RPM points me to a post at Salamander Candy which discusses the usefulness of neutral markers in conservation genetics. Obviously this complements my recent posts about introgression, and in fact, my last entry was a comment on a conservation genetic paper. Here is the important point from Salamander Candy:
The problem is, a growing body of evidence suggests that patterns of variation and divergence in adaptive traits are not well reflected by neutral markers...In the hypothetical species mentioned above, a small amount of gene flow between east and west would be enough to swap small numbers of alleles. This would hardly affect the divergent neutral genotypes at all, but newly introduced advantageous alleles would increase in frequency even if they were originally rare. For example, maybe all the northern ones have adaptations for cold temperatures and the southern ones are adapted to warmth. This pattern would not be reflected in the neutral markers.
Bingo! This is exactly what I've been alluding to, neutral variation does not necessarily reflect adaptively significant variation. Obviously this matters for conservation geneticists for deep philosophical reasons having to do with the raison detre of their field: the perpetuation of biodiversity.
Now, one issue with conservation genetics is that the primary reason they are focused on introgression is that they are attempting to assay populational variation accurately, and so the loci you select as your proxies matters a great deal. The cases I have been hypothesizing in relation to human evolution are situations where neutral variation, or disjoint neutral allelic distributions, may mask important selective sweeps constrained only to a few important, but significant, loci. In other words, though neutral regions of the Neandertal genome suggest little affinity with modern H. sapiens sapiens, that does not necessarily exclude the possibility that on a few significant loci there maybe more more similarity between Neandertals and some populations of H. sapiens sapiens (e.g., skin color through MC1R for Europeans). But what about the inverse scenario, that is, where neutral variation suggests a uniform population but there are loci which suggest hidden population structure driven by selective forces? Obviously this is one issue which is of interest to conservation geneticists, as local ecotypes may have emerged recently due to powerful selection on only a few traits. In these situations assays of neutral variation might underestimate the extent of diversity, and this has had relevance for public policy and the application of legislation designed to conserve biodiversity and protect "species."
But this issue of local ecotypes is not one that is restricted to animals only. It effects humans as well! This issue was brought to my attention by genetical anthropologist Henry Harpending several years ago. Harpending points out that both Basques and Bushmen do not seem to suggest genetic discontinuity from their neighbors. But the Bushmen do look very different from their Bantu neighbors, while the Basque are famous for their worldwide modal frequency of the Rh- allele. What's going on here?
Again, selection maybe at work. Consider the case of Bushmen. Their mtDNA does not suggest that they are very different from their Bantu neighbors, but their physical features are very distinct. How can it be that a neutral marker implies ancestral commonality while genes which code for appearance lead to sharply different physiognomies? Consider this thought experiment: imagine that two tribes, one of Bushmen, another of recently arrived Bantu, decide to "swap females." I am assuming maximal patriarchy here, even if it is not realistic, for illustrative purposes. The offspring of Bantu males would now all be genetically half-Bushmen while the offspring of Bushmen males would be genetically half Bantu. In fact, if you looked at mtDNA the children in the tribe of Bantu adult males would be Bushmen and vice versa! Now, because of sampling variance in segregation & independent assortment of genes the offspring in both tribes will exhibit a range in their gross appearance (assuming there is some overlap between the Bushmen and Bantu, if not, we'll have to push back the emergence of variance in the F2 generation). Though the expectation, the average, child in both tribes would look about the same, half-Bantu and half-Bushmen, both of the populations' F1 hybrid generations would exhibit a wide range in physique, favoring either Bantu or Bushmen. Now, imagine that fathers favor a particular appearance, and specifically, they favor their offspring who resemble their own physical type. In China the Hui Muslim ethnicity is known for speaking the local Chinese dialect and practicing Islam. Their origin likely lay during the influx of Central Asian officials and soldiers who arrived with the Mongol conquests, but in any case, over the centuries they have admixed with the local substrate. Nevertheless, I have read in the literature that when anthropologists visit Hui villages they are sometimes presented with an individual who looks far more Central Asian than East Asian, and the villagers will declare that this is a "true Hui," as this individual represents their idealized self-image. In other words, despite the reality that the Hui are now predominantly Chinese genetically through admixture they still emphasize a physical difference with their Han neighbors which has been diminished by generations of intermarriage (predominantly of Han women marrying into the Hui). If one assumes a situation of maximal patriarchy then the founding Bantu and Bushmen males could perpetuate social myths and legends of their idealized ancestors, who exhibited the "pure" Bushmen or Bantu look. In such a manner social selection could result in the sifting of the range of appearances for a particular physical type, and sexual selection could subsequently "fix" this type. And yet no matter the reality of phenotypic differences between the two populations, ancestrally informative neutral markers should, overall, show that both are genetically rather similar across the full genome!
