Directional and balancing selection on proprotein convertase subtilisin/kexin type 6 (PCSK6)
- Published
- Accepted
- Subject Areas
- Anthropology, Bioinformatics, Evolutionary Studies, Genomics
- Keywords
- PCSK6, balancing selection, directional selection, handedness, ancestral-susceptibility model
- Copyright
- © 2016 Kuderer et al.
- Licence
- This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ Preprints) and either DOI or URL of the article must be cited.
- Cite this article
- 2016. Directional and balancing selection on proprotein convertase subtilisin/kexin type 6 (PCSK6) PeerJ Preprints 4:e2141v1 https://doi.org/10.7287/peerj.preprints.2141v1
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.
Author Comment
This is a submission to PeerJ for review.
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
