Balancing Selection on a Regulatory Region Exhibiting Ancient Variation That Predates Human–Neandertal Divergence
View/ Open
Author
Mulder, Lubbertus C. F.
Iskow, Rebecca C.
Austermann, Christian
Scharer, Christopher D.
Boss, Jeremy M.
Stranger, Barbara
Simon, Viviana
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1371/journal.pgen.1003404Metadata
Show full item recordCitation
Gokcumen, Omer, Qihui Zhu, Lubbertus C. F. Mulder, Rebecca C. Iskow, Christian Austermann, Christopher D. Scharer, Towfique Raj, et al. 2013. Balancing selection on a regulatory region exhibiting ancient variation that predates human–neandertal divergence. PLoS Genetics 9(4): e1003404.Abstract
Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup) aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs) across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (p<10−15). Moreover, the nucleotide diversity at this locus is higher in Eurasians than in Africans. These results mimic signatures of recent Neandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003) and positive Tajima's D (p = 0.00285) statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human–Neandertal divergence and is evolving under balancing selection, especially among European populations.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623772/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:11235975
Collections
- HMS Scholarly Articles [17917]
- SPH Scholarly Articles [6362]
Contact administrator regarding this item (to report mistakes or request changes)