Archaic Genes in Modern People?
dnaElizabeth Culotta

Science, Vol 308 (5721) 490-491 , 22 April 2005

Si un Homo sapiens procedente de Africa reemplazó a todos los homínidos anteriores a partir de hace unos 150.000 años, ¿cómo es posible la existencia del antiquísimo y asíatico Haplotipo X, prácticamente ausente en Africa, en muchas poblaciones del resto del mundo? Intrigante, ¿no os parece? *Resúmenes de la investigación original al final del artículo
If an African Homo sapiens replaced all the earlier hominids starting some 150.000 years ago, how is it possible the existence of the ancient Asian Haplotype X, virtually absent in Africa, in many populations in the rest of the world? Intriguing, don't you think?. *See abstracts of original research at the end of the article.

MILWAUKEE, WISCONSIN--About 1200 researchers gathered near the shores of Lake Michigan here from 5 to 9 April to discuss early Englishmen, the birth of modern humans, and Stone Age weapons.

In the past 15 years, a flood of genetic data has helped propel the Out of Africa theory into the leading explanation of modern human origins. DNA from mitochondria (mtDNA), the Y chromosome, and ancient humans each suggest that the ancestors of all living people arose in Africa some time after 200,000 years ago, swept out of their homeland, and replaced archaic humans around the globe without mixing with them. But at a genetics symposium, two independent groups presented data from the X chromosome hinting that modern humans interbred with other human species: The teams found possible traces of archaic hominids in our genes. "Just as the Y and mtDNA data seemed to have settled it, the new data revive the question [of interbreeding]," says Stanford University's Joanna Mountain, co-organizer of the symposium. "The controversy is not settled."

Geneticists Makoto Shimada and Jody Hey of Rutgers University in Piscataway, New Jersey, presented an intriguing haplotype--a set of genetic mutations inherited together--that appears to have ancient roots in Asia rather than Africa. Shimada sequenced a 10.1-kilobase noncoding region in 659 individuals from around the world. Overall, the genetic variations were most frequent in Africa, just as expected if our ancestors were a subset of ancient Africans who migrated out of that continent. But one rare variant, appropriately named haplotype X, appeared in nine individuals from Europe to Oceania but was entirely absent in Africa. Shimada estimated that the haplotype arose 1 million years ago, long before the modern human exodus from Africa. "Haplotype X is difficult to explain by the recent African origins model," says Shimada. "It's very old, it's rare, and it is widespread outside of Africa."

In independent work, geneticist Michael Hammer of the University of Arizona in Tucson offered a similar example. Hammer and postdoc Dan Garrigan identified a 2-million-year-old haplotype in the RRM2P4 region of the X chromosome that is common in East Asia but vanishingly rare in Africa. Their work, published 2 months ago in Molecular Biology and Evolution, raises the possibility that the haplotype arose in very ancient Asian populations, presumably of Homo erectus, an ancient human once found across Asia. "This is what you'd expect if you had introgression" between modern humans and H. erectus, Hammer said.

But at this point several other explanations are possible. Hey of Rutgers acknowledges, for example, that haplotype X may be present in Africa but was missed by spotty sampling in that continent. "Simply observing those [examples] is not sufficient to rule out one model or another," cautions Mountain. "What you need is 10 or 50 loci--one or two is not sufficient." Hammer, for one, thinks that these preliminary data do "speak to some archaic admixture. The few [loci] we've done so far are so suggestive that it gives me great excitement to continue sequencing more loci."


Shimada, M.K. and J. Hey (2005) History of modern human population structure inferred from the worldwide survey on Xp11.22 sequences. American Journal of Physical Anthropology, S40, pg. 190
For the study of human evolution, using DNA sequence data, long lengths are required because of low mutation rates. However long sequences have a higher probability that recombination has occurred in the region in the evolutionary history. On the other hand, microsatellite data have a high mutation rate but tend to have too much homoplasy. The limitations of different types of data are one reason why different studies have different conclusions regarding human evolutionary history. We sequenced a 10.1-kilobase pair region of the X chromosome, from 650 individuals from 50 populations. The sequenced region includes two microsatellites. The conjunction of sequence variation with tightly linked microsatellite variation allows each type of data to overcome the limitations of the other. We found very little evidence of recombination within the region. Most sequences are quite similar to one another, however three sequences differed from the others at an average of 28.6 substitutions. Assuming a molecular clock, and a human/chimpanzee divergence time of 6 million years, the estimated age of the base of the human sequences is 1.1 million years ago, whereas the estimated base of the tree excluding these divergent human sequences is 290,000 years ago. These divergent sequences were found in samples from the Middle East (Druze and Bedouin populations) and North Africa (Mozabite population). The pattern is suggestive of admixture between non-African Archaic humans and Modern Humans.

Hammer, M.F., D. Garrigan, J.A. Wilder, Z. Mobasher, T. Severson, S.B. Kingan (2005) Sequence data from the autosomes and X chromosome: Evidence from ancient admixture in the history of H. sapiens? American Journal of Physical Anthropology, S40, pg. 111.
A longstanding question in anthropology asks whether the history of our species is characterized by an expansion from an isolated panmictic population with complete replacement of archaic forms, or by admixture among divergent allotaxa. While mtDNA data support a recent and complete replacement model, nuclear loci present a more complicated picture. Two major problems associated with interpreting the heterogeneous patterns of variation observed at multiple nuclear loci are that sampling procedures vary across studies, and experimental designs generally lack statistical power to detect archaic admixture. We are undertaking a systematic survey of DNA sequence variation at 90 unlinked nuclear loci and developing a statistical framework (to be presented by Jeff Wall) to explicitly test the hypothesis of no admixture between modern and archaic forms, and for estimating the admixture ratio (if the null hypothesis is rejected). Our approach involves sequencing three windows of ~2 kb spanning ~16kb at each locus in a panel of 90 individuals from 6 populations. Preliminary data from two loci that show evidence of ancient admixture will be discussed. A gene tree constructed from sequence data at the first locus roots in East Asia and has a most recent common ancestor ~2 million YBP. The pattern of nucleotide variation at the second locus reveals two major lineages that have not undergone recombination for over 2 million years, and statistically rejects the null hypothesis of panmixia during the early ancestry of modern humans.

Daniel Garrigan, Zahra Mobasher, Tesa Severson, Jason A. Wilder and Michael F. Hammer (2005) Evidence for Archaic Asian Ancestry on the Human X Chromosome. Molecular Biology and Evolution Vol. 22  (2)
The human RRM2P4 pseudogene has a pattern of nucleotide polymorphism that is unlike any locus published to date. A gene tree constructed from a 2.4-kb fragment of the RRM2P4 locus sequenced in a sample of 41 worldwide humans clearly roots in East Asia and has a most-recent common ancestor approximately 2 Myr before present. The presence of this basal lineage exclusively in Asia results in higher nucleotide diversity among non-Africans than among Africans. A global survey of a single-nucleotide polymorphism that is diagnostic for the basal, Asian lineage in 570 individuals shows that it occurs at frequencies up to 53% in south China, whereas only one of 177 surveyed Africans carries this archaic lineage. We suggest that this ancient lineage is a remnant of introgressive hybridization between expanding anatomically modern humans emerging from Africa and archaic populations in Eurasia.