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Intraspecific polymorphism, interspecific divergence, and the origins of function-altering mutations in deer mouse hemoglobin.

Natarajan C, Hoffmann FG, Lanier HC, Wolf CJ, Cheviron ZA, Spangler ML, Weber RE, Fago A, Storz JF - Mol. Biol. Evol. (2015)

Bottom Line: Variation in Hb-O2 affinity within and among populations of P. maniculatus is attributable to numerous amino acid mutations that have individually small effects.Partly as a result of concerted evolution between tandemly duplicated globin genes, the same amino acid changes that contribute to variation in Hb function within P. maniculatus also contribute to divergence in Hb function among different species of Peromyscus.In the case of function-altering Hb mutations in Peromyscus, there is no qualitative or quantitative distinction between segregating variants within species and fixed differences between species.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, University of Nebraska, Lincoln.

No MeSH data available.


Intraspecific polymorphism and interspecific divergence in the HBA and HBB genes of Peromyscus. (A) Alignment of 30 variable amino acid sites in 12 Peromyscus species. Shaded columns denote sites that harbor intermediate-frequency polymorphisms (MAF >0.05) in Peromyscus maniculatus. At each site, sizes of the letter codes for alternative amino acids are proportional to their representation in the sample, and therefore provide a graphical depiction of site-specific allele frequency variation within P. maniculatus (top) and conservation among species (bottom). The HBA-T1 and HBA-T2 paralogs are individually identified in P. maniculatus and P. keeni. For P. maniculatus, the “LA” and “HA” alleles refer to the predominant amino acid haplotypes sampled from lowland (Great Plains) and highland (Rocky Mountain) localities, respectively. Some species (P. leucopus, P. gossypinus, and P. melanophrys) possess a single-copy HBA gene. In the remaining species, “HBA-a” and “HBA-b” refer to paralogous sequences with unknown linkage order in the α-globin gene cluster. (B) Alignment of 30 variable amino acid sites in the HBB-T1 and HBB-T2 genes of 16 Peromyscus species. As in panel A, shaded columns denote sites that harbor intermediate-frequency polymorphisms in P. maniculatus. Sequence logos depict site-specific allele frequency variation within P. maniculatus (top) and conservation among species (bottom). In both panels, the tree topologies are based on a consensus of recent phylogenetic studies (Bradley et al. 2007; Gering et al. 2009).
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msu403-F3: Intraspecific polymorphism and interspecific divergence in the HBA and HBB genes of Peromyscus. (A) Alignment of 30 variable amino acid sites in 12 Peromyscus species. Shaded columns denote sites that harbor intermediate-frequency polymorphisms (MAF >0.05) in Peromyscus maniculatus. At each site, sizes of the letter codes for alternative amino acids are proportional to their representation in the sample, and therefore provide a graphical depiction of site-specific allele frequency variation within P. maniculatus (top) and conservation among species (bottom). The HBA-T1 and HBA-T2 paralogs are individually identified in P. maniculatus and P. keeni. For P. maniculatus, the “LA” and “HA” alleles refer to the predominant amino acid haplotypes sampled from lowland (Great Plains) and highland (Rocky Mountain) localities, respectively. Some species (P. leucopus, P. gossypinus, and P. melanophrys) possess a single-copy HBA gene. In the remaining species, “HBA-a” and “HBA-b” refer to paralogous sequences with unknown linkage order in the α-globin gene cluster. (B) Alignment of 30 variable amino acid sites in the HBB-T1 and HBB-T2 genes of 16 Peromyscus species. As in panel A, shaded columns denote sites that harbor intermediate-frequency polymorphisms in P. maniculatus. Sequence logos depict site-specific allele frequency variation within P. maniculatus (top) and conservation among species (bottom). In both panels, the tree topologies are based on a consensus of recent phylogenetic studies (Bradley et al. 2007; Gering et al. 2009).