Now, let us move to the Basques. First, you have to know a little about the problems with Rh incompatibility. The basics are this: a minority of European females are Rh-, which is a recessive phenotype, and these women have serious problems carrying Rh+ fetuses to term, increasing sharply after their first birth. Basques have the highest frequency of Rh- in the world. Because of their problems with pregancies during the pre-modern era other Spaniards looked askance at their sickliness, and there was even some talk of them being cursed by Satan. It seems likely that this Rh- frequency is a product of some sort of selective event, as a trait with such clear fitness implications can't just arise due to drift or mutation (see the equation for mutation-selection balance of a recessively expressed allele). But in any case, the Rh- status of many Basque females poses a problem for intermarriage with Rh+ peoples in the premodern era. Since so many Basque females are Rh-, the fitness of an Rh+ man would be lower vis-a-vis an Rh- negative male who married into the Basque community. Additionally, the fitness of a Rh+ homozygote would be lower than that of a Rh+ heterozygote (one copy of the functional allele). Nevertheless, we know intermarriage occurred, we see it in the genes. And yet the Rh- frequency of the Basques remains inordinately high. Could be the local selective force which originally allowed the rise in Rh- frequency? Perhaps. But here is another dynamic: consider the offspring of a "mixed marriage." If the outsider man was an Rh+ heterozygote, clearly fertilizations where the offspring was Rh- (because it received the loss of function copy) would be more fit from the get go, and much more likely to be carried to term. In the case of an Rh+ homozygote all of his fertilizations would result in Rh+ offspring, but, the first child would likely survive, and there is a non-trivial chance of subsequent survivals. But, the offspring themselves would marry within the Basque community, and again, the gauntlet of selection would favor fertilizations which resulted in Rh- offspring! But, this does not effect other loci, so in this way neutral alleles can leak between populations while selective weeds out Rh+. Even modest amounts of gene flow between populations tend to equilibrate neutral alleles, so you can have a Basque population which is ancestral "non-Basque," and yet still retain a stamp of the Rh- trait which has characterized their people for ages.
What does this mean in the big picture for humanity? Well, it means that we should be cautious about extrapolating from neutral variation. The evidence of powerful selective forces on the human genome within the last 10,000 years suggest that an analogy to "ecotypes" might be warranted for our species. Though we are relatively closely related our phenotypic variation should be a clue as the power of selection.
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Hi, Razib.
I know you are talking about a much wider topic but I will just comment on your speculations on Basques, on what I am more knowledgeable.
While Basques are very high in Rh- frequency, we are still 65% Rh+ (that's almost 2/3). Also high Rh- (in lower frequencies) is also common among all Europeans (with a tendency to decrease towards the East, pockets apart).
Apart of that, Basques did intermarriage with their inmediate neighbours on occasion but:
a- their inmediate neighbours are genetically very simmilar, including relatively high frequencies of Rh-
b- the intermarriage (or interbreeding - who says one has to get married to have children?) seems to have been relatively low, as genetics seem to show (at least to my eyes). In fact Basques seem a distilled or quite pure pocket of what Western Europeans were once long ago (before Neolithic and post-Neolithic migrations and invasions). Other almost as pure pockets are found among modern Celtic-speakers but also among Romance-speakers surrounding the Basque Country, specially Gascons.
For me it is quite obvious that the main barriers for intermarriage were cultural, linguistic and political. Some examples:
a- for almost all purposes, the Basque provinces can be considered virtually independent before the 19th century, and for the most part very rural and self-centered.
b- the lack of Celtic loanwords in Basque suggests strong animosity between Basques (and Aquitanians, etc.) and their Celtic neighbours in the Iron Age.
Even today the best way to earn the sympaties of Basque-speakers is to speak Basque yourself. Traditionally, even Humboldt (?) mentions that they looked at outsiders with strong reserve until you broke the ice speaking some Basque. Then the situation changed totally. Actually Basques define themselves as Euskaldunak/ok: Basque Speakers, while the rest of the planet are just Erdeldunak (maybe "babblers" or maybe "speakers of half-tongues"). Language was for sure a relative but strong barrier for milennia. Add to that different law and a strongly rural context of soft patriarchal character in which people usually married their neighbours from the same or a nearby village/town, often after a pregnacy happened in pre-marital relations.
