Search

Abstract Background In vertebrates, most protein-coding genes have a peak of GC-content near their 5′ transcriptional start site (TSS). This feature promotes both the efficient nuclear export and translation of mRNAs. Despite the importance of GC-content for RNA metabolism, its general features, origin, and maintenance remain mysterious. We investigate the evolutionary forces shaping GC-content at the transcriptional start site (TSS) of genes through both comparative genomic analysis of nucleotide substitution rates between different species and by examining human de novo mutations. Results Our data suggests that GC-peaks at TSSs were present in the last common ancestor of amniotes, and likely that of vertebrates. We observe that in apes and rodents, where recombination is directed away from TSSs by PRDM9, GC-content at the 5′ end of protein-coding gene is currently undergoing mutational decay. In canids, which lack PRDM9 and perform recombination at TSSs, GC-content at the 5′ end of protein-coding is increasing. We show that these patterns extend into the 5′ end of the open reading frame, thus impacting synonymous codon position choices. Conclusions Our results indicate that the dynamics of this GC-peak in amniotes is largely shaped by historic patterns of recombination. Since decay of GC-content towards the mutation rate equilibrium is the default state for non-functional DNA, the observed decrease in GC-content at TSSs in apes and rodents indicates that the GC-peak is not being maintained by selection on most protein-coding genes in those species.

Let [Formula: see text] be a non-chain ring of characteristic 4, where [Formula: see text] and [Formula: see text]. In this article, we discuss reversible cyclic codes of odd lengths over the ring [Formula: see text]. We construct bijections between the elements of the ring [Formula: see text] and DNA-[Formula: see text] bases for k = 1, 2 in such a manner that the reversibility problem is solved. Employing these bijections, reversible complement cyclic codes of odd lengths are generated. Furthermore, we construct a Gray map [Formula: see text] and as an application of the Gray map Φ, we obtain the GC-content of cyclic codes of arbitrary odd length over the ring [Formula: see text]. Meanwhile, we provide some examples of reversible cyclic codes of odd lengths over the ring [Formula: see text] for different values of k, and also obtain the Lee distances of these codes.

The assay for transposase-accessible chromatin using sequencing (ATAC-seq) allows the study of epigenetic regulation of gene expression by assessing chromatin configuration for an entire genome. Despite its popularity, there have been limited studies investigating the analytical challenges related to ATAC-seq data, with most studies leveraging tools developed for bulk transcriptome sequencing. Here, we show that GC-content effects are omnipresent in ATAC-seq datasets. Since the GC-content effects are sample specific, they can bias downstream analyses such as clustering and differential accessibility analysis. We introduce a normalization method based on smooth-quantile normalization within GC-content bins and evaluate it together with 11 different normalization procedures on 8 public ATAC-seq datasets. Accounting for GC-content effects in the normalization is crucial for common downstream ATAC-seq data analyses, improving accuracy and interpretability. Through case studies, we show that exploratory data analysis is essential to guide the choice of an appropriate normalization method for a given dataset.

To assist in the speed and accuracy of designing brick-based DNA nanostructures, we introduce a lightweight software suite 3DNA that can be used to generate complex structures. Currently, implementation of this fabrication strategy involves working with generalized, typically commercial CAD software, ad-hoc sequence-generating scripts, and visualization software, which must often be integrated together with an experimental lab setup for handling the hundreds or thousands of constituent DNA sequences. 3DNA encapsulates the solutions to these challenges in one package by providing a customized, easy-to-use molecular canvas and back-end functionality to assist in both visualization and sequence design. The primary motivation behind this software is enabling broader use of the brick-based method for constructing rigid, 3D DNA-based nanostructures, first introduced in 2012. 3DNA is developed to provide a streamlined, real-time workflow for designing and implementing this type of 3D nanostructure by integrating different visualization and design modules. Due to its cross-platform nature, it can be used on the most popular desktop environments, i.e., Windows, Mac OS X, and various flavors of Linux. 3DNA utilizes toolbar-based navigation to create a user-friendly GUI and includes a customized feature to analyze the constituent DNA sequences. Finally, the oligonucleotide sequences themselves can either be created on the fly by a random sequence generator, or selected from a pre-existing set of sequences making up a larger molecular canvas. [ABSTRACT FROM AUTHOR]

