My Deep Ancestry

I can only recite a small bit of my ancestry. My father was born in 1909 in Hungary. His father died in 1914, forty years before I was born. His mother, who remarried, had additional children, his half-sibs. One of these, my uncle, was killed in World War II. I met my father’s mother a few times. She only spoke Hungarian and I only spoke English, so our contact was just some smiles, hugs, and laughs, no family stories.

My mother is Dutch, born in Holland. Her mother also came to the United States and lived in the city where I grew up, Youngstown, Ohio. My mother still lives in the house where I grew up, and at 89 is still going strong. She was an only child, but her mother had a brother, my great uncle, who I met on a visit to Holland in 1975. My great aunt and uncle were wonderful hosts, but we never got much into family history. As a child in a small nuclear family (father, mother, sister, brother, and grandmother), I never had much personal experience with extended families. I can’t rattle off my extended family tree, and the language of kinship – second cousins once removed, and so on – eludes me like the rules of some complex organized sport that I don’t follow.

I knew that my results from 23andMe were going to provide me with some insight into my deep ancestry. I knew that I was going to get two pieces of ancestry information right away: my mitochondrial haplotype and my Y chromosome haplotype. Each was going to give me a look at part of my ancestry going back thousands of years.

Mitochondria are subcellular organelles, found in the cells of all eukaryotic organisms (organisms with a nucleus). Plants, animals, protozoans, and fungi all have mitochondria. Mitochondria are the powerhouses of the cell, carrying out biochemical reactions that generate ATP, a chemical that provides energy for thousands of other reactions. Mitochondria have their own DNA, which encodes some of the proteins found in mitochondria. Mitochondria resemble bacteria in some ways, and are thought to be derived from endosymbionts – bacteria that a proto-eukaryote invited into its cells for mutual benefit billions of years ago.

Mitochondria and their DNA have the interesting property of being inherited exclusively from our mothers. Egg cells are much bigger than sperm cells and are packed with mitochondria. Sperm cells drop off a set of chromosomes during fertilization, but no mitochondria.

This means that my mitochondrial genome came from my mother, who got it from her mother, and so on back to my maternal great-great-great-grandmother and beyond. I have two parents, four grandparents, eight great-grandparents, and so on back through the generations to a very large number of ancestors. My nuclear genome has bits and pieces of my recent ancestors, but as you go back many generations, some of my ancestors are no longer directly represented there. Not so my mitochondrial DNA, which is an unbroken maternal line back through thousands of generations.

This would not be very informative about my ancestry, except that occasionally, mutations occur in mitochondrial DNA. Mutations in the coding sequences used to make mitochondrial proteins are usually very bad news and are eliminated through selection. There are some noncoding regions in the mitochondrial genome; mutations in these regions have no effect and are selectively neutral. Every time such a mutation occurs, it marks a new maternal lineage, branching off from the old lineage and continuing until another branch arises by mutation.

The rate at which these mutations occur is known, so we can say approximately when each new mitochondrial lineage arose. My results from 23andMe show my mitochondrial genome to be a type called H1. They show a map showing the frequency of mitochondrial lineage H1 in various populations around the world, shown below.

Clicking the history tab on this page at 23andMe tells me that haplogroup H1 originated about 13,000 years ago, not long after the end of the Ice Age. The people of Europe had been driven by ice sheets into southern France, Italy, and the Iberian Peninsula. The H1 haplotype likely arose in a woman living on the Iberian Peninsula. As the Ice Age ended, some of the descendants of this woman journeyed north all the way to Scandinavia, while others crossed into northern Africa. The blue on the map shows that H1 reaches a frequency of around 40% in Norway, far from its origins in Iberia, probably due to a founder effect. If a relatively small number of people founded the population of distant Norway, by chance the H1 haplotype is overrepresented there compared to Spain. My H1 haplotype is not a big surprise given my Dutch maternal ancestry, as H1 is common in Holland.

Men get extra information about their ancestry from 23andMe because of their Y chromosomes. The Y chromosome is one of the two sex chromosomes. Men are XY, women are XX. Normal human eggs have a single X chromosome as they await fertilization, while normal human sperm will either have an X chromosome or a Y chromosome. If the sperm fertilizing the egg carries an X chromosome, the zygote is XX and will be a girl, while if the sperm fertilizing the egg carries a Y chromosome, the zygote is XY and will be a boy.

