clear physiological differences between us and our ancestors in the archeological record.  There are also clear intellectual differences.  Should we consider these ancestors human?   It depends on our definition of human.  We have archaeological evidence that archaic humans utilized fire as early as a million years ago.  Our means of successfully controlling fire (at least some of the time) sets us apart from the rest of nature.  This mastery of fire included a complex level of imagination, discernment of risk, and very likely was combined with a sense of spirituality—all distinctive characteristics of humans. 

I’ll defend that the definition of human should be pushed back even further than our mastery of fire.  At some point in our ancestry there was a first person to imagine where the sun went after it set on the horizon at night.  This person, of course, had no idea where the sun escaped only to return on the opposite horizon the next morning. But somehow this early ancestor was able to imagine the question, and convey that message to others.  After the first human raises the question, of course there were others who pretended to know the answer.  This is a new level of socialization, again, as far as we know, distinct among humans.

The sun always returned on the other end of the sky the next morning.  These repeating cycles, built into nature itself, gave our ancestors the necessary level of order combined with mystery to begin a voyage of discovery.  That voyage led to the mastery of fire and to deeper questions.  Fire is here with us, but also in the sky. We need fire for warmth and light, yet fire can also destroy us.  Water destroys fire. We need water for life, yet water can also destroy us.  All the basic questions of life emerge out of our relationship with nature.

At what time in prehistory do we begin to ask questions of our experiences?

For countless generations, our ancestors went into the river to bathe, to cool down, to play, to drink.  For countless generations, our ancestors felt the flow of that water.  Yet at some point there was a first person who began to raise new questions.  Looking upstream, she pondered, “Where does this water begin?”  Looking downstream, she pondered, “Where does this water lead?”  These are human questions.  These questions are our own way to engage the mystery that surrounds us, the mystery that is in us. 

I think it’s these questions, ones that occurred very early in our ancestry, that make us human.

 

Who is "Mitochondrial Eve?"

In the Biblical account, after the first humans were banished from Eden, Adam named his wife “Eve,” a name symbolizing she would become “mother of all the living” (Gen. 3:20).  Our mitochondrial DNA also reveals that we descend from a common female ancestor, and hence we colloquially call this ancestor “Mitochondrial Eve.”  Who are we talking about when we use the term “Mitochondrial Eve?” 

A 1988 article by Newsweek is among the
first popular articles to discuss
Mitochondrial Eve. 

Mitochondrial Eve is defined by geneticists as the most recent matrilineal ancestor of all humans alive today.  Since mitochondrial DNA is inherited directly from one’s mother, uncombined with any DNA of a male ancestor, it can only change due to mutations.  Those mutations are traceable, through maternal ancestry.  The mutations are nested, in that a certain mutation, let’s name it “B” always occurs when “A” is also present.  However, the opposite is not true: “A” can be present without “B.” Therefore one can determine which mutations occurred more recently and which ones are more ancient.   In this example “A” is older than “B.”  This nesting pattern is the scientific basis behind the study of cladistics.

As we trace mtDNA haplotypes back through time we encounter less and less human genetic variation, and ultimately converge to a single, common matriarchal ancestor.  My haplotype T2b2, descends in an unbroken chain from T2b > T2 > T > JT > R2’JT > R > N > L3, and then  through several steps in haplogroup L back to Mitochondrial Eve.  Every person’s tree will lead back to Mitochondrial Eve. Although we cannot pinpoint an exact generation or date in which the maternal convergence of all humans occurred, it was sometime around 10,000 generations ago, approximately 200,000 years ago.  However, don’t get caught up on this convergence as a specific “event” in its own time. This convergence only has meaning from the perspective of our modern time (in this generation). Here’s why:

Think of it this way.  The set of humans presently alive is approximately 7.3 billion. This large number is only a subset of the number of humans who have ever existed.  If, say 500 years ago, we were able to take DNA samples from across the ethnic groups of humans alive, we would find lineages that have since become extinct, particularly among indigenous peoples whose lineages have been exterminated by the impact of colonialism.  Some of those extinct lineages, particularly in Africa, would descend from the basal branches of our current tree. Therefore the “Mitochondrial Eve” of 500 years ago was an earlier ancestor of the “Mitochondrial Eve” we have today.  The trunk of the tree would need to be extended back further to take into account the lineages that went extinct.  The female ancestor that unites all people living 500 years ago would have herself lived earlier than Mitochondrial Eve, as defined today.

