Update: Update at the bottom.... In reference to the sequencing of the Neandertal genome, Kambiz at Anthropology.net states:
I have one little gripe with the New York Times article. Wade quotes a geneticist, Dr. Bruce Lahn saying there is, "evidence from the human genome suggests some interbreeding with an archaic species." Has he not read Paabo's paper 2004 PLoS paper, "No Evidence of Neandertal mtDNA Contribution to Early Modern Humans?" There is significant mtDNA evidence to stongly conclude that humans and Neandertals did not interbread directly.
I left a comment on that website, but I will elaborate a bit here. In reference to Bruce Lahn, he almost certainly has read that paper, but, 1) mtDNA can take you only so far. 2) Lahn is implicitly pushing a new paradigm in how we view human origins, a "genocentric" perspective, to borrow a phrase. To understand in detail about why mtDNA must be viewed with caution, read RPM's take down of its use in molecular ecology, or John Hawks' post which addresses the issue from a paleoanthropological angle. If you want it short and sweet: one locus isn't going to tell you the whole story, and that is more and more true as you push back into time. Reading the mtDNA lineage is reading the mtDNA lineage, not the sum totality of our evolutionary genomic history. But let's move past that issue. I am convinced by other data from other loci (autosomal & Y surveys) that the preponderance of our ancestry as modern human beings derives from Africa within the last 200-50 K years. What Lahn was alluding too, and was not particularly well articulated in the article, is that phylogeny and phenotype do not always track. Even if the vast majority of alleles are identical by descent from African populations, that does not mean that some of our alleles do not derive from "archaic" populations long resident in other regions of the world. What Lahn is pointing to is the possible persistence of locally favorable genetically coded traits as one population replaces another via enough interbreeding for the favored alleles to "jump" between demes. In a word: introgression. To comprehend this better a little baby-formalism is in order. The probability of fixation, the likelihood that an allele will reach ~100% in the population, is approximately 1/(2N) in the case of a neutral (neither favored nor unfavored) mutant, and 2s for a positively selected mutant. The relationship between these two values allows one to intuit the relative power of selection vs. drift within populations. Let's ignore drift, 1/(2N), and focus on selection, 2s. The variable s indicates the selection coefficient, roughly the proportional deviation above population mean fitness when an individual carries that allele against an average genetic background. In plain English, if you have allele x, you'll have more kids by increment y. A selection coefficient of 0.02 indicates a 2% increase in ftness. If a mutation occurred de novo within a large population (remember, let us ignore drift), then its probability of fixation would be 2 times its selection coefficient, so in the case specified earlier, 4%, or a 1 out of 25 chance that the mutant will sweep through the population from one mutational event and become "wild type." But what does this have to do with Neandertals and interbreeding? Everything. The baby-formalism above isn't tied to the functional-molecular genetic cases of de novo mutations within populations, but can be used to imagine circumstances where new alleles, operationally mutations, are introduced into the population from without. Concretely, a breeding event between indivduals from discrete populations where there is an exchange of disjoint alleles is equivalent to a mutational event. When the individuals go back to their populations of origin (imagine a woman returning impregnated from a sojourn), they will bring back the new genes. If they are favorable they may sweep through the population and fix, but this does not mean that the rest of the exogenous genome will be dragged along (though some might "hitchhike" and generate linkage disequilibrium, as you see in the HapMap), segregation and recombination will break apart associations so that the selectively favored locus will rise in frequency while other alien alleles will be effected by other neutral or selective dynamics independently. To extend the baby-formalism further, consider this case: 1) An allele that is present to fixation in Neandertals but not present in modern humans has a selection coefficient of 0.02 when introduced into the modern human genetic background 2) Neandertals and modern humans share a deme-deme border for tens of thousands of years 3) There were widely spaced intrebreeding events The probability of fixation of the new allele when it jumps from Neandertal to modern human is 4%. In other words, there is a 96% chance of extinction. Since the rare breeding events are spaced apart in time let's assume that for each event the extinction period is shorter than the next event. You can see where I'm going with this, the probability of a sequence of extinctions can be modeled as 0.96^n, where n represents the number of introductions. At 18 introductions of the mutation the expectation is less than 50% that fixation will not have occurred at least once (and of course biologically once it is fixed a new introduction is a moot point, and the genetic background will have shifted so that the allele is no longer favored against it. Independence is a little lie I introduced just to make the baby-formalism more infantile). In other words, genomes are dynamic, and they can "pick up" all sorts of local goodies through just a few breeding events. A clear and resounding objection to this is that humans and Neandertals were not interfertile. The reality is that the separation of the two populations was only 500,000 years BP, so it is almost certainly not true, tigers and lions are interfertile and they have been distinct for 2 million years. Another objection is that Neandertals looked too different. Again, the Watusi have had Twa (pygmy) queens, resulting in the matrimony of the tallest and shortest of human populations. Neandertals were distinctive looking, but I am skeptical that they were alien enough that one could never conceive of copulation with them. Additionally, we know humans have sex with animals all the time, or at least frequently enough that the dynamic I allude to above could result in allleles jumping populations. Finally, what's the payoff here, are there candidates for genes that could have jumped? Yes, there are, and one is mentioned in the article, at least implicitly, MC1R, which plays some role in melanin production. In Europeans this locus is extremely polymorphic, that is, it has a lot of diversity. This requires explaining, and some authors have posited negative frequency dependent selection, where low frequency traits hang around in the population because they are beneficial, but if they become too frequent they will be selected against. I won't hit on this, but address the issue for why this is introduced in the first place:
the coalescence, the common ancestors, for many of the MC1R alleles in Europe are very deep
, and some have estimated that the level of extant diversity would require 800,000 years to accumulate via neutral non-selective processes. What does this have to do with bumping Neandertal uglies? Neandertals separated from our own lineage 500,000 years ago, and emerged from archaic populations that have lived in Europe for as long as a million years. In other words, Neandertals had enough "time" to build up neutral alternative allelic variants which confered a selective advantange vis-a-vis new arrivals. What might have happened was simply that dark skinned Africans arrived on the scene, replaced the native Neandertals, but managed to pick up extremely beneficial locally adapted alleles for coloration from the predecessor population, who obviously had a long time to be optimized toward the local climatic regime. But this isn't what Lahn is pointing to in any case, the alleles are a lot more exciting than that. If you want to know, ask Evolgen, he's keeping the secret too :) Update: Just to be clear, my use of independent probabilities above was simply to suggest that the expectation of extinction decreases to triviality with only a few introductions of the allele.