Mentions: The survey of nucleotide polymorphism in the HBA genes of P. maniculatus from the central and western United States (n = 406 alleles) revealed 15 intermediate-frequency amino acid polymorphisms with minor allele frequencies (MAFs) greater than 0.05 (fig. 3A). We separately cloned and sequenced the tandemly linked HBA-T1 and HBA-T2 genes in a subset of specimens to obtain complete tetraploid genotypes ( = 228 experimentally phased alleles). Likewise, we generated tetraploid HBA-T1/HBA-T2 genotypes for P. keeni and diploid genotypes for the single-copy HBA-T1 gene of P. leucopus ( = 24 and 22 experimentally phased alleles, respectively). For each of these same three species we also generated polymorphism data for the downstream pseudogene (HBA-T3 in P. maniculatus and P. keeni, HBA-T2 in P. leucopus). Data for the HBA-T1 and HBA-T2 genes of P. maniculatus confirmed previous reports that the same alleles are segregating at both genes due to a history of interparalog gene conversion (Storz and Kelly 2008; Storz, Runck, et al. 2010). However, P. maniculatus specimens from one particular locality, Humboldt Co., CA, possess structurally distinct HBA paralogs that are distinguished by fixed or nearly fixed differences at six amino acid sites (supplementary fig. S3, Supplementary Material online). Amino acid replacements at most of the sites that distinguish HBA-T1 and HBA-T2 in the Humboldt mice are identical to sequence differences between alternative alleles that are segregating at both paralogs in mice from other regions (supplementary fig. S3, Supplementary Material online). HBA-T1 and HBA-T2 paralogs in the Humboldt mice are also characterized by far fewer shared polymorphisms in comparison with other population samples of P. maniculatus (supplementary table S2, Supplementary Material online), suggesting a lower rate of HBA-T1↔HBA-T2 gene conversion (and, hence, a lower rate of concerted evolution). However, overall sequence divergence between the HBA-T1 and HBA-T2 paralogs in the Humboldt mice was not unusually high compared with levels of interparalog divergence in other populations of P. maniculatus (supplementary table S2, Supplementary Material online).Fig. 3.


Intraspecific polymorphism, interspecific divergence, and the origins of function-altering mutations in deer mouse hemoglobin.

Natarajan C, Hoffmann FG, Lanier HC, Wolf CJ, Cheviron ZA, Spangler ML, Weber RE, Fago A, Storz JF - Mol. Biol. Evol. (2015)

Intraspecific polymorphism and interspecific divergence in the HBA and HBB genes of Peromyscus. (A) Alignment of 30 variable amino acid sites in 12 Peromyscus species. Shaded columns denote sites that harbor intermediate-frequency polymorphisms (MAF >0.05) in Peromyscus maniculatus. At each site, sizes of the letter codes for alternative amino acids are proportional to their representation in the sample, and therefore provide a graphical depiction of site-specific allele frequency variation within P. maniculatus (top) and conservation among species (bottom). The HBA-T1 and HBA-T2 paralogs are individually identified in P. maniculatus and P. keeni. For P. maniculatus, the “LA” and “HA” alleles refer to the predominant amino acid haplotypes sampled from lowland (Great Plains) and highland (Rocky Mountain) localities, respectively. Some species (P. leucopus, P. gossypinus, and P. melanophrys) possess a single-copy HBA gene. In the remaining species, “HBA-a” and “HBA-b” refer to paralogous sequences with unknown linkage order in the α-globin gene cluster. (B) Alignment of 30 variable amino acid sites in the HBB-T1 and HBB-T2 genes of 16 Peromyscus species. As in panel A, shaded columns denote sites that harbor intermediate-frequency polymorphisms in P. maniculatus. Sequence logos depict site-specific allele frequency variation within P. maniculatus (top) and conservation among species (bottom). In both panels, the tree topologies are based on a consensus of recent phylogenetic studies (Bradley et al. 2007; Gering et al. 2009).
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Related In: Results  -  Collection

