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Faster evolving Drosophila paralogs lose expression rate and ubiquity and accumulate more non-synonymous SNPs.

ABSTRACT: BACKGROUND: Duplicated genes can indefinately persist in genomes if either both copies retain the original function due to dosage benefit (gene conservation), or one of the copies assumes a novel function (neofunctionalization), or both copies become required to perform the function previously accomplished by a single copy (subfunctionalization), or through a combination of these mechanisms. Different models of duplication retention imply different predictions about substitution rates in the coding portion of paralogs and about asymmetry of these rates. RESULTS: We analyse sequence evolution asymmetry in paralogs present in 12 Drosophila genomes using the nearest non-duplicated orthologous outgroup as a reference. Those paralogs present in D. melanogaster are analysed in conjunction with the asymmetry of expression rate and ubiquity and of segregating non-synonymous polymorphisms in the same paralogs. Paralogs accumulate substitutions, on average, faster than their nearest singleton orthologs. The distribution of paralogs' substitution rate asymmetry is overdispersed relative to that of orthologous clades, containing disproportionally more unusually symmetric and unusually asymmetric clades. We show that paralogs are more asymmetric in: a) clades orthologous to highly constrained singleton genes; b) genes with high expression level; c) genes with ubiquitous expression and d) non-tandem duplications. We further demonstrate that, in each asymmetrically evolving pair of paralogs, the faster evolving member of the pair tends to have lower average expression rate, lower expression uniformity and higher frequency of non-synonymous SNPs than its slower evolving counterpart. CONCLUSIONS: Our findings are consistent with the hypothesis that many duplications in Drosophila are retained despite stabilising selection being more relaxed in one of the paralogs than in the other, suggesting a widespread unfinished pseudogenization. This phenomenon is likely to make detection of neo- and subfunctionalization signatures difficult, as these models of duplication retention also predict asymmetries in substitution rates and expression profiles.

SUBMITTER: Yampolsky LY

PROVIDER: S-EPMC3906896 | biostudies-other | 2014

REPOSITORIES: biostudies-other

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Faster evolving Drosophila paralogs lose expression rate and ubiquity and accumulate more non-synonymous SNPs.

Yampolsky Lev Y LY Bouzinier Michael A MA

Biology direct 20140117

<h4>Background</h4>Duplicated genes can indefinately persist in genomes if either both copies retain the original function due to dosage benefit (gene conservation), or one of the copies assumes a novel function (neofunctionalization), or both copies become required to perform the function previously accomplished by a single copy (subfunctionalization), or through a combination of these mechanisms. Different models of duplication retention imply different predictions about substitution rates in ...[more]

PMID: 24438455

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Project description:BackgroundTuftelin 1 (TUFT1) gene is important in the development and mineralization of dental enamel. The study aimed to identify potential functionally deleterious non-synonymous SNPs (nsSNPs) in the TUFT1 gene by using different in silico tools. The deleterious missense SNPs were identified from SIFT, PolyPhen-2, PROVEAN, SNPs & GO, PANTHER, and SNAP2. The stabilization, conservation, and three-dimensional modeling of mutant proteins were analyzed by I-Mutant 3.0, Consurf, and Project HOPE, respectively. The protein-protein interaction using STRING, GeneMANIA for gene-gene interaction, and DynaMut for evaluating the impact of the mutation on protein stability, conformation, and flexibility.ResultsEight deleterious nsSNPs (E242A, R303W, K182N, K123N, R117W, H289Q, R203W, and Q107R) out of 304 were found to have high-risk damaging effects using six in silico tools. Among them, K182N and K123N alone had increased stability, whereas E242A, R303W, R117W, H289Q, Q107R, and R203W exhibited a decrease in protein stability, based on DDG values. Meanwhile, all the eight deleterious nsSNPs altered the size, charge, hydrophobicity, and spatial organization of the amino acids and predominantly had alpha helix domains. These deleterious variants were located in highly conserved regions except R203W. Protein-protein interaction predicted that TUFT1 interacted with ten proteins that are involved in enamel mineralization and odontogenesis. Gene-gene interaction network showed that TUFT1 is involved in physical interactions, gene co-localization, and pathway interactions. DynaMut ΔΔG values predicted that five nsSNPs were destabilizing the protein, ΔΔG ENCoM values showed a destabilizing effect for all mutants, and seven nsSNPs increased the molecular flexibility of TUFT1.ConclusionOur study predicted eight functional SNPs that had detrimental effects on the structure and function of the TUFT1 gene. This will aid in the development of candidate deleterious markers as a potential target for disease diagnosis and therapeutic interventions.

Dataset Information

Faster evolving Drosophila paralogs lose expression rate and ubiquity and accumulate more non-synonymous SNPs.

Publications

Faster evolving Drosophila paralogs lose expression rate and ubiquity and accumulate more non-synonymous SNPs.

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