Complicating the Family Tree

Our view of our past keeps getting more complicated. Our family tree, it turns out, is more of a twisted vine than a neatly linear branch.

Evidence keeps building by the day that our anatomically modern human (AMH) ancestors interbred with earlier forms of “archaic” humans. In the 31 Oct 2011 early online issue of PNAS, Pontus Skoglund and Mattias Jakobsson present evidence for the view that the genetic legacy of the Denisovans is wider than ever thought before.

First is was the Neandertals. This branch of the human family diverged from our own somewhere around 500,000 years ago. Somewhere between 100,000 and just 50,000 years ago, however, AMHs and Neandertals interbred successfully. The result lives on today in our genes. For many of us, our DNA is 2-3% from our Neanderthal ancestors. The Neandertals may be extinct, but their DNA lives on in every cell in the human body.

Then it was the Denisovans, a recently discovered branch of the human family more closely related to Neandertals than to us. What about AMH-Denisovan iInterbreeding? An international team of researchers led by Svante Pääbo of the Max Planck Institute for Evolutionary Anthropology in Leipzig was able to extract Denisovan DNA from tiny fragments of remains. From the extracts, they reconstructed the Denisovan genome and compared it with the human genome. What they found was clear evidence of interbreeding. Some living human beings—those identified as Melanesians—carry Denisovan genes. That was reported in December 2010.

In September, however, Pääbo was joined by David Reich and Mark Stoneking and other colleagues in reporting that the legacy of Denisovan DNA extends beyond the Melanesians. It’s all over the islands that extend below Southeast Asia, including Australia. Not just Aboriginal Australians but Near Oceanians, Polynesians, Fijians, east Indonesians, and other groups as far as the Philippines are carriers of the Denisovan legacy.

According to this study, the genetic legacy of AMH-Denisovan admixture does not include East Asians. This led the authors to conjecture that there are at least two main waves of AMH migration into southeast Asia. The first wave interbred with Denisovans while the second, apparently, did not.

Their work appeared in the 7 Oct 2011 issue of the American Journal of Human Genetics. Reich discusses these findings in a video. Hint: start at minute 22:30.

But now a study published in the online early edition of the Proceedings of the National Academy of Sciences for the week of 31 Oct 2011 presents evidence that East Asians are also descended in part from the Denisovans. In the paper, the authors (Pontus Skoglund and Mattias Jakobsson) write that “we found a significant affinity between East Asians, particularly Southeast Asians, and the Denisova genome.”

Experts in the field will no doubt debate these findings. Just how widespread is the effect of AMH-Denisovan interbreeding? How widely did AMHs and archaic humans interbreed? To what extent does admixture provide any benefit? Does it shed any light on observable differences between different groups within the human family today?

According to Skoglund and Jakobsson, the “history of anatomically modern and archaic humans might be more complex than previously proposed.”

If our past is more complex than we thought, so is our present. What does it mean to be human? It no longer seems to mean that we are all part of a biological species. Whether we like to call ourselves "anatomically modern humans" (AMHs) or Homo sapiens, we are learning that the very concept of species is becoming unfocused by research. Should we speak of AMH-Denisovan "interbreeding" or "hybridization"? Does it matter? Are we separate species or one slightly-tangled humanity?

Science and Human Mystery

I have been reading Bernard McGinn, a foremost expert on the history of Christian spirituality and mystical theology. In a recent essay, he comments on “the importance of recognizing the mystery of human existence.”

In Christian theology, the mystery of the human is grounded in the mystery of God. In the fourth century, St. Gregory of Nyssa observed that human beings are in the image of God. Our nature mirrors God’s nature. If God is inexhaustible mystery, then what we are must always remain a mystery to ourselves. Otherwise, our knowledge of ourselves would serve as something of a key for us to figure God out, a kind of theological Rosetta stone.

What does this have to do with recent science? Some think that science finds facts and dissolves mysteries. McGinn suggests as much. He thinks that theology’s insistence on human mystery serves as a useful check on the de-mystifying pretensions of science.

I agree with McGinn about the theology of essential human mystery. But I disagree that science has a tendency to erase mystery. Sure, many people see science that way. But look again. The more we learn about human origins, the more we find that any clear notion of a distinct human species seems to unravel. The more scientists merge human and nonhuman organisms or blur the distinction between human and machine, the more we make ourselves mysterious.

If I am right, science increases mystery. At least that’s what I tried to suggest in the brief article I contributed to Science last February. For more, see my post for October 12, below.

