Limits...
Human gephyrin is encompassed within giant functional noncoding yin-yang sequences.

Climer S, Templeton AR, Zhang W - Nat Commun (2015)

Bottom Line: Its specific function is intricately regulated and its aberrant activities have been observed for a number of human diseases.The gephyrin yin-yang pair consists of 284 divergent nucleotide states and both variants vary drastically from their mutual ancestral haplotype, suggesting rapid evolution.This discovery holds potential to deepen our understanding of variable human-specific regulation of gephyrin while providing clues for rapid evolutionary events and allelic migrations buried within human history.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Engineering, Washington University, St Louis, Missouri 63130, USA.

ABSTRACT
Gephyrin is a highly conserved gene that is vital for the organization of proteins at inhibitory receptors, molybdenum cofactor biosynthesis and other diverse functions. Its specific function is intricately regulated and its aberrant activities have been observed for a number of human diseases. Here we report a remarkable yin-yang haplotype pattern encompassing gephyrin. Yin-yang haplotypes arise when a stretch of DNA evolves to present two disparate forms that bear differing states for nucleotide variations along their lengths. The gephyrin yin-yang pair consists of 284 divergent nucleotide states and both variants vary drastically from their mutual ancestral haplotype, suggesting rapid evolution. Several independent lines of evidence indicate strong positive selection on the region and suggest these high-frequency haplotypes represent two distinct functional mechanisms. This discovery holds potential to deepen our understanding of variable human-specific regulation of gephyrin while providing clues for rapid evolutionary events and allelic migrations buried within human history.

No MeSH data available.


Related in: MedlinePlus

Recombination ratesShown are the recombination rates provided by the HapMap Consortium for the yin-yang region. These rates were computed using the CEU, CHB, JPT, and YRI population data. All of these positions are within the yin-yang region and the recombination rate of 9.2 cM Mb−1 was estimated at rs10133120 in the 5′ end of gephyrin.
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Figure 6: Recombination ratesShown are the recombination rates provided by the HapMap Consortium for the yin-yang region. These rates were computed using the CEU, CHB, JPT, and YRI population data. All of these positions are within the yin-yang region and the recombination rate of 9.2 cM Mb−1 was estimated at rs10133120 in the 5′ end of gephyrin.

Mentions: Third, the unusual recombination patterns in this region support selection favoring the yin and yang haplotypes. A close examination of Figs. 1, 2, and 3 suggests that recombinants comprised of both a yin and yang parental haplotype are generally rare, particularly within gephyrin and upstream from this gene. Such a recombinant would appear as a horizontal bar comprised of blocks that are two different colors in Fig. 1. As shown in Fig. 2, nine of the 340 CHB and JPT haplotypes have between 10% and 90% yin/yang compositions; six of these represent yin-yang recombinants and three represent intermediate yin or yang haplotypes with more than 10% mutational variations. Indeed, the prevalence of each of the distinct yin and yang haplotypes, despite strong coexistence and recombination opportunities, indicates very low recombination events between yin and yang haplotypes. However, as shown in Fig. 6, previous analyses of this region provided by the HapMap Consortium (http://hapmap.ncbi.nlm.nih.gov/downloads/recombination/) reported moderate recombination within the region, including an estimated recombination rate of 9.2 cM/Mb at rs10133120 in the 5′ end of gephyrin. Taken together, these results strongly suggest that recombinants comprised of two yin haplotypes and/or recombinants comprised of two yang haplotypes are more prevalent than recombinants merging yin and yang haplotypes together. This observation suggests that yin and yang haplotypes may have been favorably selected over merged yin and yang recombinants.


Human gephyrin is encompassed within giant functional noncoding yin-yang sequences.

Climer S, Templeton AR, Zhang W - Nat Commun (2015)

Recombination ratesShown are the recombination rates provided by the HapMap Consortium for the yin-yang region. These rates were computed using the CEU, CHB, JPT, and YRI population data. All of these positions are within the yin-yang region and the recombination rate of 9.2 cM Mb−1 was estimated at rs10133120 in the 5′ end of gephyrin.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4380243&req=5

Figure 6: Recombination ratesShown are the recombination rates provided by the HapMap Consortium for the yin-yang region. These rates were computed using the CEU, CHB, JPT, and YRI population data. All of these positions are within the yin-yang region and the recombination rate of 9.2 cM Mb−1 was estimated at rs10133120 in the 5′ end of gephyrin.
Mentions: Third, the unusual recombination patterns in this region support selection favoring the yin and yang haplotypes. A close examination of Figs. 1, 2, and 3 suggests that recombinants comprised of both a yin and yang parental haplotype are generally rare, particularly within gephyrin and upstream from this gene. Such a recombinant would appear as a horizontal bar comprised of blocks that are two different colors in Fig. 1. As shown in Fig. 2, nine of the 340 CHB and JPT haplotypes have between 10% and 90% yin/yang compositions; six of these represent yin-yang recombinants and three represent intermediate yin or yang haplotypes with more than 10% mutational variations. Indeed, the prevalence of each of the distinct yin and yang haplotypes, despite strong coexistence and recombination opportunities, indicates very low recombination events between yin and yang haplotypes. However, as shown in Fig. 6, previous analyses of this region provided by the HapMap Consortium (http://hapmap.ncbi.nlm.nih.gov/downloads/recombination/) reported moderate recombination within the region, including an estimated recombination rate of 9.2 cM/Mb at rs10133120 in the 5′ end of gephyrin. Taken together, these results strongly suggest that recombinants comprised of two yin haplotypes and/or recombinants comprised of two yang haplotypes are more prevalent than recombinants merging yin and yang haplotypes together. This observation suggests that yin and yang haplotypes may have been favorably selected over merged yin and yang recombinants.

Bottom Line: Its specific function is intricately regulated and its aberrant activities have been observed for a number of human diseases.The gephyrin yin-yang pair consists of 284 divergent nucleotide states and both variants vary drastically from their mutual ancestral haplotype, suggesting rapid evolution.This discovery holds potential to deepen our understanding of variable human-specific regulation of gephyrin while providing clues for rapid evolutionary events and allelic migrations buried within human history.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Engineering, Washington University, St Louis, Missouri 63130, USA.

ABSTRACT
Gephyrin is a highly conserved gene that is vital for the organization of proteins at inhibitory receptors, molybdenum cofactor biosynthesis and other diverse functions. Its specific function is intricately regulated and its aberrant activities have been observed for a number of human diseases. Here we report a remarkable yin-yang haplotype pattern encompassing gephyrin. Yin-yang haplotypes arise when a stretch of DNA evolves to present two disparate forms that bear differing states for nucleotide variations along their lengths. The gephyrin yin-yang pair consists of 284 divergent nucleotide states and both variants vary drastically from their mutual ancestral haplotype, suggesting rapid evolution. Several independent lines of evidence indicate strong positive selection on the region and suggest these high-frequency haplotypes represent two distinct functional mechanisms. This discovery holds potential to deepen our understanding of variable human-specific regulation of gephyrin while providing clues for rapid evolutionary events and allelic migrations buried within human history.

No MeSH data available.


Related in: MedlinePlus