A Pinky’s Promise

In the summer of 2008, a multi-national team of Russian, European and American researchers found a small bone at a remote cave site in Siberia. At the time of discovery researchers had been working at the Denisova cave, located in the Altai Mountains in southern Siberia for several years already. Moreover, the cave was open to visitors as early as 2000, when it was listed on the program of The Second International Conference on Bioinformatics of Genome Regulation and Structure, held in Novosibirsk.

Initially, the discovery of a bone did not raise eyebrows, as the presence of Neanderthal people in the area between 48,000 and 30,000 years ago was a well-established fact. Interesting thus far, but nothing out of the ordinary.

As it turns out the small bone, identified as one of the bones in one’s pinky, held some surprises. Scientists at the Max Planck Institute in Leipzig extracted DNA – specifically mitochondrial DNA — and concluded that this type of DNA represented “a hitherto unknown type of hominin mtDNA that shares a common ancestor with anatomically modern human and Neanderthal mtDNAs about 1.0 million years ago.”  [For those scratching their head over the term “hominin,” this refers to extinct members of the human lineage.] So we are looking at one bone of a previously unknown hominin? Possibly. Or maybe not. 

The notion that we had several hominins living side by side, modern humans, Neanderthalers, and possibly this third species, should not come as a surprise. This happened quite frequently in our past; our existence today as the sole representatives of the human lineage is seen as an exception rather than the rule. What would be remarkable is that we have evidence of a human ancestor or close relative whom we did not know existed.

The latter realization has created a lot of buzz among those interested in human evolution. As is always the case with this type of endeavor, we need to be cautious and outline what we know, what the limits of our understanding are and where we shift from scientifically supportable reconstructions to pure speculation. A number of topics need further clarification here.

First, where does the owner of the bone fit in on the family tree, especially compared to us and to Neanderthals?

 Location of Denisova Cave and presumed place
on the family tree of the Denisova Cave specimen.

Researchers compared the Denisova mitochondrial DNA to complete mitochondrial sequences from 54 modern humans as well as a human who lived in Siberia about 30,000 years ago, six Neanderthals from more than 40,000 years ago, a modern pygmy chimpanzee and a modern common chimp. The results indicated that there are about 400 differences between us and the DNA in the pinky. This is twice as many differences as exist between modern human and Neanderthal DNA. This has led researchers to suggest that our last common ancestor lived about 1 million years ago, about twice as long ago as the common ancestor to us and Neanderthalers.

A second question that begs an answer is:  “what creature does this DNA belong to?” Various scenarios have been suggested here. It is possible, that we are dealing with a new species, neither modern human nor Neanderthal. Secondly, it could be a Neanderthal child, resulting from a union between a Neanderthal and an unknown species. Lastly it could be a Neanderthal individual, carrying variations in genetic make up thus far not identified in predominantly European samples.

The possibility that we are dealing with a completely new species is the most exciting. It is also one that most people caution us against. “Too soon,” “not enough material,” are some of the more common reactions. Others disagree and support the notion that this is a different species. This argument between those who see few species in the archaeological record (“lumpers”) and those who prefer a larger number of species (“splitters”) is one that has been described in a previous blog.

Skeleton of an alleged
Homo sapiens – Neanderthal
hybrid child found in Portugal.
Image courtesy of donsmaps

The scenario raising the possibility of an interspecies affair (between Neanderthal and another species) is favored by some, who see parallels with an alleged Neanderthal – modern human hybrid child found in Portugal. In this case, however, we would be looking at a child of a Neanderthal and a yet unknown species. This still implies that we had an unknown creature wandering the Siberian wilds, one whose genetics were inherited by a mixed offspring. In other words, this scenario still requires acceptance of the existence of an unknown species.

Finally it is conceivable that the breath of Neanderthal genetic variation is such that we have not mapped all of it. Given that most research on Neanderthals has concentrated on European materials, rather than Siberian, perhaps these Eastern Neanderthals carried in them a number of genetic variations that hark back to the original population in Africa. This would support the third option, one which identifies this pinky bone as belonging to a Neanderthal individual, albeit it with genetic markers not encountered in European samples. If identified as such, then this bone would reinforce the notion that Neanderthals occupied a much larger territory than originally assumed.

This discovery is meaningful in several ways. It illustrates that science marches on, providing answers to questions and, in the process, raises additional questions. It also shows how meticulous one has to work as an archaeologist or paleoanthropologist. One small pinky bone has provided us with a “what-in-the-world-is-this?” moment. The decision to perform a DNA test warns us not to be complacent. Up until recently, the party line about who was around some 40,000 years ago would have been answered with Homo sapiens or Neanderthalers, and nobody else. We are now forced to entertain the possibility of a hitherto unknown species living side by side with the other two. That is the promise this one tiny pinky bone holds.

A few final comments and thoughts.

