In the world of genetic anthropology, mitochondrial DNA and the Y-chromosome are the major players.  They are regions of our genome scientists use most frequently when tracing both ancient and historical human migrations, and are an important tool for genealogists using DNA to piece together their family trees.

But another part of the human genome has recently started to prove itself as a window into our species’ past: the X-chromosome.  Like both the mtDNA and the Y-chromosome, the X is passed from parents to children in such a way that scientists can use it to to trace the deep ancestry of our species. But it is only recently that the X-chromosome has been used this way, and some of the early research has been rather inconsistent.

Now, the authors of a paper published in this week’s Nature Genetics believe they have perfected a way of using the X-chromosome to unravel details about the initial migration of humans out of Africa tens of thousands of years ago. Their results suggest that more men than women were involved in the exodus that initiated the peopling of the entire globe.

One of the reasons analysis of the X-chromosome has not proven straightforward compared to the mtDNA or the Y-chromosome is that the way the X is passed down from one generation to the next differs depending on the sex of the child. Fathers pass on their X-chromosomes to their daughters, but not their sons, while mothers pass one X-chromosome to their children of both sexes. So while any person’s X-chromosome came down to them along a specific lineage — just like their Y-chromosome and mtDNA — that path is impossible to trace.

But the X-chromosome does have one distinctive quality. Since men have one and women have two, any population with a 50/50 sex ratio will have three X chromosomes for every four of the 22 paired chromosomes. And that means that all other things being equal, genetic diversity on the X-chromosome should be about three-quarters as much as it is on the non-sex chromosomes.

To see if all has been equal in the history of the human species, researchers from Harvard, the Broad Institute and the National Human Genome Research Institute analyzed the genotypes of people from around the globe and looked for differences among the populations of Africa, Europe and East Asia. Though they found the expected 75% X-chromosome diversity ratio within Africans, there was considerably less diversity among European and East Asians on the X compared to their 22 non-sex chromosomes.

What could all this mean?  First of all, a decrease in genetic variation is usually a sign of decreased population size.  Because it shows up in East Asians and Europeans but not Africans, the authors believe the decreased variation is a signal of a population bottleneck that occurred after humans left Africa for the first time nearly 60,000 years ago — but before the non-African populations diverged from each other.

But the decreased genetic variation only seems to show up on the X-chromosome.  This, the authors speculate, may be due to some sort of sex-biased migration.  In other words, when humans first ventured outside of Africa and into Europe and Asia, there may have been more men on the move than women.  Scientists have long observed the same phenomenon when comparing the Y-chromosome to mtDNA; now researchers are seeing the same phenomenon here, with the X.

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The place of Neanderthals in the story of human evolution has been hotly debated for decades.  A distant cousin to our species, Neanderthals had already been in Europe over 250,000 years when Homo sapiens first arrived there 35,000 years ago.

Often called Cro-Magnoids, these first Europeans are believed by many scientists to have out-competed the Neanderthals, gradually driving them to extinction. The alternative theory, that Neanderthals and early humans are more closely related and may have even interbred upon meeting, is less popular, though it hasn’t yet been ruled out.  In order to resolve this debate, scientists have turned to genetics and methods of ancient DNA analysis to help them answer the questions surrounding the relationships between Neanderthals and Cro-Magnoids.

However, the practice of extracting and analyzing ancient DNA remains tricky and fraught with skepticism.  One of the main problems is contamination – anyone who touches fossilized remains runs the risk of contaminating it with his or her own DNA.  So how can we tell if scientists are analyzing the right DNA? A new study in this week’s PLOS One attempts to rectify the contamination problem in a novel way by analyzing the DNA of everyone who touched a fossil for comparison in order to rule out contamination. It will also help us better understand the genetic connection between Cro-Magnoids and Neanderthals.

