Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
PLoS Genet. 2011 Nov;7(11):e1002355. doi: 10.1371/journal.pgen.1002355. Epub 2011 Nov 3.

Signatures of environmental genetic adaptation pinpoint pathogens as the main selective pressure through human evolution.

Author information

  • 1Scientific Institute IRCCS E. Medea, Bioinformatic Lab, Bosisio Parini, Italy. matteo.fumagalli@bp.lnf.it

Erratum in

  • PLoS Genet. 2011 Nov;7(11). doi:10.1371/annotation/ca428083-dbcb-476a-956c-d7bb6e317cf7. Ferrer-Admettla, Anna [corrected to Ferrer-Admetlla, Anna].

Abstract

Previous genome-wide scans of positive natural selection in humans have identified a number of non-neutrally evolving genes that play important roles in skin pigmentation, metabolism, or immune function. Recent studies have also shown that a genome-wide pattern of local adaptation can be detected by identifying correlations between patterns of allele frequencies and environmental variables. Despite these observations, the degree to which natural selection is primarily driven by adaptation to local environments, and the role of pathogens or other ecological factors as selective agents, is still under debate. To address this issue, we correlated the spatial allele frequency distribution of a large sample of SNPs from 55 distinct human populations to a set of environmental factors that describe local geographical features such as climate, diet regimes, and pathogen loads. In concordance with previous studies, we detected a significant enrichment of genic SNPs, and particularly non-synonymous SNPs associated with local adaptation. Furthermore, we show that the diversity of the local pathogenic environment is the predominant driver of local adaptation, and that climate, at least as measured here, only plays a relatively minor role. While background demography by far makes the strongest contribution in explaining the genetic variance among populations, we detected about 100 genes which show an unexpectedly strong correlation between allele frequencies and pathogenic environment, after correcting for demography. Conversely, for diet regimes and climatic conditions, no genes show a similar correlation between the environmental factor and allele frequencies. This result is validated using low-coverage sequencing data for multiple populations. Among the loci targeted by pathogen-driven selection, we found an enrichment of genes associated to autoimmune diseases, such as celiac disease, type 1 diabetes, and multiples sclerosis, which lends credence to the hypothesis that some susceptibility alleles for autoimmune diseases may be maintained in human population due to past selective processes.

Comment in

PMID:
22072984
[PubMed - indexed for MEDLINE]
PMCID:
PMC3207877
Free PMC Article

Images from this publication.See all images (5)Free text

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Write to the Help Desk