We should also note that basal lineages are no closer to our ancestors than ourselves.  We are all the same distance, both in generations and time, from our early ancestors, whether we are African, Asian, European or Native American.  There is more human genetic diversity in Africa, so it is clear that continent is our origin, however it is a misrepresentation to believe that basal branches have a closer connection to our ancestors.

Typical male response to the bigger questions of life?

In no case is Mitochondrial Eve the sole human female in existence. On the East African prairie 200,000 years ago, there were many interrelated tribes of humans.  Eve is simply the one female from whom we all descend via an unbroken maternal lineage.  Everyone descends from mitochondrial Eve the same way, through their mother.  While many of her contemporary friends and enemies were also our ancestors, we descend from the others in a complexity of paths via fathers and mothers.

Scientifically, the maternal ancestor of all humans alive today is not the first female human that ever existed, so the name “Mitochondrial Eve” is a bit of a misnomer.  The “first human” is not easy to define because DNA mutations proceed back through time eventually to converge with a similar progression arising from the chimpanzee branch of the tree of life. At what time and at what place along this branch can we define the first human?  That depends on our definition of human. But first, where do the Neanderthals fit in?  That's the subject of the next blog.

At locus #930 I have the chimp marker instead of the human one!

     Yes, as strange at it sounds, I encountered something a bit crazy in my own mitochondrial DNA at location #930.  I've been comparing my genome with other humans to determine variation, but also with chimps and bonobos found in the databases at NCBI, and the Neanderthal and Denisovan samples extracted under the direction of Svante Paabo at the Max Planck Institute for Evolutionary Biology in Leipzig, Germany.  Step by step, base by base, I'm comparing the data, and found 30 distinctive markers separating chimps and humans among the first 1,008 base pairs analyzed.


Jane Goodall spent her life exploring the psychology and sociology of chimpanzees

    But at marker #930 something strange occurs.  Humans have a G (guanine) in this position.  Chimps and bonobos have an A (adenine).  However, my own DNA has an A!  I have the chimp marker, while humans (or to be clear, most humans) have a distinctive human marker.  How could this be? 
    It so happens that my mitochondrial DNA signature belongs within a specific haplotype known as T2b.  The mutations in my DNA can be arranged chronology and traced back to a founding population in Africa, ultimately connecting to every human on Earth--if you trace back far enough. The same is true for your own haplotype. My haplotype T2b descends from T2, which descends from T, which descends from JT, which descends from R, which descends from N, which descends from L3 all the way back to Africa. 
    So how did I end up with a supposedly distinctive chimp marker?  Well, apparently my value 930A was not original to my ancestry.  Haplotype T2b is defined by a mutation G930A (meaning the "G" mutated to an "A" in position 930).  It so happens that the "A" is the chimp value, seemingly by coincidence.  This doesn't mean I have more chimp ancestry than you.  It only means that I have a specific marker that mutated back to the value found in chimps today.  Back before chimps and humans existed we shared common ancestor.  I'm uncertain if that ancestor had a "G" or an "A" at position 930.  Therefore, I place G/A in red in that position on my report found here.  As I expand my study to include other diverse primates, I may be able to determine an original value.  After all, there are only two choices.  I have never found a "C" or "T" in this position. Perhaps the mutation occurred in the chimps from an original "G."  Perhaps the mutation occurred in humans from an original "A."  Perhaps this marker switches back and forth in both populations in prehistory.
    I don't have many chimp samples to work with, but so far all chimps I've studied have an "A" at position 930.  On the human side I have 20,600 samples, and I found this "back mutation" to the chimp value in seven lineages, in haplotypes L1c6, L5a1, L2a1c1, M1a1b, M44a, D4h3a1a, and T2b. It includes less than 3% of the world's human population.  Haplotype T2b is the most populous of these seven lineages that share G930A.  It is concentrated in central Europe.
    I think I can confidently state that marker 930 has shifted from the "G" to the "A" throughout human history--at least in seven instances.  Compared to most mitochondrial DNA markers, this position mutates rapidly.  Part of the outcome of my study is to determine which markers mutate rapidly and which markers are especially stable.  In comparative genetics, a difference in a fast mutating marker is not as significant as a difference in a slow mutating marker.  I have access to 20,600 human genomes, upon which to determine which markers mutate more often than others.  That's quite a lot of data.  More data allows for better conclusions.  What was thought of as a distinctive chimp marker is actually part of the DNA that overlaps between humans and chimps.  There are other markers like this as well.  I notate them all, base by base,  in my report.


