RESUMEN
Several mammalian genes have originated from the domestication of retrotransposons, selfish mobile elements related to retroviruses. Some of the proteins encoded by these genes have maintained virus-like features; including self-processing, capsid structure formation, and the generation of different isoforms through -1 programmed ribosomal frameshifting. Using quantitative approaches in molecular evolution and biophysical analyses, we studied 28 retrotransposon-derived genes, with a focus on the evolution of virus-like features. By analyzing the rate of synonymous substitutions, we show that the -1 programmed ribosomal frameshifting mechanism in three of these genes (PEG10, PNMA3, and PNMA5) is conserved across mammals and originates alternative proteins. These genes were targets of positive selection in primates, and one of the positively selected sites affects a B-cell epitope on the spike domain of the PNMA5 capsid, a finding reminiscent of observations in infectious viruses. More generally, we found that retrotransposon-derived proteins vary in their intrinsically disordered region content and this is directly associated with their evolutionary rates. Most positively selected sites in these proteins are located in intrinsically disordered regions and some of them impact protein posttranslational modifications, such as autocleavage and phosphorylation. Detailed analyses of the biophysical properties of intrinsically disordered regions showed that positive selection preferentially targeted regions with lower conformational entropy. Furthermore, positive selection introduces variation in binary sequence patterns across orthologues, as well as in chain compaction. Our results shed light on the evolutionary trajectories of a unique class of mammalian genes and suggest a novel approach to study how intrinsically disordered region biophysical characteristics are affected by evolution.
Asunto(s)
Evolución Molecular , Retroelementos , Animales , Selección Genética , Mamíferos/genética , Mamíferos/virología , Proteínas Intrínsecamente Desordenadas/genética , Sistema de Lectura Ribosómico , HumanosRESUMEN
The genomes of cellular organisms display CpG and TpA dinucleotide composition biases. Such biases have been poorly investigated in dsDNA viruses. Here, we show that in dsDNA virus, bacterial, and eukaryotic genomes, the representation of TpA and CpG dinucleotides is strongly dependent on genomic G + C content. Thus, the classical observed/expected ratios do not fully capture dinucleotide biases across genomes. Because a larger portion of the variance in TpA frequency was explained by G + C content, we explored which additional factors drive the distribution of CpG dinucleotides. Using the residuals of the linear regressions as a measure of dinucleotide abundance and ancestral state reconstruction across eukaryotic and prokaryotic virus trees, we identified an important role for phylogeny in driving CpG representation. Nonetheless, phylogenetic ANOVA analyses showed that few host associations also account for significant variations. Among eukaryotic viruses, most significant differences were observed between arthropod-infecting viruses and viruses that infect vertebrates or unicellular organisms. However, an effect of viral DNA methylation status (either driven by the host or by viral-encoded methyltransferases) is also likely. Among prokaryotic viruses, cyanobacteria-infecting phages resulted to be significantly CpG-depleted, whereas phages that infect bacteria in the genera Burkolderia and Staphylococcus were CpG-rich. Comparison with bacterial genomes indicated that this effect is largely driven by the general tendency for phages to resemble the host's genomic CpG content. Notably, such tendency is stronger for temperate than for lytic phages. Our data shed light into the processes that shape virus genome composition and inform manipulation strategies for biotechnological applications.
Asunto(s)
Genoma Viral , Virus , Animales , Sesgo , Metilación de ADN/genética , Genoma Viral/genética , Filogenia , Virus/genética , Células Procariotas/química , Células Eucariotas/químicaRESUMEN
Dinucleotide biases have been widely investigated in the genomes of eukaryotes and viruses, but not in bacteria. We assembled a dataset of bacterial genomes (>15 000), which are representative of the genetic diversity in the kingdom Eubacteria, and we analyzed dinucleotide biases in relation to different traits. We found that TpA dinucleotides are the most depleted and that CpG dinucleotides show the widest dispersion. The abundances of both dinucleotides vary with genomic G + C content and show a very strong phylogenetic signal. After accounting for G + C content and phylogenetic inertia, we analyzed different bacterial lifestyle traits. We found that temperature preferences associate with the abundance of CpG dinucleotides, with thermophiles/hyperthemophiles being particularly depleted. Conversely, the TpA dinucleotide displays a bias that only depends on genomic G + C composition. Using predictions of intrinsic cyclizability we also show that CpG depletion may associate with higher DNA bendability in both thermophiles/hyperthermophiles and mesophiles, and that the former are predicted to have significantly more flexible genomes than the latter. We suggest that higher bendability is advantageous at high temperatures because it facilitates DNA positive supercoiling and that, through modulation of DNA mechanical properties, local or global CpG depletion controls genome organization, most likely not only in bacteria.