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Albuminoid genes: evolving at the interface of dispensability and selection.

Mozzi A, Forni D, Cagliani R, Pozzoli U, Vertemara J, Bresolin N, Sironi M - Genome Biol Evol (2014)

Bottom Line: Population genetic analysis revealed that GC was also the target of locally exerted selective pressure, which drove the frequency increase of different haplotypes in distinct human populations.A search for known variants that modulate GC and 25-hydroxyvitamin D concentrations revealed linkage disequilibrium with positively selected variants, although European and Asian major GC haplotypes carry alleles with reported opposite effect on GC concentration.Data herein indicate that albumin, an extremely abundant housekeeping protein, was the target of pervasive and episodic selection in mammals, whereas GC represented a selection target during the recent evolution of human populations.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy manuela.sironi@bp.lnf.it.

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Natural selection at GC in human populations. (A) Schematic representation of GC within the UCSC Genome Browser view. The location of the selection targets and of the GWAS variant are also shown, together with relevant ENCODE tracks. Variants are color coded by population: YRI, green; CEU, blue; CHBJPT, red. A sliding-window analysis of normalized DH is also shown for YRI; the horizontal line represents the fifth percentile in the distribution of DH values. (B) Schematic representation of CEU (left) and CHBJPT (right) haplotypes for genomic regions centered around the selected variants. Each line represents a haplotype, columns indicate polymorphic positions. Dark gray, derived alleles; light gray, ancestral alleles. The thick horizontal line separates haplotypes carrying the ancestral (bottom) and derived (top) allele. (C) LD plot (r2) for the selected targets in the three populations, the GWAS variant, and two nonsynonymous SNPs in GC (see text). Variants are color coded as in (A). (D) Schematic representation of the major human haplotypes for rs2283679, rs2298850, rs4588, and rs7041. Arrows indicate the association with increased or decreased levels of vitamin D-binding protein (GC) and 25-hydroxyvitamin D (25ODH). The selected allele in CHBJPT for rs2298850 is colored in red. The frequency for each haplotype in the three populations is also reported.
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evu235-F4: Natural selection at GC in human populations. (A) Schematic representation of GC within the UCSC Genome Browser view. The location of the selection targets and of the GWAS variant are also shown, together with relevant ENCODE tracks. Variants are color coded by population: YRI, green; CEU, blue; CHBJPT, red. A sliding-window analysis of normalized DH is also shown for YRI; the horizontal line represents the fifth percentile in the distribution of DH values. (B) Schematic representation of CEU (left) and CHBJPT (right) haplotypes for genomic regions centered around the selected variants. Each line represents a haplotype, columns indicate polymorphic positions. Dark gray, derived alleles; light gray, ancestral alleles. The thick horizontal line separates haplotypes carrying the ancestral (bottom) and derived (top) allele. (C) LD plot (r2) for the selected targets in the three populations, the GWAS variant, and two nonsynonymous SNPs in GC (see text). Variants are color coded as in (A). (D) Schematic representation of the major human haplotypes for rs2283679, rs2298850, rs4588, and rs7041. Arrows indicate the association with increased or decreased levels of vitamin D-binding protein (GC) and 25-hydroxyvitamin D (25ODH). The selected allele in CHBJPT for rs2298850 is colored in red. The frequency for each haplotype in the three populations is also reported.

Mentions: In YRI one variant (rs17766549) at high DAF (0.98) was an FST outlier in the YRI/CEU comparison, and also displayed an unusually high DIND value (table 4). These results were confirmed by the DH analysis (fig. 4A): The variant fell in a local valley of DH, in line with this statistic having maximum power for high-frequency sweeps (Zeng et al. 2006) (table 4). Overall, these results indicate that a selective sweep drove the frequency increase of this variant in YRI. The SNP is located in a region where enhancer- and promoter-associated histone marks are located, as assessed by ENCODE data (fig. 4A).Fig. 4.—


Albuminoid genes: evolving at the interface of dispensability and selection.

