Prion protein essential for hematopoiesis

On the subject of why the PrP gene is evolving in humans, it is worth pointing to this new paper:

Prion protein is expressed on long-term repopulating hematopoietic stem cells and is important for their self-renewal
Cheng Cheng Zhang et al.
Although the wild-type prion protein (PrP) is abundant and widely expressed in various types of tissues and cells, its physiological function(s) remain unknown, and PrP knockout mice do not exhibit overt and undisputed phenotypes. Here we showed that PrP is expressed on the surface of several bone marrow cell populations successively enriched in long-term (LT) hematopoietic stem cells (HSCs) using flow cytometry analysis. Affinity purification of the PrP-positive and -negative fractions from these populations, followed by competitive bone marrow reconstitution assays, shows that all LT HSCs express PrP. HSCs from PrP-null bone marrow exhibited impaired self-renewal in serial transplantation of lethally irradiated mouse recipients both in the presence and absence of competitors. When treated with a cell cycle-specific myelotoxic agent, the animals reconstituted with PrP-null HSCs exhibit increased sensitivity to hematopoietic cell depletion. Ectopic expression of PrP in PrP-null bone marrow cells by retroviral infection rescued the defective hematopoietic engraftment during serial transplantation. Therefore, PrP is a marker for HSCs and supports their self-renewal.

I don't really have many thoughts about this function as a target of evolution in humans. It might make sense as a disease adaptation if the genetic changes affected expression or function in these HSCs. But the new variants don't seem to have an obvious disease-associated distribution -- for example, they're not predominantly African or South Asian like malaria defenses.

Still, the gene is expressed widely in different tissues and is probably very pleiotropic. Finding its recent selective pressures may be like threading a needle.