MicroRNAs are small RNAs that regulate gene expression through complementary base pairing with their target mRNAs. A substantial understanding of microRNA target recognition and repression mechanisms has been reached using diverse empirical and bioinformatic approaches, primarily in vitro biochemical or cell culture perturbation settings. We sought to determine if rules of microRNA target efficacy could be inferred from extensive gene expression data of human tissues. A transcriptome-wide assessment of all the microRNA–mRNA canonical interactions' efficacy was performed using a normalized Spearman correlation (Z-score) between the abundance of the transcripts in the PRAD-TCGA dataset tissues (RNA-seq mRNAs and small RNA-seq for microRNAs, 546 samples). Using the Z-score of correlation as a surrogate marker of microRNA target efficacy, we confirmed hallmarks of microRNAs, such as repression of their targets, the hierarchy of preference for gene regions (3′UTR > CDS > 5′UTR), and seed length (6 mer < 7 mer < 8 mer), as well as the contribution of the 3′-supplementary pairing at nucleotides 13–16 of the microRNA. Interactions mediated by 6 mer + supplementary showed similar inferred repression as 7 mer sites, suggesting that the 6 mer + supplementary sites may be relevant in vivo. However, aggregated 7 mer-A1 seeds appear more repressive than 7 mer-m8 seeds, while similar when pairing possibilities at the 3′-supplementary sites. We then examined the 3′-supplementary pairing using 39 microRNAs with Z-score-inferred repressive 3′-supplementary interactions. The approach was sensitive to the offset of the bridge between seed and 3′-supplementary pairing sites, and the pattern of offset-associated repression found supports previous findings. The 39 microRNAs with effective repressive 3′supplementary sites show low GC content at positions 13–16. Our study suggests that the transcriptome-wide analysis of microRNA–mRNA correlations may uncover hints of microRNA targeting determinants. Finally, we provide a bioinformatic tool to identify microRNA–mRNA candidate interactions based on the sequence complementarity of the seed and 3′-supplementary regions. [ABSTRACT FROM AUTHOR]

Deoxyribonucleic acid (DNA) is an attractive medium for long-term digital data storage due to its extremely high storage density, low maintenance cost and longevity. However, during the process of synthesis, amplification and sequencing of DNA sequences with homopolymers of large run-length, three different types of errors, namely, insertion, deletion and substitution errors frequently occur. Meanwhile, DNA sequences with large imbalances between GC and AT content exhibit high dropout rates and are prone to errors. These limitations severely hinder the widespread use of DNA-based data storage. In order to reduce and correct these errors in DNA storage, this paper proposes a novel coding schema called DNA-LC , which converts binary sequences into DNA base sequences that satisfy both the GC balance and run-length constraints. Furthermore, our coding mode is able to detect and correct multiple errors with a higher error correction capability than the other methods targeting single error correction within a single strand. The decoding algorithm has been implemented in practice. Simulation results indicate that our proposed coding scheme can offer outstanding error protection to DNA sequences. The source code is freely accessible at https://github.com/XiayangLi2301/DNA. [ABSTRACT FROM AUTHOR]

