GC₃ Biology in Eukaryotes and Prokaryotes

We describe the distribution of Guanine and Cytosine (GC) content in the third codon position (GC3) distributions in different species, analyze evolutionary trends and discuss differences between genes and organisms with distinct GC3 levels. We scrutinize previously published theoretical frameworks and construct a unified view of GC3 biology in eukaryotes and prokaryotes

The footprint of metabolism in the organization of mammalian genomes

<p>Abstract</p> <p>Background</p> <p>At present five evolutionary hypotheses have been proposed to explain the great variability of the genomic GC content among and within genomes: the mutational bias, the biased gene conversion, the DNA breakpoints distribution, the thermal stability and the metabolic rate. Several studies carried out on bacteria and teleostean fish pointed towards the critical role played by the environment on the metabolic rate in shaping the base composition of genomes. In mammals the debate is still open, and evidences have been produced in favor of each evolutionary hypothesis. Human genes were assigned to three large functional categories (as well as to the corresponding functional classes) according to the KOG database: (i) information storage and processing, (ii) cellular processes and signaling, and (iii) metabolism. The classification was extended to the organisms so far analyzed performing a reciprocal Blastp and selecting the best reciprocal hit. The base composition was calculated for each sequence of the whole CDS dataset.</p> <p>Results</p> <p>The GC3 level of the above functional categories was increasing from (i) to (iii). This specific compositional pattern was found, as footprint, in all mammalian genomes, but not in frog and lizard ones. Comparative analysis of human versus both frog and lizard functional categories showed that genes involved in the metabolic processes underwent the highest GC3 increment. Analyzing the KOG functional classes of genes, again a well defined intra-genomic pattern was found in all mammals. Not only genes of metabolic pathways, but also genes involved in chromatin structure and dynamics, transcription, signal transduction mechanisms and cytoskeleton, showed an average GC3 level higher than that of the whole genome. In the case of the human genome, the genes of the aforementioned functional categories showed a high probability to be associated with the chromosomal bands.</p> <p>Conclusions</p> <p>In the light of different evolutionary hypotheses proposed so far, and contributing with different potential to the genome compositional heterogeneity of mammalian genomes, the one based on the metabolic rate seems to play not a minor role. Keeping in mind similar results reported in bacteria and in teleosts, the specific compositional patterns observed in mammals highlight metabolic rate as unifying factor that fits over a wide range of living organisms.</p

Runaway GC evolution in gerbil genomes

Recombination increases the local GC-content in genomic regions through GC-biased gene conversion (gBGC). The recent discovery of a large genomic region with extreme GC-content in the fat sand rat Psammomys obesus provides a model to study the effects of gBGC on chromosome evolution. Here, we compare the GC-content and GC-to-AT substitution patterns across protein-coding genes of four gerbil species and two murine rodents (mouse and rat). We find that the known high-GC region is present in all the gerbils, and is characterised by high substitution rates for all mutational categories (AT-to-GC, GC-to-AT and GC-conservative) both at synonymous and nonsynonymous sites. A higher AT-to-GC than GC-to-AT rate is consistent with the high GC-content. Additionally, we find more than 300 genes outside the known region with outlying values of AT-to-GC synonymous substitution rates in gerbils. Of these, over 30% are organised into at least 17 large clusters observable at the megabase-scale. The unusual GC-skewed substitution pattern suggests the evolution of genomic regions with very high recombination rates in the gerbil lineage, which can lead to a runaway increase in GC-content. Our results imply that rapid evolution of GC-content is possible in mammals, with gerbil species providing a powerful model to study the mechanisms of gBGC

Deciphering Heterogeneity in Pig Genome Assembly Sscrofa9 by Isochore and Isochore-Like Region Analyses

Background: The isochore, a large DNA sequence with relatively small GC variance, is one of the most important structures in eukaryotic genomes. Although the isochore has been widely studied in humans and other species, little is known about its distribution in pigs. Principal Findings: In this paper, we construct a map of long homogeneous genome regions (LHGRs), i.e., isochores and isochore-like regions, in pigs to provide an intuitive version of GC heterogeneity in each chromosome. The LHGR pattern study not only quantifies heterogeneities, but also reveals some primary characteristics of the chromatin organization, including the followings: (1) the majority of LHGRs belong to GC-poor families and are in long length; (2) a high gene density tends to occur with the appearance of GC-rich LHGRs; and (3) the density of LINE repeats decreases with an increase in the GC content of LHGRs. Furthermore, a portion of LHGRs with particular GC ranges (50%–51 % and 54%–55%) tend to have abnormally high gene densities, suggesting that biased gene conversion (BGC), as well as time- and energy-saving principles, could be of importance to the formation of genome organization. Conclusion: This study significantly improves our knowledge of chromatin organization in the pig genome. Correlations between the different biological features (e.g., gene density and repeat density) and GC content of LHGRs provide a uniqu

