Abstract
Ongoing debates about functional importance of gene duplications have been recently intensified by a heated discussion of the “ortholog conjecture” (OC). Under the OC, which is central to functional annotation of genomes, orthologous genes are functionally more similar than paralogous genes at the same level of sequence divergence. However, a recent study challenged the OC by reporting a greater functional similarity, in terms of gene ontology (GO) annotations and expression profiles, among within-species paralogs compared to orthologs. These findings were taken to indicate that functional similarity of homologous genes is primarily determined by the cellular context of the genes, rather than evolutionary history. Subsequent studies suggested that the OC appears to be generally valid when applied to mammalian evolution but the complete picture of evolution of gene expression also has to incorporate lineage-specific aspects of paralogy. The observed complexity of gene expression evolution after duplication can be explained through selection for gene dosage effect combined with the duplication-degeneration-complementation model. This paper discusses expression divergence of recent duplications occurring before functional divergence of proteins encoded by duplicate genes.
Highlights
National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA
It was hypothesized that stoichiometric alterations of macromolecular complexes or cellular networks are responsible for dominant phenotypes, because of the existing nonlinear relationships between the genotypic and phenotypic values with which they are associated [39, 57]
Many observations described in this paper are best consistent with the following possible scenario of gene duplications: many recent gene duplications (or rather gene copy-number variations (CNVs) at the population level) have a positive effect in some tissues and/or environmental conditions, whereas they have a negative effect in some other tissues and/or environmental conditions (Figure 2) [3, 7, 21,22,23]
Summary
With the increasing availability of genomic data, it became clear that numerous gene families have diverged in function through series of duplications, including many lineagespecific expansions (or gene copy-number variations (CNVs) at the population level) identified in each of the genomes sequenced [1,2,3,4,5,6,7,8] This is not surprising taking into account that gene duplications are traditionally considered to be a major evolutionary source of new protein functions [1, 2, 6, 9]. The relative contributions of different factors to the evolution of paralogous genes after duplication remain a subject of intensive research and debate [7, 21, 24]
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