The family Chamaeleonidae comprises 228 species, boasting an extensive geographic spread and an array of evolutionary novelties and adaptations, but a paucity of genetic and molecular analyses. Veiled chameleon ( Chamaeleo calyptratus ) has emerged as a tractable research organism for the study of squamate early development and evolution. Here we report a chromosomal-level assembly and annotation of the veiled chameleon genome. We note a remarkable chromosomal conservation across squamates, but comparisons to more distant genomes reveal GC peaks correlating with ancestral chromosome fusion events. We subsequently identified the XX/XY region on chromosome 5, confirming environmental-independent sex determination in veiled chameleons. Furthermore, our analysis of the Hox gene family indicates that veiled chameleons possess the most complete set of 41 Hox genes, retained from an amniote ancestor. Lastly, the veiled chameleon genome has retained both ancestral paralogs of the Nodal gene, but is missing Dand5 and several other genes, recently associated with the loss of motile cilia during the establishment of left-right patterning. Thus, a complete veiled chameleon genome provides opportunities for novel insights into the evolution of reptilian genomes and the molecular mechanisms driving phenotypic variation and ecological adaptation.

Analysis of genome variation provides insights into mechanisms in genome evolution. This is increasingly appreciated with the rapid growth of genomic data. Mitochondrial genomes (mitogenomes) are well known to vary substantially in many genomic aspects, such as genome size, sequence context, nucleotide base composition and substitution rate. Such substantial variation makes mitogenomes an excellent model system to study the mechanisms dictating mitogenome variation. Recent sequencing efforts have not only covered a rich number of yeast species but also generated genomes from abundant strains within the same species. The rich yeast genomic data have enabled detailed investigation from genome variation into molecular mechanisms in genome evolution. This mini-review highlights some recent progresses in yeast mitogenome studies. [ABSTRACT FROM AUTHOR]

Purpose: Strategy for improving the production of biopharmaceutical protein continues to develop due to increasing market demand. Human granulocyte colony stimulating factor (hG-CSF) is one of biopharmaceutical proteins that has many applications, and easily produced in Escherichia coli expression system. Previous studies reported that codon usage, rare codon, mRNA folding and GC-content at 5’-terminal end were crucial for protein production in E. coli. In the present study, the effect of reducing the GC-content and increasing the mRNA folding free energy at the 5’-terminal end on the expression level of hG-CSF proteins was investigated. Methods: Synonymous codon substitutions were performed to generate mutant variants of open reading frame (ORF) with lower GC-content at 5’-terminal ends. Oligoanalyzer tool was used to calculate the GC content of eight codons sequence after ATG. Whereas, mRNA folding free energy was predicted using KineFold and RNAfold tools. The template DNA was amplified using three variant forward primers and one same reverse primer. Those DNA fragments were individually cloned into pJexpress414 expression vector and were confirmed using restriction and DNA sequencing analyses. The confirmed constructs were transformed into E. coli NiCo21(DE3) host cells and the recombinant protein was expressed using IPTG-induction. Total protein obtained were characterized using SDS-PAGE, Western blot and ImageJ software analyses. Results: The result showed that the mutant variant with lower GC-content and higher mRNA folding free energy near the translation initiation region (TIR) could produce a higher amount of hG-CSF proteins compared to the original gene sequence. Conclusion: This study emphasized the important role of the nucleotide composition immediately downstream the start codon to achieve high-yield protein product on heterologous expression in E. coli.

Analysis of genome variation provides insights into mechanisms in genome evolution. This is increasingly appreciated with the rapid growth of genomic data. Mitochondrial genomes (mitogenomes) are well known to vary substantially in many genomic aspects, such as genome size, sequence context, nucleotide base composition and substitution rate. Such substantial variation makes mitogenomes an excellent model system to study the mechanisms dictating mitogenome variation. Recent sequencing efforts have not only covered a rich number of yeast species but also generated genomes from abundant strains within the same species. The rich yeast genomic data have enabled detailed investigation from genome variation into molecular mechanisms in genome evolution. This mini-review highlights some recent progresses in yeast mitogenome studies.