This means that only men transmit the Y chromosome, and only to their sons. My Y chromosome traces back through my father, my father’s father, and so on back thousands of generations. Just like mitochondrial DNA, the DNA of the Y chromosome is subject to variation. Each time a new variant arises, it marks the beginning of a new paternal lineage. The rate at which these variants occur is known, so we can trace the origin of my Y chromosome haplotype to a specific time and place, just like for mitochondrial DNA. The 23andMe display for my Y chromosome is shown below.

My Y chromosome haplotype is E1b1b1a2*, a subgroup of E1b1b1a2 (also called E-V13) that arose in a population that moved from eastern Africa into northeastern Africa about 14,000 years ago, during the final days of the Ice Age. 23andMe reports that it is common among men in southern Europe, especially Greeks, Bulgarians, and Albanians. About 10% of Hungarian men carry this Y chromosome haplotype.

The Hungarian language is an odd one, related linguistically to Finnish, which reflects the migration of the Finno-Ugric people from the area near the Finnish-Russian border to what is currently Hungary in the 9th and 10th centuries. A search of the web for origins of the Hungarian people reveals a colorful history of repeated clashes with the neighboring kingdoms, especially during the 10th century. The reports of the geographic distribution of the E1b1b1a2 Y chromosome suggest that it did not come from the Finno-Ugric people. My Y chromosome likely came into Hungary from the outside.

In my search for the origins of the E1b1b1a2 Y chromosome, I found an authoritative account on Dienekes’ Anthropology Blog. Dienekes Pontikos presents the following conclusion:

The age and distribution of E-V13 chromosomes suggest that expansions of the Greek world in the Bronze and later ages were the major causes of its diffusion. Who was the E-V13 patriarch in Greece? He was perhaps one of the legendary figures of Greek mythology some of whom are said to have come from abroad. For whatever reason, his progeny grew, and were around to participate in the expansion of the Mycenaean world and the subsequent Greek colonization.

I have heard from a number of people who were forced to reevaluate their identities after getting results from 23andMe. My Y chromosome haplotype was the first result that made me question my view of my own identity. It is no longer as simple as being of “European” descent; now my paternal lineage traces from a movement of people in African to heroes of the Bronze Age in Greece, described much later in Homer’s epic poem The Iliad.

My mitochondrial and Y chromosome results pin down exactly two of my thousands of ancestors. What about all of the others? For this, we turn to my autosomal DNA, also analyzed by 23andMe. This is most of the 3 billion base pairs that make up my genome, and there is much to learn. Half is from my mother, and half from my father. Going back to my grandparents, about one quarter of my genome should be from each of them, on average, but here is where it gets messy.

The chromosome sets that end up in sperm or egg cells are the product of an elaborate cell division process called meiosis. During meiosis, homologous chromosomes replicate, pair, and then segregate from each other. The segregation process doesn’t work correctly unless the chromosomes are held together prior to segregation. Part of what holds chromosome pairs together is the process of meiotic recombination, in which chromosomes that are partly of maternal origin and partly of paternal origin are created. Because recombination takes place after chromosomes have replicated, chromosomes segregating into the sperm or egg might be entirely maternal, entirely paternal, or composite chromosomes made up of both maternal and paternal segments.

Each chromosome pair also segregates independently of all of the other pairs. This means that I only carry an average of 25% of each of my grandparent’s genomes. Tracing back through the generations, each of my great-grandparents is represented by an average of 12.5% of my genome, my great-great-grandparents by an average of 6.25% of my genome, and so on. The casino-like mechanism of sexual reproduction means that segments from some of my more remote ancestors are entirely absent from my genome, with the exception of my mitochondrial genome and my Y chromosome.

Can I learn anything about my ancestry by looking at my autosomal genome? It is best to start by asking what we might learn by surveying autosomal genetic variation across a large sample of people over the entire geographic range of our species. This has been done in increasing detail in recent years, and reveals a clear story of human history that supports independent evidence from anthropology and archaeology.

Imagine a population of individuals living in a particular area for many generations. There will be a certain level of genetic variation among these people. If a small group of people leaves this population to start a new population somewhere else, they will by chance leave some of their genetic variation behind. If a small group from the new population moves on, they will by chance leave some of their newly reduced genetic variation behind, further reducing their population’s genetic variation.