What most articles I have read do not elaborate on is the fact that research is now happening in Siberia. This is a huge territory, difficult to access for all kinds of reasons. When discoveries like these are made, we should not be surprised that they generate questions we cannot answer yet, as researchers are accessing a territory close to the size of the US (a fact appreciated more than a century ago). I hope this discovery will result in greater support for research in the region. One day I am sure we will have a much clearer picture of what it is we are dealing with here.

Pinky promise.

Science Friday: DNA Testing

We’re very excited to bring you this weekly feature – Science Friday, a science talk show produced by NPR. Each week, a new video takes on a different on science topic, in an effort to bring an educated, balanced discussion to bear on the scientific issues at hand.

You may remember that we started this feature more than a year ago – but technical difficulties kept us from making it a regular appearance. Thanks to the fine folks at SciFri, however- I think we’ve got it figured out. Hopefully, we’ll be bringing you the science-y goodness every Friday from now on.

This week we follow two high school students from New York as they perform a DNA test on foods to see just what ingredients are in our everyday meals. They review if goat milk really comes from goats, the origin of caviar, and what exactly goes into New York City hot dogs.

Can’t see the video? Click here to view it.

The Eyes Have It: Evolutionary Development and DNA

Today’s guest blogger is Neal Immega. He has a Ph.D. in Paleontology and is a Master Docent here at HMNS. In his post below – originally printed in the Museum’s volunteer newsletter – Neal discusses Evolution Development and DNA.

Popular media crime shows, like CSI: Crime Scene Investigation, show amazing applications of DNA technology. For example, a person can be traced to a specific location by means of cells he left on a door knob.

A new science called “Evo-Devo,” shorthand for Evolutionary Development, can tell us even more amazing information. Evo-Devo techniques probe deeply into the structures of DNA to look at how DNA actually codes for the growth of body parts, telling us more about the animal kingdom than we ever dreamed possible. It shows genetic similarities between very different organisms and lets us understand how two organisms, like mice and men, can have DNA that is 85% similar and, yet, code for very different organisms.

We all know the basics of DNA molecules, where the genetic code is stored by a very long sequence of four proteins strung together in various arrangements. That is the easy part! What we need to
worry about is how these genes blueprint a living being. Geneticists, like Sean Carroll (whose popular books are listed in the references box), have discovered that the DNA code is made up of some large master programs that control things, such as eyes, and lots of very small programs (they call them switches) that control what kind of eye will be displayed.

Normal Fruit Fly
Image courtesy of The Exploratorium

Let’s confine ourselves to understanding and experimenting on simple life forms, such as fruit flies. To figure out which specific piece of DNA causes some feature to appear in a developing embryo, geneticists experimentally inactivate a segment of DNA, transplant the complete strand (including the inactivated segment) back into the egg, fertilize that egg, and then see what turns up missing. If that missing part is not vital for survival, the egg might even grow into an adult fly. Compare the drawings of a normal fly with the one below it where the master program for eyes has been deleted.

Eyeless Fruit Fly 
Image courtesy of The Exploratorium

Such experiments have found that the master program for making eyes can cause an eye to grow on a fly’s leg, body, antenna, or inside the body, depending on where it is placed on the DNA strand. Check out the drawing showing the results of moving the master program for legs to the site of the antenna. Note that the extra legs are fully formed but lack the neuron connections to the brain and so are not functional. (In the references box is a link to an electron microscope image of a real fruit fly that shows a mutation in which eyes replace antennae.)

Various mollusks (like clams, snails, and octopuses) grow eyes that vary in complexity from very simple sensitive pits to complex eyes that would compete well with human eyes. The EXACT SAME eye master program from a fruit fly can replace the eye master program for a squid, and it will grow a perfectly functional squid eye. You might be tempted to say that fruit flies and squids are cousins.

Fruit fly with extra legs
replacing the antennae 
Image courtesy of The Exploratorium

That is an amazing statement, but to take it even further, the same experiment with a mouse eye master program will grow fly eyes on flies and squid eyes on squids. They only differ by the small switch segments. These experiments establish a link between vertebrates and invertebrates that paleontologists are unlikely to find in the rock record. This also helps explain the amazing degree of structural similarity between mice and men—although many of the master programs are similar, the really critical parts of the DNA are the small switches that control the details.

Mollusks have just one master program that is controlled by different switches. Pectens, for example, have the most complex vision arrangement of any animal with three different types of eyes on its body. The DNA can be experimentally adjusted to grow any of these eyes anywhere on the body. Random mutations could thus cause novel arrangements, and survival would judge their fitness—evolution in action.

The switch concept explains how mice, chimps, and humans can have a similar number of genes. The switches control the result of the master programs. You can pick up any modern textbook and read that men and chimps have nearly identical genes. It is the switches that make us different and that provide the evolutionary means for dramatic changes, good and bad.