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msu403-F3: Intraspecific polymorphism and interspecific divergence in the HBA and HBB genes of Peromyscus. (A) Alignment of 30 variable amino acid sites in 12 Peromyscus species. Shaded columns denote sites that harbor intermediate-frequency polymorphisms (MAF >0.05) in Peromyscus maniculatus. At each site, sizes of the letter codes for alternative amino acids are proportional to their representation in the sample, and therefore provide a graphical depiction of site-specific allele frequency variation within P. maniculatus (top) and conservation among species (bottom). The HBA-T1 and HBA-T2 paralogs are individually identified in P. maniculatus and P. keeni. For P. maniculatus, the “LA” and “HA” alleles refer to the predominant amino acid haplotypes sampled from lowland (Great Plains) and highland (Rocky Mountain) localities, respectively. Some species (P. leucopus, P. gossypinus, and P. melanophrys) possess a single-copy HBA gene. In the remaining species, “HBA-a” and “HBA-b” refer to paralogous sequences with unknown linkage order in the α-globin gene cluster. (B) Alignment of 30 variable amino acid sites in the HBB-T1 and HBB-T2 genes of 16 Peromyscus species. As in panel A, shaded columns denote sites that harbor intermediate-frequency polymorphisms in P. maniculatus. Sequence logos depict site-specific allele frequency variation within P. maniculatus (top) and conservation among species (bottom). In both panels, the tree topologies are based on a consensus of recent phylogenetic studies (Bradley et al. 2007; Gering et al. 2009).
Mentions: The survey of nucleotide polymorphism in the HBA genes of P. maniculatus from the central and western United States (n = 406 alleles) revealed 15 intermediate-frequency amino acid polymorphisms with minor allele frequencies (MAFs) greater than 0.05 (fig. 3A). We separately cloned and sequenced the tandemly linked HBA-T1 and HBA-T2 genes in a subset of specimens to obtain complete tetraploid genotypes ( = 228 experimentally phased alleles). Likewise, we generated tetraploid HBA-T1/HBA-T2 genotypes for P. keeni and diploid genotypes for the single-copy HBA-T1 gene of P. leucopus ( = 24 and 22 experimentally phased alleles, respectively). For each of these same three species we also generated polymorphism data for the downstream pseudogene (HBA-T3 in P. maniculatus and P. keeni, HBA-T2 in P. leucopus). Data for the HBA-T1 and HBA-T2 genes of P. maniculatus confirmed previous reports that the same alleles are segregating at both genes due to a history of interparalog gene conversion (Storz and Kelly 2008; Storz, Runck, et al. 2010). However, P. maniculatus specimens from one particular locality, Humboldt Co., CA, possess structurally distinct HBA paralogs that are distinguished by fixed or nearly fixed differences at six amino acid sites (supplementary fig. S3, Supplementary Material online). Amino acid replacements at most of the sites that distinguish HBA-T1 and HBA-T2 in the Humboldt mice are identical to sequence differences between alternative alleles that are segregating at both paralogs in mice from other regions (supplementary fig. S3, Supplementary Material online). HBA-T1 and HBA-T2 paralogs in the Humboldt mice are also characterized by far fewer shared polymorphisms in comparison with other population samples of P. maniculatus (supplementary table S2, Supplementary Material online), suggesting a lower rate of HBA-T1↔HBA-T2 gene conversion (and, hence, a lower rate of concerted evolution). However, overall sequence divergence between the HBA-T1 and HBA-T2 paralogs in the Humboldt mice was not unusually high compared with levels of interparalog divergence in other populations of P. maniculatus (supplementary table S2, Supplementary Material online).Fig. 3.

Bottom Line: Variation in Hb-O2 affinity within and among populations of P. maniculatus is attributable to numerous amino acid mutations that have individually small effects.Partly as a result of concerted evolution between tandemly duplicated globin genes, the same amino acid changes that contribute to variation in Hb function within P. maniculatus also contribute to divergence in Hb function among different species of Peromyscus.In the case of function-altering Hb mutations in Peromyscus, there is no qualitative or quantitative distinction between segregating variants within species and fixed differences between species.

View Article: PubMed Central - PubMed

Affiliation: School of Biological Sciences, University of Nebraska, Lincoln.

No MeSH data available.