If the spread of people to new areas is rapid relative to the rate at which new genetic variation arises, which it is, we should be able to trace humanity to its original geographic location. This is easily done, and it is clear that human beings originated in Africa. Around 100,00 years ago, a small group of humans moved out of Africa to the Middle East, and spread from there throughout Europe, Asia, and eventually North and South America.

When humans first arrived in the Middle East and Europe, these adventurous people encountered an existing population of Neandertals. Neandertals are a distinct species that diverged from the human lineage about 600,000 years ago. Homo neandertalis is well known from the fossil record. In contrast to some of the stereotypes about “caveman,” we know that Neandertals used tools and weapons, cared for members of their population who were injured or disabled (often for decades), and buried their dead ceremonially with flowers and other objects.

It has long been of interest what happened when humans first encountered Neandertals. There are two broad hypotheses: displacement and admixture. Under the displacement hypothesis, humans outcompeted, drove off, or killed the Neandertals, driving them to extinction about 30,000 years ago. Under the admixture hypothesis, humans took a liking to their neighbors and interbred with them, preserving a bit of the Neandertal lineage among humans after Neandertals disappeared.

While it is easy to analyze fresh DNA that has been collected properly from people, analyzing DNA from fossils is not an easy task. While DNA is fairly stable, over thousands of years it breaks down into small fragments, and some of the bases undergo chemical changes. Nevertheless, some determined researchers have pushed this technique to the very limits. In 1997, Svante Pääbo and colleagues at the Max Planck Institute produced the first DNA sequences of Neandertal mitochondrial DNA (1). Mitochondrial DNA is easier than nuclear DNA because there are many copies of the mitochondrial genome per cell.

The answer was clear: there is no trace of the mitochondrial DNA of Neandertals among modern humans. It appeared that our species entirely displaced the Neandertals.

Techniques for sequencing DNA, including ancient DNA, have advanced rapidly. In 2010, Svante Pääbo and colleagues announced the results of sequencing genomic DNA from Neandertals (2). DNA recovered from the bones of three individuals was sequenced, producing data that reveals the sequence of most of the Neandertal genome. The sequence is, of course, very similar to the sequence of human DNA.

At each position of known SNP variation in humans, Svante Pääbo and colleagues asked whether the Neandertal sequence more closely resembles the sequence of human populations in Africa (where Neandertals never lived), Europe, or Asia. Upon making close to 100,000 such comparisons, Pääbo and colleagues made a stunning finding: the genome of Neandertals was more closely related to Europeans and Asians than it was to Africans. The average non-African appears to contain genomic sequences from Neandertals making up about 2.5% of their genome. Some people have more, some people have less. In contrast to the results of the work on Neandertal mitochondria, these results support the admixture hypothesis. The first people out of Africa encountered Neandertals in the Middle East and mated with them. Some segments of the Neandertal genome were advantageous, and have been maintained by positive selection 30,000 years after Neandertals became extinct.

I remember when these results first hit the science news. I talked to everyone that I could about it, including people not trained in science. It is a beautiful piece of work. For many scientists, there is nothing quite as much fun as finding out that something that is widely known by everyone is just plain, flat out wrong. Imagine that, people walking around today with caveman DNA. I took delight in it in an abstract kind of way.

After I got the email that my 23andMe results were ready, I moved to the ancestry portion of the site. Would I like to find out if I carried any Neandertal DNA? Sure, I thought, and clicked the link, revealing the display shown below.

I am 2.9% Neandertal, in the 92nd percentile among 23andMe users. When I first saw this, I stared at the screen for a while. I was a little bit shocked. I looked up a comparison of humans and Neandertals, showing two complete skeletons side by side. The Neandertal is described as “robust.” They were shorter, stockier, and barrel-chested. I started to identify with the wrong skeleton. I imagined how I look in a crowd of people. Shorter, stockier. Big shoulders. I ran my finger over my eyebrows and forehead to reassure myself. No brow ridges, high forehead. Human.

