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

Michael A Bouzinier,Lev Y Yampolsky

doi:10.1186/1745-6150-9-2

Michael A Bouzinier, Lev Y Yampolsky

Open Access

https://doi.org/10.1186/1745-6150-9-2

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Abstract

BackgroundDuplicated 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.ResultsWe 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.ConclusionsOur 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.ReviewersThis article has been reviewed by Dr. Jia Zeng (nominated by Dr. I. King Jordan), Dr. Fyodor Kondrashov and Dr. Yuri Wolf.

Highlights

IntroductionDuplicated 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
Duplicated genes can indefinately persist in genomes if either both copies retain the original function due to dosage benefit, or one of the copies assumes a novel function, or both copies become required to perform the function previously accomplished by a single copy, or through a combination of these mechanisms
During pseudogenization and neofunctionalization selective constraints are relaxed in one copy but not the other; such pairs of paralogs may be expected to evolve in an unusually asymmetric manner relative to the null expectation of equal rates in both paralogous clades: one paralog accumulates more mutations than the other and that difference is too large to be explained by binomial process of incurring random mutations

Summary

Introduction

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. This may happen either by fixation of hypomorphic alleles in both copies or due to differential loss of regulatory elements [3,7,11,12] Each of these duplication retention models implies different predictions about relaxation of stabilising selection in neither, one, or both paralogs [6,7]. Paralogs retained by gene conservation or balanced degradation type of subfunctionalization may be hypothesised to accumulate changes in an unusually symmetric manner, i.e. with rates more similar than one might expect from the random null expectation, something that can be much harder to detect and test. Such symmetry may be further explained by the action of gene conversion or unequal crossing over homogenizing paralogous copies [13]

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