That’s why I think McGinn is not quite right when he say this:

“If God is the ultimate mystery, man’s image-nature implies an essentially negative horizon, or limit, to all that can be scientifically discovered about humanity, however original, illuminating, and productive these findings may be. From this viewpoint, growing scientific information (i.e. more and more facts) about human nature (biological, psychological, and sociological) will always be limited by the realization that the true meaning of human existence rests in its status as an inexhaustible mystery. Scientific contributions to the deeper understanding of human nature are welcome and often useful in the task of human self-realization, but they take on a different color when viewed from the sapiential perspective of the “learned ignorance” (docta ignorantia) that recognizes the limits of what can be known and quantified about humanity. This recognition of the limits of science may not be an easy message for contemporaries to appreciate, enamored as we are by the amazing discoveries about homo sapiens made during the past century; but it is one of the most significant challenges that image dei anthropology offers to the present.”

McGinn’s essay is entitled “Humans as Imago Dei: Mystical Anthropology Then and Now.” It appears in Sources of Transformation: Revitalising Christian Spirituality, 2010.

A New Approach to Enhancement?

Some people object to human germline modification because they do not like the idea of one generation messing with the DNA of future generations. Even worse, they say, is modifying the genes for the sake of…gasp!...enhancement!

But now comes a tantalizing study in tomorrow’s issue of Nature hinting at the possibility that what we do to live longer may change the lifespan of our grandchildren. It’s only a hint—the research reported here involves the faithful nematode, Caenorhabditis elegans. By exposing one generation of these tiny worms to just three proteins, researchers in Anne Brunet’s lab at Stanford produced worms that live up to 30% longer. The surprising thing is that the enhanced lifespan was passed to the next 2-3 generations. The really surprising thing is that the lifespan of the C. elegans great-grandchildren was enhanced even though no DNA sequences were modified. In other words: germline enhancement without genetic modification.

How is that possible? Epigenetics. The three proteins changed the way the DNA is structured or packed without changing the DNA code itself. Such epigenetic changes can change the way genes are expressed. The effect can be dramatic—in this case, a 30% longer lifespan. What’s more, the epigenetic change can be passed to future generations. Most often, epigenetic changes are reset during reproduction. But in some cases, epigenetic modifications are passed to the next 2-3 generations. When that happens, the structure and the expression of DNA are changed even though the DNA sequence remains unchanged. Over time, however, the effect washes out so that the great-great-grandchildren are back to the starting point.

Will this epigenetics-to-lifespan relationship be found in human beings? Who knows. Again, it must be repeated: this research involves flatworms. Humans are just a bit more complicated. Already, however, Brunet’s lab is looking for something similar in mice and in African killfish.

Whether anything similar will be found in human beings, this research already suggests a truly interesting thought experiment. Suppose this leads someday to a human-application technology. Would it be opposed by those who object to human germline modification? Sure, future human beings would be changed without their consent. But no genes are changed, and the changes are not permanent.

Perhaps the more sobering thought is this. Maybe this research will lead to a startling discovery. Never mind some new technology. Might it turn out that what health-minded human beings normally do—eat their green vegetables, get their exercise—has the effect of enhancing their offspring by modifying the expression of their genes by means of generating inheritable epigenetic changes? Could be. If just three proteins make C. elegans progeny live 30% longer, just imagine how your dinner might change your grandchildren (assuming, of course, that you’re in your reproductive years or younger).

The article, “Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans,” appears in the October 20 issue of Nature.

Evolution and the Human Brain

How did the human brain become so complex so quickly? Did old genes learn new tricks? Or did new genes appear, bringing new functions?

A paper appearing today in PLoS Biology suggests that new genes play a bigger role than previously thought in explaining the complex functions of the human brain. Researchers at the University of Chicago Department of Ecology and Evolution reached this conclusion by comparing the age of genes with transcription data from humans and mice. Where are new genes most often expressed? In humans, it’s in the brain. Even more interestingly, it’s in the developing brain of the fetus and the infant.

One of the researchers, Yong E. Zhang, was motivated to ask these questions because he accompanied his pregnant wife to prenatal ultrasound appointment, according to a press release issued by the University of Chicago Medical Center. According to Zhang, “Newer genes are found in newer parts of the human brain.” The press release also quotes co-author Patrick Long: “What’s really surprising is that the evolutionary newest genes on the block act early….The primate-specific genes act before birth, even when a human embryo doesn’t look very different from a mouse embryo. But the actual differences are laid out early,” Long explained.

In the language of the PLoS Biology paper, the authors “observed an unexpected accelerated origination of new genes which are upregulated in the early developmental stages (fetal and infant) of human brains relative to mouse.” In other words, compared to all the genes in the human genome, younger genes are significantly more involved in those parts of the brain that make us distinctly human. More than that, these genes play a greater than expected role in prenatal and infant development, the very period in which the brains of humans develop so rapidly compared to the brains of other species.