The Italian team, led by David Caramelli, analyzed DNA from a 28,000-year-old Homo sapiens Cro-Magnoid individual found in Piglacci Cave in Italy.  They also analyzed the DNA of everyone who had touched the remains since its 2003 discovery.  What they found was that the Cro-Magnoid individual was genetically similar to most modern Europeans.  The Cro-Magnoid DNA was also distinct from the researchers’ DNA sequences, showing that none of them had contaminated the sample. When the DNA of the Piglacci Cro-Magnoid individual was compared to previous analyses of Neanderthal DNA, the researchers found that the Cro-Magnoid individual has much more in common genetically with modern European humans than with Neanderthals. These results are important for several reasons.

• First, this is one of the first studies to have obtained a reliable and contaminant-free sample of DNA from a 28,000-year-old Cro-Magnoid.  It will hopefully satisfy the skeptics who had claimed contamination will always be a possibility.
• Second, the genetic similarity of the Cro-Magnoid to modern Europeans, combined with its lack of similarity to Neanderthals, helps solidify the theory that the two ancient groups were not closely related.  Previous studies comparing Neanderthal DNA to modern human DNA have also turned up no genetic similarity.
• Third, the body of evidence now shows that Neanderthals didn’t contribute any DNA to the Cro-Magnoid OR modern human gene pool. Indeed, Caramelli and his colleagues point out that “the burden of proof is now on those who maintain that Neanderthals might have contributed to the modern gene pool.”

Together, the current scientific evidence suggests that instead of merging with Cro-Magnoids Neanderthals must have simply died out, unable to compete with the Cro-Magnoids’ superior technology and greater population size.  The archaeological record shows Neanderthals becoming less and less prevalent around 35,000 years ago, and by 30,000 years ago, they disappear completely.

After their rivals’ disappearance, Cro-Magnoid humans would have to cope with hardships of their own, as the Last Ice Age was approaching its peak.  They would be relegated to the southern fringes of Europe for 5,000 years, awaiting the warming temperatures that would allow them to repopulate the continent.

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Neanderthal and Homo sapiens skeletons side by side. The thicker femurs, different eye sockets and barrel-shaped chest of our distant relatives are prominent in this comparison.

Mining the past: The Neanderthal Genome Project
The first invited speaker at the SMBE 2008 conference was Svante Pääbo of the Max Planck Institute for Anthropology in Germany. Pääbo and colleagues continue their incredible project to sequence the Neanderthal genome. Neanderthals are especially interesting in understanding our own history; they were another animal that walked upright, hunted with weapons, used clothes, and had culture, traits we consider very “human.” Pääbo presented some new findings that may change the way we think about our own history and that of our distant cousins, who went extinct around 25,000 years ago.

So far, the project has sequenced more than 3 billion Neanderthal DNA base pairs. The figure sounds impressive, and it is. However, sequencing ancient DNA is subject to contamination and in fact more than 99% of the DNA Paabo’s group extracts from Neanderthal bones is from bacteria, fungi or other organisms – including modern humans.

Scientists have debated for decades whether Neanderthals and humans interbred. So far, the Neanderthal genome does not show any evidence of having human ancestry. But the recent split between humans and Neanderthals has resulted in some sharing of genetic material between the species. That is, some people may share versions of SNPs with Neanderthals, but this sharing traces to a common ancestor who lived before the two species split about 800,000 years ago.

One especially interesting finding by Paabo’s group was in the so-called “language gene,” FOXP2. Humans have a very different version of FOXP2 than most other mammals, birds, and reptiles. Rare deletions in the gene cause people to have trouble with speaking and comprehension, providing support that the gene is important for language. Interestingly, other verbal mammals also have changes in FOXP2.
Scientists had thought the “human” version of FOXP2 arose within the last 200,000 years, since the origin of Homo sapiens and long after the human lineage split from Neanderthals. However, it turns out Neanderthals share the human version of FOXP2. These results indicate that something else happened in human history to make FOXP2 appear younger than it really is; and that this may not be related to the unique version of the gene shared by humans and Neanderthals.
So, is FOXP2 the gene that makes us unique from other animals? No. But could it still have played an important part in our own history? Probably. Just one of the many mysteries that evolutionary geneticists hope to answer.

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