Integration of New Genes into Cellular Networks, and Their Structural Maturation

Abstract

It has been recently discovered that new genes can originate de novo from noncoding DNA, and several biological traits including expression or sequence composition form a continuum from noncoding sequences to conserved genes. In this article, using yeast genes I test whether the integration of new genes into cellular networks and their structural maturation shows such a continuum by analyzing their changes with gene age. I show that 1) The number of regulatory, protein-protein, and genetic interactions increases continuously with gene age, although with very different rates. New regulatory interactions emerge rapidly within a few million years, while the number of protein-protein and genetic interactions increases slowly, with a rate of 2-2.25 3 10 28 /year and 4.8 3 10 28 /year, respectively. 2) Gene essentiality evolves relatively quickly: the youngest essential genes appear in proto-genes 14 MY old. 3) In contrast to interactions, the secondary structure of proteins and their robustness to mutations indicate that new genes face a bottleneck in their evolution: proto-genes are characterized by high b-strand content, high aggregation propensity, and low robustness against mutations, while conserved genes are characterized by lower strand content and higher stability, most likely due to the higher probability of gene loss among young genes and accumulation of neutral mutations.

Evolutionary hallmarks of the human proteome: chasing the age and coregulation of protein-coding genes

“…These observations seem to indicate that house-keeping genes emerged early in evolution and are older in age, knowing that they reflect more essential and constitutive functions. The idea that gene essentiality is associated with older genes has been reported in several studies, for example on yeast [14] and mammalian genes [16]. By contrast, the observations that human tissue-specific genes had emerged later in evolution may reveal that human specific cellular or physiological roles are implemented at molecular level by the appearance of newer genes.…”

“…Phylostratigraphy is the usual methodology applied to find the origin and emergence of genes [10, 11]. Previous phylogenetic studies showed that the evolutionary history of different coding parts of the genome have relations with diseases [12], codon usage [13], essentiality, interactions [14], stemness and self-renewal [15]. Other studies have shown that older genes evolve slower [16], encode longer proteins, present higher expression levels, possess higher intron density and are subject to stronger purifying selection [17, 18].…”

Examining the Process of de Novo Gene Birth: An Educational Primer on “Integration of New Genes into Cellular Networks, and Their Structural Maturation”

“…Overall, these data support the proposed hypothesis from Carvunis et al (2012), summarized in Figure 1, for how de novo genes form. The Abrusán (2013) article is one study using fungal lineages. There are many other species with fully sequenced genomes and significant amounts of systems biology data.…”

“…8. In this study, Abrusán (2013) was limited by the data that were available, which is only on annotated genes (i.e., previously identified genes). How might this limitation skew the findings on characteristics of proto-genes?…”

“…Over time, some of these short ORFs may acquire new mutations, resulting in a longer ORF and, eventually, achieve higher levels of transcription and translation ( Figure 1D). Carvunis et al (2012) called "developing" genes in the C and D groups proto-genes (Figure 1), a term also used in the Abrusán (2013) article.…”