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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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Analysis of positively selected sites in ALB. (A) Ribbon representation of human albumin structure (PDB code: 1HK4); color codes denote distinct domains: I (magenta), II (green), and III (blue); dark and light color shades indicate the A and B subdomain organization. Albumin-bound fatty acid (black) and thyroxine molecules (gray) are represented as sticks. The fifth additional fatty acids-induced thyroxine-binding site is circled. Binding sites for heme, bilirubin, prostaglandins, and drugs are mapped onto the structure. (B) Positively selected sites mapped onto the albumin structure. Color codes are as follows: Red, positively selected sites in the whole phylogeny; yellow, lineage-specific sites; orange, positively selected sites in the chimpanzee lineage; cyan, positively selected sites in the human lineage. Bound fatty acid (black) and thyroxine molecules (gray) are also shown. (C) Representation of the albumin/FcRn complex (PDB code: 4K71). Albumin is shown in gray, the MHC class I-α chain in green and β2-microglobulin in blue. Positively selected sites located at the contact interface are indicated.
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evu235-F2: Analysis of positively selected sites in ALB. (A) Ribbon representation of human albumin structure (PDB code: 1HK4); color codes denote distinct domains: I (magenta), II (green), and III (blue); dark and light color shades indicate the A and B subdomain organization. Albumin-bound fatty acid (black) and thyroxine molecules (gray) are represented as sticks. The fifth additional fatty acids-induced thyroxine-binding site is circled. Binding sites for heme, bilirubin, prostaglandins, and drugs are mapped onto the structure. (B) Positively selected sites mapped onto the albumin structure. Color codes are as follows: Red, positively selected sites in the whole phylogeny; yellow, lineage-specific sites; orange, positively selected sites in the chimpanzee lineage; cyan, positively selected sites in the human lineage. Bound fatty acid (black) and thyroxine molecules (gray) are also shown. (C) Representation of the albumin/FcRn complex (PDB code: 4K71). Albumin is shown in gray, the MHC class I-α chain in green and β2-microglobulin in blue. Positively selected sites located at the contact interface are indicated.

Mentions: Albumin presents a modular structural organization composed of three homologous helical domains (I, II, and III) arranged in a heart-shaped molecule. Each domain comprises two separated subdomains (A and B), containing six and four helices, respectively. Available crystallographic data revealed binding sites for fatty acids (Bhattacharya et al. 2000), hemin, bilirubin (Zunszain et al. 2003, 2008), thyroxine hormone (Petitpas et al. 2003), prostaglandins (Yamaguchi et al. 2010), and a wide variety of chemical drugs (Curry 2009) (fig. 2A).Fig. 2.—


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)

Analysis of positively selected sites in ALB. (A) Ribbon representation of human albumin structure (PDB code: 1HK4); color codes denote distinct domains: I (magenta), II (green), and III (blue); dark and light color shades indicate the A and B subdomain organization. Albumin-bound fatty acid (black) and thyroxine molecules (gray) are represented as sticks. The fifth additional fatty acids-induced thyroxine-binding site is circled. Binding sites for heme, bilirubin, prostaglandins, and drugs are mapped onto the structure. (B) Positively selected sites mapped onto the albumin structure. Color codes are as follows: Red, positively selected sites in the whole phylogeny; yellow, lineage-specific sites; orange, positively selected sites in the chimpanzee lineage; cyan, positively selected sites in the human lineage. Bound fatty acid (black) and thyroxine molecules (gray) are also shown. (C) Representation of the albumin/FcRn complex (PDB code: 4K71). Albumin is shown in gray, the MHC class I-α chain in green and β2-microglobulin in blue. Positively selected sites located at the contact interface are indicated.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

evu235-F2: Analysis of positively selected sites in ALB. (A) Ribbon representation of human albumin structure (PDB code: 1HK4); color codes denote distinct domains: I (magenta), II (green), and III (blue); dark and light color shades indicate the A and B subdomain organization. Albumin-bound fatty acid (black) and thyroxine molecules (gray) are represented as sticks. The fifth additional fatty acids-induced thyroxine-binding site is circled. Binding sites for heme, bilirubin, prostaglandins, and drugs are mapped onto the structure. (B) Positively selected sites mapped onto the albumin structure. Color codes are as follows: Red, positively selected sites in the whole phylogeny; yellow, lineage-specific sites; orange, positively selected sites in the chimpanzee lineage; cyan, positively selected sites in the human lineage. Bound fatty acid (black) and thyroxine molecules (gray) are also shown. (C) Representation of the albumin/FcRn complex (PDB code: 4K71). Albumin is shown in gray, the MHC class I-α chain in green and β2-microglobulin in blue. Positively selected sites located at the contact interface are indicated.
Mentions: Albumin presents a modular structural organization composed of three homologous helical domains (I, II, and III) arranged in a heart-shaped molecule. Each domain comprises two separated subdomains (A and B), containing six and four helices, respectively. Available crystallographic data revealed binding sites for fatty acids (Bhattacharya et al. 2000), hemin, bilirubin (Zunszain et al. 2003, 2008), thyroxine hormone (Petitpas et al. 2003), prostaglandins (Yamaguchi et al. 2010), and a wide variety of chemical drugs (Curry 2009) (fig. 2A).Fig. 2.—

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