MicroRNAs are small RNAs that regulate gene expression through complementary base pairing with their target mRNAs. A substantial understanding of microRNA target recognition and repression mechanisms has been reached using diverse empirical and bioinformatic approaches, primarily in vitro biochemical or cell culture perturbation settings. We sought to determine if rules of microRNA target efficacy could be inferred from extensive gene expression data of human tissues. A transcriptome-wide assessment of all the microRNA–mRNA canonical interactions’ efficacy was performed using a normalized Spearman correlation (Z-score) between the abundance of the transcripts in the PRAD-TCGA dataset tissues (RNA-seq mRNAs and small RNA-seq for microRNAs, 546 samples). Using the Z-score of correlation as a surrogate marker of microRNA target efficacy, we confirmed hallmarks of microRNAs, such as repression of their targets, the hierarchy of preference for gene regions (3′UTR > CDS > 5′UTR), and seed length (6 mer < 7 mer < 8 mer), as well as the contribution of the 3′-supplementary pairing at nucleotides 13–16 of the microRNA. Interactions mediated by 6 mer + supplementary showed similar inferred repression as 7 mer sites, suggesting that the 6 mer + supplementary sites may be relevant in vivo. However, aggregated 7 mer-A1 seeds appear more repressive than 7 mer-m8 seeds, while similar when pairing possibilities at the 3′-supplementary sites. We then examined the 3′-supplementary pairing using 39 microRNAs with Z-score-inferred repressive 3′-supplementary interactions. The approach was sensitive to the offset of the bridge between seed and 3′-supplementary pairing sites, and the pattern of offset-associated repression found supports previous findings. The 39 microRNAs with effective repressive 3′supplementary sites show low GC content at positions 13–16. Our study suggests that the transcriptome-wide analysis of microRNA–mRNA correlations may uncover hints of microRNA targeting determinants. Finally, we provide a bioinformatic tool to identify microRNA–mRNA candidate interactions based on the sequence complementarity of the seed and 3′-supplementary regions.

The genetic material of the three domains of life (Bacteria, Archaea, and Eukaryota) is always double-stranded DNA, and their GC content (molar content of guanine plus cytosine) varies between ≈ 13% and ≈ 75%. Nucleotide composition is the simplest way of characterizing genomes. Despite this simplicity, it has several implications. Indeed, it is the main factor that determines, among other features, dinucleotide frequencies, repeated short DNA sequences, and codon and amino acid usage. Which forces drive this strong variation is still a matter of controversy. For rather obvious reasons, most of the studies concerning this huge variation and its consequences, have been done in free-living organisms. However, no recent comprehensive study of all known viruses has been done (that is, concerning all available sequences). Viruses, by far the most abundant biological entities on Earth, are the causative agents of many diseases. An overview of these entities is important also because their genetic material is not always double-stranded DNA: indeed, certain viruses have as genetic material single-stranded DNA, double-stranded RNA, single-stranded RNA, and/or retro-transcribing. Therefore, one may wonder if what we have learned about the evolution of GC content and its implications in prokaryotes and eukaryotes also applies to viruses. In this contribution, we attempt to describe compositional properties of ∼ 10,000 viral species: base composition (globally and according to Baltimore classification), correlations among non-coding regions and the three codon positions, and the relationship of the nucleotide frequencies and codon usage of viruses with the same feature of their hosts. This allowed us to determine how the base composition of phages strongly correlate with the value of their respective hosts, while eukaryotic viruses do not (with fungi and protists as exceptions). Finally, we discuss some of these results concerning codon usage: reinforcing previous results, we found that phages and hosts exhibit moderate to high correlations, while for eukaryotes and their viruses the correlations are weak or do not exist.

