Directional and balancing selection on proprotein convertase subtilisin/kexin type 6 (PCSK6)
Author and article information
Abstract
The selective pressures challenging the human population leave genetic signatures. This study was designed to detect positive and balancing selection on the proprotein convertase subtilisin/kexin type 6 (PCSK6) gene by four different approaches (FDIST, BayeScan, EHH, iHS). The outlier programs FDIST and BayeScan found 27 overlapping single nucleotide polymorphisms (SNPs) under selection, of which twelve are under strong positive directional selection and 15 under balancing selection. In the EHH analysis, all SNPs detected under positive selection show a slow decay of the derived extended haplotype. The integrated haplotype scores (iHS) for eight loci under positive selection were found to be larger than one. Based on these results, we provide a short overview of PCSK6-related mechanisms potentially associated with the detected positive or balancing selection patterns. Positive selection possibly reflects the key role of PCSK6 in tumorigenesis, in nociception, in rheumatoid arthritis and osteoarthritis, in the cardiovascular circulatory as well as in blood pressure regulation. Balancing selection acting on the PCSK6 locus might be explained by its involvement in vertebral left-right asymmetry and therefore in human handedness. Whereas until now the exact nature of the selective pressures acting on PCSK6 remained incompletely understood, the results of this study provide for the first time insights into the enzyme’s evolutionary significance owing to its functional manifoldness.
Cite this as
2016. Directional and balancing selection on proprotein convertase subtilisin/kexin type 6 (PCSK6) PeerJ Preprints 4:e2141v1 https://doi.org/10.7287/peerj.preprints.2141v1Author comment
This is a submission to PeerJ for review.
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Supplemental Information
EHH plots (columns: populations YRI, CEU, CHB and MXL) for the SNPs (rows) found by LOSITAN and Bayescan under positive selection
Figures are missing due to non-converging algorithm
Additional Information
Competing Interests
The authors declare that they have no competing interests.
Author Contributions
Sonja Kuderer conceived and designed the experiments, analyzed the data, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Martin Fieder conceived and designed the experiments, performed the experiments, analyzed the data, contributed reagents/materials/analysis tools, wrote the paper, prepared figures and/or tables, reviewed drafts of the paper.
Sylvia Kirchengast wrote the paper, reviewed drafts of the paper.
Data Deposition
The following information was supplied regarding data availability:
The raw data is not submitted as it is publicly accessible under http://www.1000genomes.org/.
Funding
The authors received no funding for this work.