The expansion of amino-acid repeats is not associated to adaptive evolution in mammalian genes

BACKGROUND: The expansion of amino acid repeats is determined by a high mutation rate and can be increased or limited by selection. It has been suggested that recent expansions could be associated with the potential of adaptation to new environments. In this work, we quantify the strength of this association, as well as the contribution of potential confounding factors. RESULTS: Mammalian positively selected genes have accumulated more recent amino acid repeats than other mammalian genes. However, we found little support for an accelerated evolutionary rate as the main driver for the expansion of amino acid repeats. The most significant predictors of amino acid repeats are gene function and GC content. There is no correlation with expression level. CONCLUSIONS: Our analyses show that amino acid repeat expansions are causally independent from protein adaptive evolution in mammalian genomes. Relaxed purifying selection or positive selection do not associate with more or more recent amino acid repeats. Their occurrence is slightly favoured by the sequence context but mainly determined by the molecular function of the gene

GC3 biology in corn, rice, sorghum and other grasses

<p>Abstract</p> <p>Background</p> <p>The third, or wobble, position in a codon provides a high degree of possible degeneracy and is an elegant fault-tolerance mechanism. Nucleotide biases between organisms at the wobble position have been documented and correlated with the abundances of the complementary tRNAs. We and others have noticed a bias for cytosine and guanine at the third position in a subset of transcripts within a single organism. The bias is present in some plant species and warm-blooded vertebrates but not in all plants, or in invertebrates or cold-blooded vertebrates.</p> <p>Results</p> <p>Here we demonstrate that in certain organisms the amount of GC at the wobble position (GC₃) can be used to distinguish two classes of genes. We highlight the following features of genes with high GC₃content: they (1) provide more targets for methylation, (2) exhibit more variable expression, (3) more frequently possess upstream TATA boxes, (4) are predominant in certain classes of genes (e.g., stress responsive genes) and (5) have a GC₃content that increases from 5'to 3'. These observations led us to formulate a hypothesis to explain GC₃bimodality in grasses.</p> <p>Conclusions</p> <p>Our findings suggest that high levels of GC₃typify a class of genes whose expression is regulated through DNA methylation or are a legacy of accelerated evolution through gene conversion. We discuss the three most probable explanations for GC₃bimodality: biased gene conversion, transcriptional and translational advantage and gene methylation.</p

Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation

Developmental-stage-related patterns of gene expression correlate with codon usage and genomic GC content in stem cell hierarchies

Comparative genome analyses of deuterostomes: Metabolism and base composities of tunicates, fish and mammals genomes

The hypothesis that the metabolic rate could affect the base composition of genomes, i.e. the GC content, was tested along the phylogenetic line of deuterostomes, in the classes of tunicates, fish and mammals, by different approaches dictated by available data. Significant differences were found between the GC content of the completely sequenced genomes of C.intestinalis and C.savignyi. Interestingly, the increment was higher in C.savignyi in coding and non-coding regions, and mainly at the third codon positions (7% GC3). Methylation process and substitution rate were checked if responsible of the observed differences. The frequencies of CpG, CpA and TpG were no different between the two tunicates, and (even if tunicates showed a substitution rate 50% faster than that of vertebrates) the base composition was not directly affected. Multivariate analysis on codon usages showed that: i) in both species selection acts on codon usage, shaping translationally preferred codons between highly and lowly expressed genes; and ii) gene expression level affects the GC content of the two tunicate genomes. Data on the metabolic rate and the average genomic GC content were available for more than 200 teleostean species. Analyzing data according to the habitats, significant differences were found, with polar fish characterized by the highest metabolic rate and by a high GC content. A significant correlation was found between the two variables. Finally, intra-genome analyses of functional classes in more than ten mammalian genomes, confirmed the link between metabolism and GC content. In each mammalian genome, indeed, the average GC3 level was higher in genes involved in "metabolic processes". The same genome organization was not found in amphibians and reptiles, characterized by lower metabolic rates than mammals. The various approaches converged towards a coherent picture, highlighting the importance of metabolic rate as a factor shaping the base composition of genome