You just can't take an isolated trait, anyhow common to all Europeans, even if in a more diluted density, and build around it supposed history of Basques. There's much more to Basque identity than just Rh- and, on the other hand, Basques are not that different from their Western European neighbours.
By the way, I have never heard of the supposed curse before. I know that we were relatively akin to witchery (ancestral religion mostly) but I never read that our neighbours treated us with such contempt; actually Castilians conceded us universal gentry status, and this was rationalized based in the antiquity of the "lineage"; also many Medieval monarchs had Basque wifes or mistresses without any known contempt (for instance, Abd al-Rhaman is Ummayad only by the pure paternal lineage, his mother and paternal grandmother were Basques). Can you reference your claim so I can illustrate myself on such an insteresting subject?
ref: a basque history of the world, page 91. the reference actually simply says the children were cursed, not cursed by satan (there are other references throughout the book to the devil, i must have confused the two). basques had purity of blood, no jews lived amongst the basques according to this book.
as for the genetics
a) yes, other europeans have rh-
b) yes, basques are not that different than other european groups
c) the key is the discrepancy between the frequency of rh- and neutral markers. that is, the latter tend to show a more gentle rate of change and exhibit less difference.
While I haven't read yet Kurlansky's famed book, I understand from reference that while being an excellent book for people that have little or no knowledge of Basque culture and history, it's not so good for people with greater knowledge, including most Basques. Anyhow, I guess Kurlansky documented his statement but I don't know on what.
The prohibition for Jews and Muslims (other than slaves, I think) to enter Basque territory only applied to part of it (Biscay, Gipuzkoa), already in the period of Castilian control. Other provinces had no such statutes and Jews were relatively well protected in Navarre while independent (there were a few pogroms but were clearly repressed by the state). It's not so simple as some have stated in the past, after all the Basque Country, specially after the 1199-1200 invasion by Castile of the west, was fragmented into several autonomous territories, each one with its own constitution and institutions (plus the territories no longer considered Basque that lost any self-rule). Most famous Basque Jew is the traveller Benjamin of Tudela.
the key is the discrepancy between the frequency of rh- and neutral markers. that is, the latter tend to show a more gentle rate of change and exhibit less difference
As far as I know Rh- clinal variation, at least in the case of Basques and our neighbours seems to correlate rather well with the other genetic differences/simmilitudes I have been able to spot in different studies (for instance it relates pretty well with Y chromosome haplotype frequency). It just seems to point, in my amateur opinion, to ancient (Western) Europeans being even more frequent in Rh- as they were surely more aboundant in R1b haplogroup, that is: much more homogeneous genetically.
Can you refer me to a study where such a discrepancy is highlighted? Thanks.
much more homogeneous genetically
are you are implying here that stochastic factors, drift, could case here? the power of selection vs. drift can intuited in the following manner:
1/(2 * effective populatio) = probability of fixation for a neutral allele
2 * selection coefficient = the probability of fixation of a positively selected allele
in other words, if you have a selection coefficient of .01, 1% greater for an allele tha the background men fitness, the effective population needs to be 25 individuals or less for drift to be a greater factor in the evolutionary dynamics (1/(2* 25)). i use this simple model to show you that selection has to be very weak, nearly zero, for drift to be more powerful. is Rh- a neutral allele? i doubt it, it has profound physiological and developmental implications, and other blood factors (ABO) have been strongly correlated with physiological processes as well. in other words, i don't know anyone who believes that the blood groups distribute the way they do purely based on demographic history, as opposed to selective forces. even if the western europeans in the iberian refugia went through a population bottleneck and then expanded with a nearly 100% fixation of Rh-, over the last 10,000 years intermarriage with Rh+ positive populations from the east should have swept this away, seeing as how Rh+ seems selectively favored.
i will post henry's paper when his site comes back up...that is the initial reason i didn't provide the link to the orginal paper.
google cache of the paper. follow the references (it is a little dated since archeogenetics always produces new papers).
Thanks for the link. It's an interesting paper but why does they exclude so sharply that, for our case, European colonization by modern humans could have been caused by a very small group of people rapidly growing in a relatively wealthy landscape where they had apparent technological and maybe intelectual advantage over Neanders?
