June 25, 2010

Y chromosome haplogroup I and disease-based selection

There have been occasional studies about natural selection acting on Y chromosome haplogroups, but this seems to one be one of the most convincing ones.

From the paper:
In this study, we aimed to refine our understanding of AIDS susceptibility associated with hg-I. We first analyzed AIDS progression differences between hg-I subhaplogroups and the phylogenetically closest haplogroup, haplogroup J (hg-J). Previously, we reported faster progression to AIDS outcomes in hg-I compared to the most common European haplogroup R, but did not analyze hg-J. As hg-I and hg-J are sister clades with similar time depths, and likely to have relatively closely related sequence organizations, it is interesting to see if the disease susceptibility is unique to hg-I or common among the hg-IJ clades.
The authors did identify that the AIDS susceptibility was Hg-I specific and was not shared by its sister clade, haplogroup J. From the paper:
There were significant differences between the hg-I subhaplogroups and hg-J samples for AIDS progression, where hg-I subhaplogroups depleted CD4+ T cells and progressed to AIDS 1993 and AIDS 1987 faster (Table 1). However, the faster AIDS progression signal (compared to the hg-J samples) was not significant for every individual hg-I subhaplogroup, probably due to small sample sizes resulting in lack of statistical power. When all hg-I subhaplogroups were combined (representing hg-I) and compared against hg-J, the significant AIDS progression differences were more evident (Pp0.02 for each AIDS end point; Table 1).

In contrast, when the hg-I subhaplogroup samples were compared against each other, the Cox analyses did not show a significant AIDS progression differences between them (Table 1).
One of the most interesting things about haplogroup I is its paucity outside Europe, in either West Asia or Siberia. The very strong genetic patterning of its sub-haplogroups in Europe is also quite noteworthy.

So, I am very willing to entertain the possibility that haplogroup I's distribution was shaped by rather recent evolutionary events that time has not been able to smooth out, and directional selection on this haplogroup seems like a very likely proposition.

The predominance of this haplogroup in the Lichtenstein cave remains from Bronze Age Germany is certainly not conclusive, but it may hint at a shift in frequency of this haplogroup in Europe. Hopefully more studies in both extant and ancient populations may provide data on this haplogroup's history.

J Hum Genet doi:10.1038/jhg.2010.77

Examination of disease-based selection, demographic history and population structure in European Y-chromosome haplogroup I.

Efe Sezgin et al.


We attempted to refine the understanding of an association of Y-chromosomal haplogroup I (hg-I) with enhanced AIDS progression that had been previously reported. First, we compared the progression phenotype between hg-I and its phylogenetically closest haplogroup J. Then, we took a candidate gene approach resequencing DDX3Y, a crucial autoimmunity gene, in hg-I and other common European Y-chromosome haplogroups looking for functional variants. We extended the genetic analyses to CD24L4 and compared and contrasted the roles of disease-based selection, demographic history and population structure shaping the contemporary genetic landscape of hg-I chromosomes. Our results confirmed and refined the AIDS progression signal to hg-I, though no gene variant was identified that can explain the disease association. Molecular evolutionary and genetic analyses of the examined loci suggested a unique evolutionary history in hg-I, probably shaped by complex interactions of selection, demographic history and high geographical differentiation leading to the formation of distinct hg-I subhaplogroups that today are associated with HIV/AIDS onset. Clearly, further studies on Y-chromosome candidate loci sequencing to discover functional variants and discern the roles of evolutionary factors are warranted.


  1. An odd study. I don't understand why one's haplogroup should be of any import to HIV/Aids progression.

    Without sounding bigoted haplogroup I is mainly European with minor frequencies in Anatolia, Levantine and North Africa. HIV/Aids is principally a problem of Western societies and in Africa, some parts of the underdeveloped world like Thailand. It just follows the there are more Europeans, and Americans of European origins who happen to be haplogroup I than haplogroup J, so there will be more reporting with that illness who belong to haplogroup I. Haplogroup J is mainly Middle Eastern, and a minority one in Europe in in the Mediterranean zone of Europe.

    Anyway, I hope the study is of some use to someone.

  2. "I don't understand why one's haplogroup should be of any import to HIV/Aids progression."

    And yet the correlation is there and presumably has some cause.

    If there is indeed a genetic cause, one can imagine that some disease that shared some mechanism with HIV/AIDS killed large numbers of people in one haplogroup but not the other, leaving the survivors of the affected haplogroup population with better biochemical defenses than the unaffected group. This would have had to have happened sometime after an IJ split, so probably sometime in the Holocene.

  3. Or how about the idea that 'the mechanism of action' of all diseases of 'crowding' such as the plague, tb, aids etc is similar and therefore those tribes with earlier experience of crowding (Farmers/pastoralists) would fare better against them than the hunter gatherers.

  4. In 2012 the authors published more papers showing that the genes in the I ydna affected heart disease,
    "Further analysis showed that men with haplogroup I showed downregulation of adaptive immunity as well as upregulation of inflammatory response pathways in their macrophages (immune system cells)"


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