Divergence of Spatial Gene Expression Profiles Following Species-Specific Gene Duplications in Human and Mouse

Abstract

To examine the process by which duplicated genes diverge in function, we studied how the gene expression profiles of orthologous gene sets in human and mouse are affected by the presence of additional recent species-specific paralogs. Gene expression profiles were compared across 16 homologous tissues in human and mouse using microarray data from the Gene Expression Atlas for 1575 sets of orthologs including 250 with species-specific paralogs. We find that orthologs that have undergone recent duplication are less likely to have strongly correlated expression profiles than those that remain in a one-to-one relationship between human and mouse. There is a general trend for paralogous genes to become more specialized in their expression patterns, with decreased breadth and increased specificity of expression as gene family size increases. Despite this trend, detailed examination of some particular gene families where species-specific duplications have occurred indicated several examples of apparent neofunctionalization of duplicated genes, but only one case of subfunctionalization. Often, the expression of both copies of a duplicated gene appears to have changed relative to the ancestral state. Our results suggest that gene expression profiles are surprisingly labile and that expression in a particular tissue may be gained or lost repeatedly during the evolution of even small gene families. We conclude that gene duplication is a major driving force behind the emergence of divergent gene expression patterns

Paralogs in Polyploids: One for All and All for One?

“…According to Blanc and Wolfe (2004) more than 50% of the paralogous pairs in A. thaliana display significantly different patterns of expression. Similar results have been obtained for gene duplicates in mouse and human (Huminiecki and Wolfe, 2004), suggesting that this might be a more general phenomenon. Moreover, in the context of A. thaliana, genes whose expression profiles were significantly correlated, which are likely to interact, diverged from the corresponding paralogs in the same direction (Blanc and Wolfe, 2004).…”

Primate genome architecture influences structural variation mechanisms and functional consequences

“…Indeed, different possible fates of gene duplications have been proposed, which are referred to as neofunctionalization (i.e., a gene duplicate or paralog acquires a unique function) and subfunctionalization [specialization of both copies (parent and duplicate), each of which retain different subfunctions of the ancestral gene] (45). Roles of neofunctionalization and subfunctionalization have previously been studied in different organisms (45,46), including humans, in which ancient gene duplications occurring after the humanmouse split (>90 Mya) were evaluated for tissue expression (47). Our duplication map enabled us to associate gene duplication across recent primate evolution and revealed 13 recently duplicated genes that are candidates for neofunctionalization (i.e., gene duplication coinciding with newly acquired tissue expression.)…”

Deeply conserved chordate noncoding sequences preserve genome synteny but do not drive gene duplicate retention

“…This model, called the duplication-degeneration-complementation (DDC) model, can act upon any gene with multiple essential subfunctions that can be separated by mutation, and while there is some evidence that this can occur at the protein-coding level for genes with domains of distinct function (e.g., Cusack and Wolfe 2007), the majority of reports supporting this model have focused on cis-regulation. Clearly, expression partitioning does occur frequently in retained gene duplicates (Huminiecki and Wolfe 2004;Postlethwait et al 2004;Li et al 2005;Duarte et al 2006;Woolfe and Elgar 2007), and in yeast, genes with complex cis-regulation are over-retained after duplication (He and Zhang 2005). Within metazoan lineages, the same types of gene functions that are enriched near CNEs are also over-retained after whole-genome duplication (WGD) (Blanc and Wolfe 2004;Maere et al 2005;Blomme et al 2006).…”