This was the first result from 23andMe that I discussed with other people. I found out that I’m mixed race, I’d say. They would usually pause, aware that for some this is a delicate subject. I’m 97.1% human race and 2.9% Neandertal, I’d say. Sometimes we would move on to the jokes to break the tension. I went for a long walk yesterday, I’d say. Boy, are my knuckles sore!

Some of my friends on Facebook consoled me. Your Neandertal ancestors were big-brained, gentle people, they reminded me. We know from the genomic sequence of Neandertals that they had a working copy of FOXP2, a gene required for language that is nonfunctional in our closest living relative, the chimpanzee. I began to look at many of the depictions of Neandertals in popular culture as insensitive. My Neandertal ancestors were not brutish, stupid ape-men, I thought. After a couple of weeks, I began to embrace my ancestry, boasting to others that I was probably more of a Neandertal than they were. One of my female colleagues who had heard of my ancestry told me that she tested as 3% Neandertal, and I felt disappointed, ordinary.

My colleague, Dr. Maggie Werner-Washburne, a consummate scientist, reacted well to the news.

“2.9%?” she said. She held up a hand to count on her fingers. “Let’s see: 50%, 25%, 12.5%, 6.25%,” then, touching her pinky, “3%. It hasn’t been that long for you, has it?”

The fast estimate that one of my great-great-great grandparents was a Neandertal would be a reasonable guess except that we know that Neandertals died out 30,000 years ago. This means that the parts of the Neandertal genome must have been under positive selection. Neandertals had been living in Europe for a long time when modern humans arrived, and were well adapted to the conditions there. Some of the Neandertal genome retained by the descendants of hybrids like myself are associated with the immune system, and were better for conditions in Europe than the African alleles my early human ancestors carried.

I recently registered for the Personal Genome Project, for which I volunteered to have my entire genome sequenced and made public. I was invited to the Genomes, Environments and Traits conference (GET2012) as part of the educational aspect of the project. I looked up the conference schedule and saw the keynote speaker: Svante Pääbo. I was hooked.

The GET 2012 conference was held on April 25. There were far too many wonderful things to write about in this post, so I will stick to Svante Pääbo’s talk. He held us spellbound with his unique combination of a low-key manner, wonderful data, and a few gentle jokes. He recounted the work on mitochondria, and how he made a public statement that we would never have the nuclear genome of Neandertals. Never make statements like that, he advised us.

He presented the arguments about displacement vs. admixture, showing that while the results from mitochondrial DNA favored total displacement, the results from the analysis of nuclear DNA clearly supported limited admixture. He presented the results from the analysis of a single bone fragment from a cave in Siberia that revealed another type of archaic human, now called a Denisovan, that is distinct from Neandertals and humans (3). Denisovan DNA makes up as much as 6% of the genome of some Melanesians. There is emerging genomic evidence that they may have been admixture in Africa with another type of archaic human for which there is no fossil record. The story is changing rapidly.

Pääbo closes with experiments with laboratory mice that have been genetically altered to make their FOXP2 gene match that of humans. It is a change of only three amino acids out of 714. The mice are run through a battery of tests to see if there is anything different about them. Amazingly, their vocalizations are altered. The audience is stunned. It is not exactly that they talk, but “medium spiny neurons have increased dendrite lengths and increased synaptic plasticity.”

Then, it’s time for questions. There are some good scientific questions until finally, someone asks the question that provides the perfect closer. The questioner points out that Neandertals were in western Europe for 100,000 years, but didn’t spread much. Humans moved out of Africa and relatively quickly spread everywhere: Europe, including the British Isles, Asia, and Australia. Why didn’t Neandertals spread?

Svante Pääbo reflected for a moment, then pointed out that most of the places where Neandertals never lived required them to do something that they didn’t like to do. They didn’t like to cross water if they couldn’t see land on the other side. He pointed out that many humans in boats must have died on the open ocean before the first humans reached Australia. So one of the differences between humans and Neandertals is that humans are crazy. They set out on ocean voyages without a clear idea of where they will end up.

I looked around at the auditorium, filled with participants in the Personal Genome Project who have made their genomes public, not knowing exactly what will happen. The rest of the crowd is a collection of forward-looking scientists, engineers, and venture capitalists. It occurs to me that I am looking at a group of people who all exhibit the most unique human characteristic: the willingness to set out on a voyage whose final destination cannot be clearly seen. Crazy. Human.