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你有远古种系血统吗?HLA-B*73基因频度

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发表于 2013-3-5 15:43 | 显示全部楼层 |阅读模式
研究者john hawks推测可能与尼安德特人的西支有关。

HLA B*7301 frequenciesfreqref.Population(%)[4]Parsi (Karachi, Pakistan)4.9[4]United Arab Emirates2.0[4]Italy2.0[4]Seri (Sonora, Mexico)1.5[4]P'urhépecha (Michoacán, Mexico)1.5[4]Jews (Israel) (*2 studies)1.2[4]Beti (Cameroon)1.1[4]Casablanca (Morocco)0.9[4]Tbilisi (Georgia)0.9[4]Mossi (Burkina Faso)0.9[4]Bulgaria0.9[4]Sudanese0.8[4]Tuva (Russia) (2)0.8[4]Oman0.8[4]Bamileke (Cameroon)0.6[4]Pathan (Pakistan)0.5[4]Khalkha (Mongolia)0.5[4]Druse Arabs (Israel)0.5[4]Baloch (Iran)0.5[4]Manchester (England)0.5[4]Algeria (1)0.5[4]Turkey0.4[4]Amman (Jordan)0.3[4]Shona (Harare, Zimbabwe)0.2[4]Republic of Macedonia0.2[4]Nandi (Kenya)0.2[4]Luo (Kenya)0.2[4]Campania (Italy)0.2[4]Greece0.2


The curious case of HLA-B*73If I agree that the results of this paper are pretty likely, why am I still cautious? Well, the most confusing thing in this paper is an allele described in great detail that they didn't find in the archaic genomes. And I know from experience that not finding things is a pretty common occurrence when we go looking for odd things that might have come from Neandertals.
There's a detective story here, that probably explains the initial interest of this group in the Neandertal genome, but that just didn't pan out in their search through the archaic genomes. The allele is HLA-B*73.
Parham and colleagues [3] first characterized this allele, which is remarkably different from other HLA-Balleles. Homologs of HLA-B*73 are present in living apes, suggesting that the different human alleles originated before we diverged from gorillas. The retention of such an ancient allele in humans isn't a surprise in the HLA system, because many very divergent alleles have been kept in the population across evolutionary time by balancing selection. What's a bit surprising about HLA-B*73 is its limited diversity in living people. It appears to have persisted in humans throughout our evolution, but people today who carry the allele have very similar sequences, and it is nearly always linked to one single allele at the nearby gene, HLA-C (HLA-C*15). Also, the allele is very rare inside Africa and reaches its highest frequency in West Asia., where it occurs in only 4.5 percent of people. Because of this strange pattern, Parham and colleagues suggested that the allele may have been inherited from Neandertals.
When I was in graduate school working on modern human origins, I took a special interest in genes that had this pattern of variation. HLA-B*73 was not the only one, there are others.
The variation of the HLA-B*73 allele and its association with HLA-C*15 correspond very well to the predictions we presented in our paper on identifying introgression from archaic humans [2]. It's a highly divergent allele in humans compared to others, and it appears not to have recombined much with nearby genes, suggesting it was sequestered in another population through much of the diversification of present-day HLA alleles. But the HLA system is actually a rotten place to look for this kind of evidence, because there are many, many instances where ancient alleles have been retained in human populations by balancing selection. As we pointed out in 2008, a deep root to the gene tree and a rarity of recombination can be good evidence of introgression, but balancing selection and inhibitions to recombination are alternatives to introgression for explaining this pattern of variation.
There's no necessary contradiction between the two processes, and ancient DNA in this case could establish that the allele was both under selection and came from archaic humans. The problem: they didn't find the allele in the archaic genomes.
So why did they spend so much time in this paper discussing this allele? My guess is that they were surprised not to find it. But they did find HLA-C*15 in the Denisova genome, which is often linked to HLA-B*73 in living people who carry it. That makes for an indirect argument:
C*12:02 and C*15 were formed before the Out-of-Africa migration (Fig. 2H and fig. S15) and exhibit much higher haplotype diversity in Asia than in Africa (fig. S16), contrasting with the usually higher African genetic diversity (20). These properties fit with C*12:02 and C*15 having been introduced to modern humans through admixture with Denisovans in west Asia, with later spreading to Africa (21, 22) (Fig. 1F and fig. S11 for C*15). Given our minimal sampling of the Denisovan population it is remarkable that C*15:05 and C*12:02 are the two modern HLA-C alleles in strongest LD with B*73 (Fig. 1E). Although B*73 was not carried by the Denisovan individual studied, the presence of these two associated HLA-C alleles provide strong circumstantial evidence that B*73 was passed from Denisovans to modern humans.
I would go one simpler: Given that HLA-B*73 is most common today in West Asia, I suspect it came from West Asian Neandertals. There's no reason why the HLA genes of European Neandertals should have been identical to West Asian Neandertals. Today's Europeans are different from today's West Asians in the frequencies of these alleles, so why not in the past as well? For that matter, we really only have two alleles from European Neandertals for HLA-B (since the paper finds that
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