   

Comparing DNA - What's the Process?

     Actually, for those that don't know the process, it's quite simple.  DNA sequences for many species are publically available through the National Institute of Health (NIH), by way of their affiliate, the National Center for Biotechnology Information (NCBI).  The NCBI maintains an ever-growing genomic database representing the vast diversity of life forms on earth. You can simply select a species and then download its genome.

     Any given genome is only an individual genetic representation of that species.  A collection of ten genomes of Pan troglodytes (the common chimpanzee), for example, will show some level of variation.  Therefore, mapping ten chimp genomes, and taking into account all the genetic variation of those ten individual chimps, provides a better comparison between species than simply having access to one sample. There is always some measure of genetic overlap between closely related species.
    This is the biological complexity of which we are a part.  Life is on a genetic continuum.  And genetics largely expresses itself in physiology.  The reason chimps are physiologically very similar to humans is based in the reality that our DNA sequences are very closely matched to theirs.
     Accurate methods which compare the similarity of chimp and human DNA will account for the variation within each species.  Fortunately, through www.phylotree.org, we have a publically available database of 20,600 human mtDNA genomes upon which to drawn information concerning this variation on the human side of our puzzle.  We have no such luck of the chimp side.  There are only an estimated 170,000  to 300,000 chimps left in the wild, reduced from a population of over 2 million that existed in 1995.
    My study includes three diverse samples, one common chimp (Pan troglodytes) from Gabon, one western chimp (Pan troglodytes verus) from Senegal, and a bonobo (Pan Paniscus) from Congo.  The bonobo, also known as the pygmy chimpanzee, was first sequenced in 2012.  My study lacks variation on the chimp side.  My results show 97.02% similarity across 1,008 base pairs.  We are at least that similar.  If I had more chimp samples to work with, the potential overlap could be slightly higher.
    Genomes are stored in a format known as FASTA, basically the list of the nucleotides A, G, C, T, in the order that they appear in the DNA sequence.  Mitochondrial DNA is a circular molecule, on average about 16,569 nucleotides long in a human, and (on average) about a dozen less in a chimpanzee.  The FASTA data can be downloaded into a spreadsheet and then compared base by base.  Being circular, mtDNA has no naturally defined beginning position or end position.  The NCBI data begins with the first mtDNA gene, what geneticists define as the "coding region." For family history DNA researchers, this is position 577. The NCBI data then wraps around so that the last nucleotide is position 576.  I follow the numbering system established by Bryan Sykes at Oxford in the 1990s. If you have your mitochondrial DNA mapped through a testing service such as FamilyTreeDNA, the results will follow the same numbering system as my report.
    I first align the sequences so they are starting from the same position, and then I compare each base to base.  When I encounter a distinction between any of the samples in the study, I flag it in yellow and provide a notation.  In my current study, found here, The first 28 positions are exactly the same. A distinction is found at position 29, as two of the chimp genomes exhibit G (guanine), while all the human samples (including myself and two other anonymous individuals) exhibit C (cytosine).  In addition the Neanderthal and Denisovan samples in the study exhibit C at position 29.  At first glance this looks like a marker distinct between chimps and humans.  However, when the bonobo sample is assessed, we find the bonobo shares a C at position 29, the same as the human samples and opposed to the G shared between the western chimps and common (Eastern) chimps.  Therefore position 29 is not a marker distinct between chimp and human populations. 
    Based on this marker alone we would conclude the bonobo subspecies of chimps are more closely related to humans than western or common chimps.  As we move down the sequence, will find this confirmed, in part.  As we move to position 40, we find the chimp samples again don't match the human ones.  The bonobos have a G where the human have a T, and the western and common chimps have a C.  Here our first distinct marker between chimps and humans.  The T to C mutation (or vice versa) is called a transition, and is about three times more likely to occur than a transversion (T to G), simply based on the chemistry of the molecules as they replicate. 
    I continue this comparison through the first 1,008 bases and find 30 markers distinct in chimp populations compared to human populations...I'll point out more of these distinction in the next few days...

