We also found significant signals of 4-Acetyl-1,1-dimethylpiperazinium iodide positive selection in genes that are related to lipid circulation and metabolism, such as SCP2 and CWH43 and in a genetic pathway related to cholesterol biosynthesis. Besides playing a role in nutrition, these genes could also be involved in immunological response, since cholesterol plays an important role in various infectious processes such as virus invasion and replication as well as in resistance against malaria. In this regard, Sabeti et al. already noticed a preponderance of genes related to the immune system in available genome-wide scans for positive selection. This prevalence was further confirmed by Williamson et al., L��pez Herr��ez et al., and Daub et al.. Besides the two genes mentioned above��SCP2 and CWH43, which have a possible role in immunity��the protein encoded by CCL28 modulates immunity to HIV infection and skin-related inflammatory diseases. Additionally, the selective pressure of this class of genes may also be important at the multi-genic level, since a network of 22 pathways involved in immune response presents signals of positive selection. After pruning, two of these pathways remain significant for more than one PS, namely ��PD-1 signaling�� and ��IL 12-mediated signaling events��. This indicates that they both have independently a strong selective signal, which would deserve further investigations for their role in adaptations to tropical environments. Another category of genes that frequently presents signals of positive selection is fertility, more specifically, spermatozoid development. In this regard, FKBP6, a male fertility factor, is found here to be potentially evolving under positive selection in our analyses, but this observation has to be taken with caution as this gene is not identified as an outlier in our supplementary analysis when Ameridian forest populations are compared to Zapotec instead of Pima. Heat-shock A 85380 dihydrochloride transcription factors, such as that encoded by HSF2, are activated by stress and respond to elevated temperatures. One of the consequences of inefficient thermoregulation is the increase of body temperature. The observed positive selection signals at SNPs found in this gene could be due to an adaptation to the tropics, initiating gene transcription in response to high body temperatures. Another study with African-, European- American, and Chinese populations also found a significant signal of positive selection in heat shock genes, suggesting that this category might have some importance in human adaptation to different environments worldwide. It is generally accepted that the pygmy phenotype might have evolved as an adaptation to life in dense tropical forests, to thermoregulation, and to food scarcity or as a by-product of selection for early onset of reproduction.