Their way of treating the process of inmigration into Basque-speaking societies seems a little ignorant of the prehistory (archaeology) behind. For instance the first IEs seem to have arrived to near the Basque area only in the last milennium BCE and these (probably Celtic) newcomers weren't welcomed if we follow the linguistic reasoning. So the input (Neolithic isolates apart) only started actually in Roman times but was surely interrupted again soon after only to be restarted in the High Middle Ages. So while he ponders 250 generations, I can only count about 100 at most. And most of them were from nearby Northern Spain or Southern France, where the genome is most simmilar.
I have to read that more carefully but I'm under the impression that his questionable assumptions are what cause his conclussions.
Regarding your first comment, Rh- is a negative trait that is probably selected against but rather weakly. The first newborn is almost always unaffected and the mother is only sensitized in about 13% of cases (from Wikipedia - Rh disease). It is a big individual problem when it happens but it does not happen necessarily and the first child is almost always free from trouble. Considering that the Franco-Cantabrian region was surely the best place to live in Ice Age Europe and that anyhow the "tribe" that settled it started already with a huge Rh- density (by founder effect, in my understanding), it should not have been so significatively selected against, as it is not significatively selected against today (or "the day before" when modern medical tech wasn't still available to treat or prevent the disease).
Also please ponder that an Rh- Basque woman is very likely to have Rh- children, also unaffected when the mother may have been sensitized, because her husband would quite probably be either Rh- or Rh+ heterozygote. Only with an Rh+ homozygote husband the threat of lacking healthy descendancy after the first born icreases up to 13%. If you look at it carefully it may be well seen as an in-built biological "defense" against Rh+ homozygote men (rather weak anyhow), statistically against foreigners. This could well compensate against your and your colleagues' model and even favor the concentration of Rh- alelles in highly dense Rh- areas as the Basque Country and others.
I think I have spotted several reasons why your colleague's model can be questioned. It's not as simple as saying Rh- is a problem and is selected against... it may be but it can also act as a filter against Rh+ males' descendance, and anyhow it's effect (considering the many other health threats that may have affected Basque and even overall European people through prehistory and history) seems quite small.
You are better than me at the maths of biology and statistics, so, if you feel such task interesting, please go ahead and try to claculate a corrected effect with my objections in it. Intuitively I feel pretty sure the selective effect would be minimal and maybe even null (as pro-Rh+ and pro-Rh- pressures seem to compensate each other for high densities of Rh-).
If you look at it carefully it may be well seen as an in-built biological "defense" against Rh+ homozygote men (rather weak anyhow), statistically against foreigners. This could well compensate against your and your colleagues' model and even favor the concentration of Rh- alelles in highly dense Rh- areas as the Basque Country and others.
this exactly his model.
this exactly his model
Uh!
Then it seems I was missing something. Sorry.
Yes - I was missing something indeed! Harpending and Eller are suggesting that the whole Basque genome (y-chr haplogroup, I assume) has been replaced by mere dropping of isolated inmigrants. That just makes no sense!
LOL - That's an even more far fetched theory than anything I read before. It's a total nonsense.
Just to explain my previous objection: Eastern inmigrants were not purebreeds: they were surely mostly very simmilar to Basques. As peoples moved westward through centuries and milennia they mixed with locals becoming more and more like Basques in the proccess. That's why the R1b haplogroup, once surely dominant in most of Europe, becomes less dense towards the East. But inmigrants were always few and locals many, there's no way that they could have done anything else than diluting themselves, becoming more and more Western Europeans as they mixed with the locals. Of 10 inmigrants arriving 5 or more had R1b. There was very limited inmigration and intermarriage anyhow all the time, so it's impossible that such thing happened.
Western Europeans are descendants of Easterners ("Neolithics" and IEs) only in a very limited ammount. They may speak IE languages now but they are not very IE by blood. That's evident and most markers are coincident. As I said before R1b and Rh- for instance are very simmilar in their patterns of distribution.
And, in the end, the more I look at it, I don't see that Rh- is such a selective problem. Just look at Africa with a much larger selective history and still relatively aboundant in that blood type. The extreme cases of West and East Eurasia can only be explained by founder effect.
luis,
i'm not particularly interested in the details of this argument (i.e, basques), but i refer you to this website, population genetic notes. the mathematics is no more difficult than algebra. i am not responding to your comments at this point because they aren't precise enough for me to know whether i disagree or not.