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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Signatures of Long-Term Balancing Selection in Human Genomes

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Bitarello, Barbara D. [1, 2] ; de Filippo, Cesare [2] ; Teixeira, Joao C. [2, 3] ; Schmidt, Joshua M. [2] ; Kleinert, Philip [2, 4] ; Meyer, Diogo [1] ; Andres, Aida M. [2, 5]
Total Authors: 7
[1] Univ Sao Paulo, Dept Genet & Evolutionary Biol, Sao Paulo - Brazil
[2] Max Planck Inst Evolutionary Anthropol, Dept Evolutionary Genet, Leipzig - Germany
[3] Inst Pasteur, Unit Human Evolutionary Genet, Paris - France
[4] Max Planck Inst Mol Genet, Computat Mol Biol Dept, Berlin - Germany
[5] UCL, UCL Genet Inst, Dept Genet Evolut & Environm, London - England
Total Affiliations: 5
Document type: Journal article
Source: GENOME BIOLOGY AND EVOLUTION; v. 10, n. 3, p. 939-955, MAR 2018.
Web of Science Citations: 12

Balancing selectionmaintains advantageous diversity in populations through variousmechanisms. Although extensively explored from a theoretical perspective, an empirical understanding of its prevalence and targets lags behind our knowledge of positive selection. Here, we describe the Non-central Deviation (NCD), a simple yet powerful statistic to detect long-term balancing selection (LTBS) that quantifies how close frequencies are to expectations under LTBS, and provides the basis for a neutrality test. NCD can be applied to a single locus or genomic data, and can be implemented considering only polymorphisms (NCD1) or also considering fixed differences with respect to an outgroup (NCD2) species. Incorporating fixed differences improves power, and NCD2 has higher power to detect LTBS in humans under different frequencies of the balanced allele(s) than other available methods. Applied to genome-wide data from African and European human populations, in both cases using chimpanzee as an outgroup, NCD2 shows that, albeit not prevalent, LTBS affects a sizable portion of the genome: similar to 0.6% of analyzed genomic windows and 0.8% of analyzed positions. Significant windows (P< 0.0001) contain 1.6% of SNPs in the genome, which disproportionally fall within exons and change protein sequence, but are not enriched in putatively regulatory sites. These windows overlap similar to 8% of the protein-coding genes, and these have larger number of transcripts than expected by chance even after controlling for gene length. Our catalog includes known targets of LTBS but a majority of them (90%) are novel. As expected, immune-related genes are among thosewith the strongest signatures, althoughmost candidates are involved in other biological functions, suggesting that LTBS potentially influences diverse human phenotypes. (AU)

FAPESP's process: 11/12500-2 - Maladaptation as a byproduct of adaptation: a genomic scale study
Grantee:Bárbara Domingues Bitarello
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 12/19563-2 - Detecting genes and genomic regions under balancing selection in the human genome
Grantee:Bárbara Domingues Bitarello
Support Opportunities: Scholarships abroad - Research Internship - Doctorate
FAPESP's process: 12/18010-0 - Balancing selection in the human genome: detection, causes and consequences
Grantee:Diogo Meyer
Support Opportunities: Regular Research Grants