Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Nov 20;4(11):e7927.
doi: 10.1371/journal.pone.0007927.

Genome-wide scan for signatures of human population differentiation and their relationship with natural selection, functional pathways and diseases

Roberto Amato  1 , Michele Pinelli, Antonella Monticelli, Davide Marino, Gennaro Miele, Sergio Cocozza
Affiliations

Genome-wide scan for signatures of human population differentiation and their relationship with natural selection, functional pathways and diseases

Roberto Amato et al. PLoS One. .

Abstract

Genetic differences both between individuals and populations are studied for their evolutionary relevance and for their potential medical applications. Most of the genetic differentiation among populations are caused by random drift that should affect all loci across the genome in a similar manner. When a locus shows extraordinary high or low levels of population differentiation, this may be interpreted as evidence for natural selection. The most used measure of population differentiation was devised by Wright and is known as fixation index, or F(ST). We performed a genome-wide estimation of F(ST) on about 4 millions of SNPs from HapMap project data. We demonstrated a heterogeneous distribution of F(ST) values between autosomes and heterochromosomes. When we compared the F(ST) values obtained in this study with another evolutionary measure obtained by comparative interspecific approach, we found that genes under positive selection appeared to show low levels of population differentiation. We applied a gene set approach, widely used for microarray data analysis, to detect functional pathways under selection. We found that one pathway related to antigen processing and presentation showed low levels of F(ST), while several pathways related to cell signalling, growth and morphogenesis showed high F(ST) values. Finally, we detected a signature of selection within genes associated with human complex diseases. These results can help to identify which process occurred during human evolution and adaptation to different environments. They also support the hypothesis that common diseases could have a genetic background shaped by human evolution.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Distribution of FST values across chromosomes.
For each chromosome, the box length is the interquartile range while the horizontal line inside it is the value of the median. The whiskers extend to the most extreme data point <1.5 times the interquartile range from the box. Extremes of the notches represents 95% confidence interval of the median.
Figure 2
Figure 2. Correlation between FST values.
The correlation is calculated, for each chromosome, for all pairs of SNPs separated by a fixed number of intervening SNPs. Black line shows mean value and 2σ error bars of the correlation of SNPs belonging to autosomal chromosomes. Red line shows correlation among X-linked SNPs.
Figure 3
Figure 3. Mean FST value of genes with and without interspecific evidence of positive selection.
Genes were grouped according to the strength of evidence of their positive selection across six species . Vertical bars represent 95% confidence interval.
Figure 4
Figure 4. Leading edge genes of the high FST enriched KEGG pathways identified by GSEA.
Genes are indicated by gene symbols. Red box marks the presence of that gene, as leading edge gene, in that pathway.
Figure 5
Figure 5. Mean FST value of genes associated to complex diseases.
Genes found positively associated with complex diseases according to the Genetic Association Database are compared with the remaining ones. Vertical bars represent 95% confidence interval.
Figure 6
Figure 6. Mean FST values of genes in different disease classes.
Genes were grouped according to the diseases classification of Genetic Association Database. Vertical bars represent 95% confidence interval. Horizontal solid and dashed lines represent mean value and 95% confidence interval of the set of non associated genes.
See this image and copyright information in PMC

References

    1. Cavalli-Sforza LL, Menozzi P, Piazza A. Princeton: Princeton University Press; 1996. The History and Geography of Human Genes.
    1. Barbujani G, Goldstein DB. Africans and Asians abroad: genetic diversity in Europe. Annu Rev Genomics Hum Genet. 2004;5:119–150. doi: 10.1146/annurev.genom.5.061903.180021. - DOI - PubMed
    1. Kimura M. Cambridge: Cambridge University Press; 1985. The Neutral Theory of Molecular Evolution.
    1. Akey JM, Zhang G, Zhang K, Jin L, Shriver MD. Interrogating a high-density SNP map for signatures of natural selection. Genome Res. 2002;12:1805–1814. doi: 10.1101/gr.631202. - DOI - PMC - PubMed
    1. Bamshad M, Wooding SP. Signatures of natural selection in the human genome. Nat Rev Genet. 2003;4:99–111. doi: 10.1038/nrg999. - DOI - PubMed

Publication types