How did these new genes arise? By all the various means by which new genes arise—by various processes of duplication and by de novo origination. Rather remarkably, the authors make this observation: “…young genes created by all major gene origination mechanisms tend to be upregulated in [the] fetal brain. Such generality suggests that a systematic force instead of a mutational bias associate with a specific origination mechanism contributed to the excess of young genes in the fetal brain.”

What “systematic force”? Clearly, the authors are not speculating about anything more than a statistical correlation. But their work will give rise to new questions for research. What role do these young genes actually play in the developing brain? What role did natural selection play in the evolution of these genes? Does this surprising correlation shed any light at all on our rapid rise as a species and the stunning complexity of the human brain?

The paper, "Accelerated Recruitment of New Brain Development Genes into the Human Genome," is published in the October 18 issue of PLoS Biology [10.1371/journal.pbio.1001179].

100,000 Years of Art

The awakening of human creativity is one of the great mysteries of our species. Even today we marvel at the artistic power of cave art, some of it dating back nearly 35,000 years ago. Musical instruments—flutes, at least—date back nearly as far. Beads, often made by carefully drilling a hole through shells, date to nearly 100,000 years ago.

And now comes evidence to suggest that painting goes back just as far. At least 100,000 years ago, about 40,000 years earlier than previously thought, human beings made pigments for paint through a process that is surprisingly complex.

In the October 14 edition of the journal Science, Christopher Henshilwood and his team present their analysis of the earliest known “artists’ workshop.” In the Blombos Cave in Cape Town, South Africa, they discovered a 100,000 year old ochre processing site. In two places in the cave, ochre was ground into fine powder, mixed with crushed quartz and other chemicals including charcoal and bone, and blended into a pigment mixture that was stored in two abalone shells. The pigment may have been used for painting, body decoration, or coloring of clothing.

"The recovery of these toolkits adds evidence for early technological and behavioural developments associated with humans and documents their deliberate planning, production and curation of pigmented compound and the use of containers. It also demonstrates that humans had an elementary knowledge of chemistry and the ability for long-term planning 100,000 years ago," concludes Henshilwood in a press release issued by the University of the Witwatersrand in Johannesburg. The article, "A 100,000-Year-Old Ochre-Processing Workshop at Blombos Cave, South Africa," appears in the October 14 issue of Science.

What is fascinating is how early all this occurred and just how complex the process was. It involved careful planning over time. It included surprisingly sophistical technology (one is tempted to say “chemical engineering”). Why? What was stirring then, and how are we still inventing new ways to release the human imagination?

Still wondering..."What Defines Us?"

Last February the editors of Science marked the 10th anniversary of the publication of the complete human genome. They invited a dozen or so people to contribute short reflections on the meaning of this milestone.

I was given 250 words for my article, entitled “What Defines Us?” In that small space I tried to suggest two things. First I noted a simple irony: As we gain more scientific information about our genome and our evolution, the philosophical and religious concepts of humanity become blurred or defocused. Second, I suggested that this defocusing need not be a cause for discomfort. Precisely because we are humans—whatever exactly that means anymore—we switch almost immediately from discomfort to wonder and excitement. The quick switch is what makes us human. I ended by asking: “Who are we, and where will we go next?”

It is as if we are making ourselves up as we go along. Recent discoveries in human evolution intimate just such a view. Anatomically modern humans are now believed to have interbred with Neandertals and with the more recently discovered Denisovans. Many of us carry the DNA of these extinct forms of humanity in our own genome. In that sense they are not distinct at all but live on in every cell of our bodies. More recently, it has been suggested that similar interbreeding occurred in sub-Saharan Africa.

Interestingly, it has also been suggested that interbreeding enhanced us. In August, a research article in Science suggested that our immune systems are more resilient than they might have been. Why? Because our ancestors interbred with Neandertals and Denisovans.

The evolutionary tree of humanity is beginning to look less like a tree and more like a tangled vine. And now we are led to wonder whether it is the tangle that enhances us. What makes us less clearly Homo sapiens seems, paradoxically, to make us more extraordinary as a species. Well…we’re running far ahead of the science here, but (as I suggested in Science), wondering is what makes us human. It’s not just the DNA; it’s what we dare to do with it.

I have been thinking about this recently because I will be speaking on November 10 on this very topic at the University of South Florida Saint Petersburg. They have planned an exciting lecture series, Festival of the Genome: Celebrating the 10th Anniversary of the Sequencing of the Human Genome, showcasing various perspectives on human genome research.