Mozzi A, Forni D, Cagliani R, Pozzoli U, Vertemara J, Bresolin N, Sironi M - Genome Biol Evol (2014)

Natural selection at GC in human populations. (A) Schematic representation of GC within the UCSC Genome Browser view. The location of the selection targets and of the GWAS variant are also shown, together with relevant ENCODE tracks. Variants are color coded by population: YRI, green; CEU, blue; CHBJPT, red. A sliding-window analysis of normalized DH is also shown for YRI; the horizontal line represents the fifth percentile in the distribution of DH values. (B) Schematic representation of CEU (left) and CHBJPT (right) haplotypes for genomic regions centered around the selected variants. Each line represents a haplotype, columns indicate polymorphic positions. Dark gray, derived alleles; light gray, ancestral alleles. The thick horizontal line separates haplotypes carrying the ancestral (bottom) and derived (top) allele. (C) LD plot (r2) for the selected targets in the three populations, the GWAS variant, and two nonsynonymous SNPs in GC (see text). Variants are color coded as in (A). (D) Schematic representation of the major human haplotypes for rs2283679, rs2298850, rs4588, and rs7041. Arrows indicate the association with increased or decreased levels of vitamin D-binding protein (GC) and 25-hydroxyvitamin D (25ODH). The selected allele in CHBJPT for rs2298850 is colored in red. The frequency for each haplotype in the three populations is also reported.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255767&req=5

evu235-F4: Natural selection at GC in human populations. (A) Schematic representation of GC within the UCSC Genome Browser view. The location of the selection targets and of the GWAS variant are also shown, together with relevant ENCODE tracks. Variants are color coded by population: YRI, green; CEU, blue; CHBJPT, red. A sliding-window analysis of normalized DH is also shown for YRI; the horizontal line represents the fifth percentile in the distribution of DH values. (B) Schematic representation of CEU (left) and CHBJPT (right) haplotypes for genomic regions centered around the selected variants. Each line represents a haplotype, columns indicate polymorphic positions. Dark gray, derived alleles; light gray, ancestral alleles. The thick horizontal line separates haplotypes carrying the ancestral (bottom) and derived (top) allele. (C) LD plot (r2) for the selected targets in the three populations, the GWAS variant, and two nonsynonymous SNPs in GC (see text). Variants are color coded as in (A). (D) Schematic representation of the major human haplotypes for rs2283679, rs2298850, rs4588, and rs7041. Arrows indicate the association with increased or decreased levels of vitamin D-binding protein (GC) and 25-hydroxyvitamin D (25ODH). The selected allele in CHBJPT for rs2298850 is colored in red. The frequency for each haplotype in the three populations is also reported.
Mentions: In YRI one variant (rs17766549) at high DAF (0.98) was an FST outlier in the YRI/CEU comparison, and also displayed an unusually high DIND value (table 4). These results were confirmed by the DH analysis (fig. 4A): The variant fell in a local valley of DH, in line with this statistic having maximum power for high-frequency sweeps (Zeng et al. 2006) (table 4). Overall, these results indicate that a selective sweep drove the frequency increase of this variant in YRI. The SNP is located in a region where enhancer- and promoter-associated histone marks are located, as assessed by ENCODE data (fig. 4A).Fig. 4.—

Bottom Line: Population genetic analysis revealed that GC was also the target of locally exerted selective pressure, which drove the frequency increase of different haplotypes in distinct human populations.A search for known variants that modulate GC and 25-hydroxyvitamin D concentrations revealed linkage disequilibrium with positively selected variants, although European and Asian major GC haplotypes carry alleles with reported opposite effect on GC concentration.Data herein indicate that albumin, an extremely abundant housekeeping protein, was the target of pervasive and episodic selection in mammals, whereas GC represented a selection target during the recent evolution of human populations.

View Article: PubMed Central - PubMed

Affiliation: Bioinformatics, Scientific Institute IRCCS E.MEDEA, Bosisio Parini, Italy manuela.sironi@bp.lnf.it.

Show MeSH