Population differentiation of polygenic score predictions under stabilizing selection.

Given the many small-effect loci uncovered by genome-wide association studies (GWAS), polygenic scores have become central to genomic medicine, and have found application in diverse settings including evolutionary studies of adaptation. Despite their promise, polygenic scores have been found to suffer from limited portability across human populations. This at first seems in conflict with the observation that most common genetic variation is shared among populations.

Genomic basis of parallel adaptation varies with divergence in and its relatives.

Parallel adaptation provides valuable insight into the predictability of evolutionary change through replicated natural experiments. A steadily increasing number of studies have demonstrated genomic parallelism, yet the magnitude of this parallelism varies depending on whether populations, species, or genera are compared. This led us to hypothesize that the magnitude of genomic parallelism scales with genetic divergence between lineages, but whether this is the case and the underlying evolutionary processes remain unknown.

The timing of human adaptation from Neanderthal introgression.

Admixture has the potential to facilitate adaptation by providing alleles that are immediately adaptive in a new environment or by simply increasing the long-term reservoir of genetic diversity for future adaptation. A growing number of cases of adaptive introgression are being identified in species across the tree of life, however the timing of selection, and therefore the importance of the different evolutionary roles of admixture, is typically unknown. Here, we investigate the spatio-temporal history of selection favoring Neanderthal-introgressed alleles in modern human populations.

Adaptive introgression enables evolutionary rescue from extreme environmental pollution.

Radical environmental change that provokes population decline can impose constraints on the sources of genetic variation that may enable evolutionary rescue. Adaptive toxicant resistance has rapidly evolved in Gulf killifish () that occupy polluted habitats. We show that resistance scales with pollution level and negatively correlates with inducibility of aryl hydrocarbon receptor (AHR) signaling.

A Humanized Monoclonal Antibody against Heat Shock Protein 60 Suppresses Murine Arthritis and Colitis and Skews the Cytokine Balance toward an Anti-Inflammatory Response.

We have previously shown that naturally occurring as well as acquired Abs against the Mycobacterium tuberculosis heat shock protein (HSP)65 protect against the induction of murine autoimmune inflammatory arthritis. In the present work, we have studied the anti-inflammatory effect of prozumab, a humanized anti-HSP mAb in murine inflammatory arthritis and colitis, and its effects on cytokine secretion. Prozumab was shown to bind to HSP60, the highly conserved mammalian homolog of the bacterial protein, and it was found to be effective in protecting and suppressing autoimmune arthritis in the models of adjuvant arthritis and collagen-induced arthritis in rats and mice, respectively, as well as in acute hapten-mediated colitis and chronic, spontaneous colitis models.