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Sequence diversity and conservation in factors influencing succinate dehydrogenase flavinylation.

ABSTRACT: The mitochondrial enzyme succinate dehydrogenase (SDH) consists of four subunits, a flavoprotein (SDH1), an iron-sulfur (Fe-S) protein (SDH2) and two integral membrane subunits (SDH3/SDH4). In mammals and yeast, an assembly factor termed SDHAF2/SDH5 is required for accumulation of flavinylated SDH1. In Arabidopsis, we have recently reported the characterization of an unknown function protein with low sequence similarity to SDHAF2 that is needed for assembly and activity of SDH and also for normal root elongation. (1) In this short communication, we have reviewed the sequence diversity and conservation of SDHAF2 across kingdoms based on phylogenetic analysis. Given that flavinylation of SDH is dependent on the SDH1:SDHAF2 interaction, we have also discussed the conservation of the C-terminal tail of SDH1, which is required for this interaction process. In combination, we provide comparative evidence for a conserved role of SDHAF2 as an assembly factor from animals to plants.

SUBMITTER: Huang S

PROVIDER: S-EPMC3656984 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Sequence diversity and conservation in factors influencing succinate dehydrogenase flavinylation.

Huang Shaobai S Millar A Harvey AH

Plant signaling & behavior 20121115 2

The mitochondrial enzyme succinate dehydrogenase (SDH) consists of four subunits, a flavoprotein (SDH1), an iron-sulfur (Fe-S) protein (SDH2) and two integral membrane subunits (SDH3/SDH4). In mammals and yeast, an assembly factor termed SDHAF2/SDH5 is required for accumulation of flavinylated SDH1. In Arabidopsis, we have recently reported the characterization of an unknown function protein with low sequence similarity to SDHAF2 that is needed for assembly and activity of SDH and also for norma ...[more]

PMID: 23154507

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Project description:BackgroundBalancing selection operating for long evolutionary periods at a locus is characterized by the maintenance of distinct alleles because of a heterozygote or rare-allele advantage. The loci under balancing selection are distinguished by their unusually high polymorphism levels. In this report, we provide statistical and comparative genetic evidence suggesting that the SDHA gene is under long-term balancing selection. SDHA encodes the major catalytical subunit (flavoprotein, Fp) of the succinate dehydrogenase enzyme complex (SDH; mitochondrial complex II). The inhibition of Fp by homozygous SDHA mutations or by 3-nitropropionic acid poisoning causes central nervous system pathologies. In contrast, heterozygous mutations in SDHB, SDHC, and SDHD, the other SDH subunit genes, cause hereditary paraganglioma (PGL) tumors, which show constitutive activation of pathways induced by oxygen deprivation (hypoxia).ResultsWe sequenced the four SDH subunit genes (10.8 kb) in 24 African American and 24 European American samples. We also sequenced the SDHA gene (2.8 kb) in 18 chimpanzees. Increased nucleotide diversity distinguished the human SDHA gene from its chimpanzee ortholog and from the PGL genes. Sequence analysis uncovered two common SDHA missense variants and refuted the previous suggestions that these variants originate from different genetic loci. Two highly dissimilar SDHA haplotype clusters were present in intermediate frequencies in both racial groups. The SDHA variation pattern showed statistically significant deviations from neutrality by the Tajima, Fu and Li, Hudson-Kreitman-Aguadé, and Depaulis haplotype number tests. Empirically, the elevated values of the nucleotide diversity (% pi = 0.231) and the Tajima statistics (D = 1.954) in the SDHA gene were comparable with the most outstanding cases for balancing selection in the African American population.ConclusionThe SDHA gene has a strong signature of balancing selection. The SDHA variants that have increased in frequency during human evolution might, by influencing the regulation of cellular oxygen homeostasis, confer protection against certain environmental toxins or pathogens that are prevalent in Africa.

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Sequence diversity and conservation in factors influencing succinate dehydrogenase flavinylation.

Publications

Sequence diversity and conservation in factors influencing succinate dehydrogenase flavinylation.

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