Region-specific expression of young small-scale duplications in the human central nervous system

Solène Brohard-Julien,Vincent Meyer,Jean-François Deleuze,Edith Le Floch,Smahane Chalabi,Christophe Battail,Vincent Frouin

doi:10.1186/s12862-021-01794-w

Abstract

BackgroundThe duplication of genes is one of the main genetic mechanisms that led to the gain in complexity of biological tissue. Although the implication of duplicated gene expression in brain evolution was extensively studied through comparisons between organs, their role in the regional specialization of the adult human central nervous system has not yet been well described.ResultsOur work explored intra-organ expression properties of paralogs through multiple territories of the human central nervous system (CNS) using transcriptome data generated by the Genotype-Tissue Expression (GTEx) consortium. Interestingly, we found that paralogs were associated with region-specific expression in CNS, suggesting their involvement in the differentiation of these territories. Beside the influence of gene expression level on region-specificity, we observed the contribution of both duplication age and duplication type to the CNS region-specificity of paralogs. Indeed, we found that small scale duplicated genes (SSDs) and in particular ySSDs (SSDs younger than the 2 rounds of whole genome duplications) were more CNS region-specific than other paralogs. Next, by studying the two paralogs of ySSD pairs, we observed that when they were region-specific, they tend to be specific to the same region more often than for other paralogs, showing the high co-expression of ySSD pairs. The extension of this analysis to families of paralogs showed that the families with co-expressed gene members (i.e. homogeneous families) were enriched in ySSDs. Furthermore, these homogeneous families tended to be region-specific families, where the majority of their gene members were specifically expressed in the same region.ConclusionsOverall, our study suggests the involvement of ySSDs in the differentiation of human central nervous system territories. Therefore, we show the relevance of exploring region-specific expression of paralogs at the intra-organ level.

Highlights

The duplication of genes is one of the main genetic mechanisms that led to the gain in complexity of biological tissue
The fact that some paralogs are retained in genomes through evolution seems to be initially favored by dosage balance [3] and their long-term preservation is made possible by the following two Brohard‐Julien et al BMC Ecol Evo (2021) 21:59 processes: the neo-functionalization, which consists in the gain of a new function by one duplicate potentially associated with a different spatial expression [4,5,6,7], or the sub-functionalization which consists in the partition of the ancestral function or spatial expression between duplicates [8, 9]
Among the 60% of human genes considered as paralogs [2], some come from whole-genome duplications (WGD) in early vertebrate lineage approximately 500 million years ago [12, 13], the others come from small scale duplications (SSD) that have occurred throughout the evolution [14]

Summary

Introduction

The duplication of genes is one of the main genetic mechanisms that led to the gain in complexity of biological tissue. The implication of duplicated gene expression in brain evolution was extensively studied through comparisons between organs, their role in the regional specialization of the adult human central nervous system has not yet been well described. A comparison in mammals, notably in humans, of the brain transcriptome with those of other organs has shown that WGDs tend to be enriched in brain-specific genes compared to SSDs [15, 16]. This supports the theory that genome duplications have allowed vertebrates to develop more complex cellular organizations of the central nervous system (CNS) [17, 18]

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