Identifying concerted evolution and gene conversion in mammalian gene pairs lasting over 100 million years

Andrew R Carson,Stephen W Scherer

doi:10.1186/1471-2148-9-156

Andrew R Carson, Stephen W Scherer

Open Access

https://doi.org/10.1186/1471-2148-9-156

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Abstract

BackgroundConcerted evolution occurs in multigene families and is characterized by stretches of homogeneity and higher sequence similarity between paralogues than between orthologues. Here we identify human gene pairs that have undergone concerted evolution, caused by ongoing gene conversion, since at least the human-mouse divergence. Our strategy involved the identification of duplicated genes with greater similarity within a species than between species. These genes were required to be present in multiple mammalian genomes, suggesting duplication early in mammalian divergence. To eliminate genes that have been conserved due to strong purifying selection, our analysis also required at least one intron to have retained high sequence similarity between paralogues.ResultsWe identified three human gene pairs undergoing concerted evolution (BMP8A/B, DDX19A/B, and TUBG1/2). Phylogenetic investigations reveal that in each case the duplication appears to have occurred prior to eutherian mammalian radiation, with exactly two paralogues present in all examined species. This indicates that all three gene duplication events were established over 100 million years ago.ConclusionThe extended duration of concerted evolution in multiple distant lineages suggests that there has been prolonged homogenization of specific segments within these gene pairs. Although we speculate that selection for homogenization could have been utilized in order to maintain crucial homo- or hetero- binding domains, it remains unclear why gene conversion has persisted for such extended periods of time. Through these analyses, our results demonstrate additional examples of a process that plays a definite, although unspecified, role in molecular evolution.

Highlights

Concerted evolution occurs in multigene families and is characterized by stretches of homogeneity and higher sequence similarity between paralogues than between orthologues
Due to the filtering steps we utilized, each gene pair is less than 1 Mb apart and shares high sequence similarity (>97%) in at least two consecutive exons and their intervening intron
Homogenization or increased GC by themselves do not prove gene conversion is acting within these regions, in combination with mosaic evolution (Figures 1 and 3) and a consistent copy number, this evidence supports gene conversion, rather than unequal crossing over, as the cause of the concerted evolution in these gene pairs

Summary

Introduction

Concerted evolution occurs in multigene families and is characterized by stretches of homogeneity and higher sequence similarity between paralogues than between orthologues. Our strategy involved the identification of duplicated genes with greater similarity within a species than between species These genes were required to be present in multiple mammalian genomes, suggesting duplication early in mammalian divergence. Duplicated genes are subject to the same forces that affect the evolution of single copy genes These include genetic drift, which is opposed by negative or purifying selection, and positive selection, which can fix advantageous changes faster than expected by chance [2,3,4]. Functional redundancy can permit the accumulation of changes in one copy of the gene without negative consequences to an organism's proteome. Subfunctionalization [6,7], where an ancestral gene's functions are shared between the descendant genes, and neofunctionalization [5], where one copy acquires a novel gene function, are possible consequences of divergence following gene duplication

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