A base by base comparison of chimp and human DNA

     It's been a sideline interest of mine to determine, genetically, how similar we really are to our closest cousins on the tree of life.  Since 2008 I've been using DNA to trace family history, revealing ethnic ancestry and the close relationships between seemingly unrelated surnames.  DNA analysis has traced our lineages back further, and yielded all kinds of diverse information unknown through paper records alone. 

     Of course the same methodology can be used to trace back further, beyond (and before) the time of anatomically modern humans.  We now have a several complete Neanderthal genomes, and DNA from the recently discovered Denisovan fossils in southern Siberia.  Genetic anthropologists also have the reconstructed genome of "Mitochondrial Eve," the maternal ancestor to all living humans.  We know this DNA sequence not because we have identified a fossil of such an ancestor, but rather we have traced back the nested mutations of all humans tested to date, and have reconstructed what this "original" genome looked like--at least in reference to mitochondrial DNA.
    Genetic anthropologists define "Mitochondrial Eve" as the most recent human ancestor of all living human populations today, and therefore automatically exclude Neanderthal, Denisovan, and all other archaic human populations that are now extinct.  Now we have genomes from these ancient ancestors.  Doesn't it make sense to determine genetically how they (and us) fit into a primate tree?  There are plenty of samples of chimp and bonobo DNA available as well. All the DNA required to construct a base by base comparison is available to the public.  Someone just needs to begin the painstaking work of documenting the comparison piece by piece, aligning the sequences, discovering the insertions and deletions, recording every deviation and accounting for every variation within the populations tested.
     This work is far to important to be overlooked. If the differences between chimps and humans are based in genetics, then these sequence differences between our species are especially significant. Once compiled, we'll better determine what exactly defines us as human genetically.  As we learn what every difference means, there will certainly be surprises, I suspect surprises both in regards to our similarities and our differences.
    Human mitochondrial DNA is composed of 16,569 base pairs, a manageable number, easily contained within a standard excel spreadsheet.  So far, I've compared the first 1,008 base pairs, and found 30 absolute base-pair distinctions between "us" and "them."  That's 97.02% similarity.  The 3% tagged as distinct, must cause all the difference.
    Actually 25 of those absolute base-pair distinctions were found within the first 576 bases, what geneticists called the Hyper-Variable Region (HVR).  The other five distinct bases were found in the region 577-1008, a coding region where DNA expresses proteins, and is therefore less susceptible to mutations.  Most of the DNA moving forward in the sequence (beyond marker 1008), is also coding. I suspect the current 97% similarity will increase, perhaps to 98% or 98.5%, as I complete the comparison of the full mitochondrial genome of 16,569 bases. 
    A chimp/human comparison of the Y-chromosome should also reveal some interesting results, however our Y-DNA is something on the order of 59 million base pairs long, so for now I'll focus on the mitochondria.   You can download a pdf of my work in progress, a base of base comparison (57 pages) of the first 1,008 nucleotides here.