The fossil record is full of cases where a dramatic new species just appears. Paleontologists have often wondered if this was caused by a missing rock interval, by migration, or by rapid evolution. The concept of rapid evolution has often been discounted because it seemed to violate the incremental nature of evolution. We now can see how rapid evolution may just be a single point mutation in a switch. There are numerous biological examples where altering one protein is lethal, as in Tay-Sachs disease, or altering another might bear strongly on survival, as in changing
the color of hair from white to black.

Geneticists can now explain things in a way that profoundly affects how we think about evolution. Biologists and paleontologists have always wondered if evolution had to generate complex structures like eyes from scratch for each phylum. The reuse of master programs from very simple life forms through complex ones means that evolution can build on what went on
before. Critics of evolution often claim that eyes are too complex to have evolved. (The “half-an-eye-is-nogood” argument is derived from the first sentence of the Darwin quote in the box below.) Now, with Evo-Devo tools, we can see commonalities between the genetics of simple life forms and complex life forms– between clams and people.

The possibilities just became more complex.

Wyoming Dinosaur Center: http://www.wyodino.org/

Sean B. Carroll:
Endless Forms Most Beautiful: The New Science of Evo-Devo, (paperback) 2006
The Making of the Fittest: DNA and the Ultimate Forensic Record of Evolution,
(paperback) 2007
Remarkable Creatures: Epic Adventures in the Search for the Origins of Species, 2009

Lynn Helena Caporale:
Darwin in the Genome: Molecular Strategies in Biological Evolution, 2002

SEM (scanning electron microscope) photograph of eyes replacing antenna in a fruit fly by Naoum
Salame. http://1tv4.sl.pt

Fly Eye Genetics:
Renowned scientist Dr. Walter Gehring discusses master control genes and the evolution 
of the eye.

Darwin, 1859, The Origin of Species, http://darwin-online.org.uk/contents.html. In most editions, the quote appears on pp143-4.

We’ll, I’ll be a Monkey’s Uncle. Or an Orangutan’s.

Our Guest blogger today is Dr. Todd Disotell, a professor of anthropology and a molecular primatologist at New York University’s Center for the Study of Human Origins. He will be speaking at HMNS on Feb. 9 at 6:30 p.m. about new molecular analytical techniques and how mapping whole genome sequences has affected what we know about the past. In his blog below, Dr. Disotell debates a recently proposed theory that humans are more closely related to orangutans than chimpanzees – a theory he disagrees with.

Posing for the Camera
Creative Commons License photo credit: jimbowen0306

This past summer upon the publication of a paper by a colleague, I found myself at the intersection of a 25 year old hypothesis, the latest research in genomics and bioinformatics, and popular culture.  Jeffrey Schwartz of the University of Pittsburgh and his coauthor, John Grehan of the Buffalo Museum of Science published an updated version of their hypothesis that orangutans are more closely related to humans than are chimpanzees in the Journal of Biogeography.  This intrigued me because in my final year of graduate school, my advisors and I published one of the earliest papers utilizing DNA sequence data supporting the growing consensus that chimpanzees were our closest relative, followed by gorillas, and much more distantly orangutans.

Perhaps due to my working in New York City, a producer from the Daily Show with Jon Stewart called me at my office and wanted to know if I was willing to be interviewed about Schwartz’s hypothesis.  As a fan I readily agreed and correspondent John Oliver was dispatched to my laboratory to interview me.  During the course of the interview in which I stated that the hypothesis flew in the face of all known genetic evidence, I opined that I would at least get to write a counter paper and perhaps a counter-counter paper if Schwartz responded.  That got me thinking about newly available genomic data that was now available in various databases which had not been fully analyzed.

Confused chimp
Creative Commons License photo credit:
Tambako the Jaguar

I then downloaded the complete genome alignments that included human, chimpanzee, gorilla, orangutan, macaque, marmoset, lemur, and galago.  After writing a series of Python scripts (an open source computer programming language) to parse and reformat the masses of sequence data, I chose the first 1 million bases of each chromosome for which all of the above species were represented.  I then used well characterized statistical and analytical techniques to infer the evolutionary history of each DNA region.  Not surprising to me, the analysis of each region convincingly rejects the hypothesis that orangutans are more closely related to humans than are chimpanzees.  Furthermore, when these 30 million DNA bases are used to estimate the time of divergence between humans, chimpanzees, and orangutans using molecular clock techniques, the orangutan appears to have diverged at over twice the age chimpanzees have from humans.

These results are not at all surprising to the absolute majority of paleoanthropologists and evolutionary primatologists.  However, it is still worthwhile to occasionally revisit theories and hypotheses that we now take for granted when new data are generated and new analytical techniques are developed.  In this genomic age, as the genomes of more and more species and even individuals within species are being sequenced, a whole new class and scale of analyses can be carried out from the keyboard.

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Check out Dr. Disotell’s lecture, “Times Are a-Changin’: New Methods Tell A New Tale of Primate Evolution” at HMNS on Feb. 9 – get tickets here!