Abstract
Duplications of genes encoding highly connected and essential proteins are selected against in several species but not in human, where duplicated genes encode highly connected proteins. To understand when and how gene duplicability changed in evolution, we compare gene and network properties in four species (Escherichia coli, yeast, fly, and human) that are representative of the increase in evolutionary complexity, defined as progressive growth in the number of genes, cells, and cell types. We find that the origin and conservation of a gene significantly correlates with the properties of the encoded protein in the protein-protein interaction network. All four species preserve a core of singleton and central hubs that originated early in evolution, are highly conserved, and accomplish basic biological functions. Another group of hubs appeared in metazoans and duplicated in vertebrates, mostly through vertebrate-specific whole genome duplication. Such recent and duplicated hubs are frequently targets of microRNAs and show tissue-selective expression, suggesting that these are alternative mechanisms to control their dosage. Our study shows how networks modified during evolution and contributes to explaining the occurrence of somatic genetic diseases, such as cancer, in terms of network perturbations.
Highlights
Gene duplicability defines the propensity to retain multiple copies of a gene and varies among species and gene categories
The clarification of how the protein interaction network evolves enables us to understand the adaptation to the progressive increase in complexity and to better characterize the genes involved in diseases such as cancer
Gene and network properties changed during evolution The purpose of our analysis is to compare gene origin, conservation, and duplicability with connectivity and centrality of the encoded proteins in E. coli, S. cerevisiae, D. melanogaster, and Homo sapiens
Summary
Gene duplicability defines the propensity to retain multiple copies of a gene and varies among species and gene categories. The strict retention of one single copy of these particular gene categories is a consequence of the fragility towards dosage modifications Their duplication is deleterious because it interferes with essential cellular functions and with the fine-tuned equilibrium between formation and disruption of protein-protein interactions [6,7]. Through massive gene duplication followed by diversification of paralogs, vertebrates accommodated the expansion of gene families that are involved in regulation, signal transduction, protein transport, and protein modification [11,12]. In this context, it has been proposed that a higher connectivity may favor the functional diversification of paralogs, for example through tissue specialization [8]. A thorough analysis of which types of genes undergo modification of their duplicability during evolution and how this influences the network properties of the encoded proteins is still missing
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