We propose coding techniques that simultaneously limit the length of homopolymers runs, ensure the GC-content constraint, and are capable of correcting a single edit error in strands of nucleotides in DNA-based data storage systems. In particular, for given ℓ, ε > 0, we propose simple and efficient encoders/decoders that transform binary sequences into DNA base sequences (codewords), namely sequences of the symbols A, T, C and G, that satisfy all of the following properties: 1) runlength constraint: the maximum homopolymer run in each codeword is at most ℓ ; 2) GC-content constraint: the GC-content of each codeword is within [0.5−ε, 0.5 + ε] ; 3) error-correction: each codeword is capable of correcting a single deletion, or single insertion, or single substitution error. While various combinations of these properties have been considered in the literature, this work provides generalizations of codes constructions that satisfy all the properties with arbitrary parameters of ℓ and ε. Furthermore, for practical values of ℓ and ε, we show that our encoders achieve higher rates than existing results in the literature and approach capacity. Our methods have low encoding/decoding complexity and limited error propagation. [ABSTRACT FROM AUTHOR]

The genetic material of the three domains of life (Bacteria, Archaea, and Eukaryota) is always double-stranded DNA, and their GC content (molar content of guanine plus cytosine) varies between ≈ 13% and ≈ 75%. Nucleotide composition is the simplest way of characterizing genomes. Despite this simplicity, it has several implications. Indeed, it is the main factor that determines, among other features, dinucleotide frequencies, repeated short DNA sequences, and codon and amino acid usage. Which forces drive this strong variation is still a matter of controversy. For rather obvious reasons, most of the studies concerning this huge variation and its consequences, have been done in free-living organisms. However, no recent comprehensive study of all known viruses has been done (that is, concerning all available sequences). Viruses, by far the most abundant biological entities on Earth, are the causative agents of many diseases. An overview of these entities is important also because their genetic material is not always double-stranded DNA: indeed, certain viruses have as genetic material single-stranded DNA, double-stranded RNA, single-stranded RNA, and/or retro-transcribing. Therefore, one may wonder if what we have learned about the evolution of GC content and its implications in prokaryotes and eukaryotes also applies to viruses. In this contribution, we attempt to describe compositional properties of ∼ 10,000 viral species: base composition (globally and according to Baltimore classification), correlations among non-coding regions and the three codon positions, and the relationship of the nucleotide frequencies and codon usage of viruses with the same feature of their hosts. This allowed us to determine how the base composition of phages strongly correlate with the value of their respective hosts, while eukaryotic viruses do not (with fungi and protists as exceptions). Finally, we discuss some of these results concerning codon usage: reinforcing previous results, we found that phages and hosts exhibit moderate to high correlations, while for eukaryotes and their viruses the correlations are weak or do not exist. [ABSTRACT FROM AUTHOR]

Insect mitochondrial DNA (mtDNA) ranges from 14 to 19 kbp, and the size difference is attributed to the AT-rich control region. Jewel wasps have a parasitoid lifestyle, which may affect mitochondria function and evolution. We sequenced, assembled, and annotated mitochondrial genomes in Nasonia and outgroup species. Gene composition and order are conserved within Nasonia , but they differ from other parasitoids by two large inversion events that were not reported before. We observed a much higher substitution rate relative to the nuclear genome and mitochondrial introgression between N. giraulti and N. oneida , which is consistent with previous studies. Most strikingly, N. vitripennis mtDNA has an extremely long control region (7665 bp), containing twenty-nine 217 bp tandem repeats and can fold into a super-cruciform structure. In contrast to tandem repeats commonly found in other mitochondria, these high-copy repeats are highly conserved (98.7% sequence identity), much longer in length (approximately 8 Kb), extremely GC-rich (50.7%), and CpG-rich (percent CpG 19.4% vs. 1.1% in coding region), resulting in a 23 kbp mtDNA beyond the typical size range in insects. These N. vitripennis -specific mitochondrial repeats are not related to any known sequences in insect mitochondria. Their evolutionary origin and functional consequences warrant further investigations. [ABSTRACT FROM AUTHOR]

Abstract We propose to evaluate genome similarity by combining discrete non-decimated wavelet transform (NDWT) and elastic net. The wavelets represent a signal with levels of detail, that is, hidden components are detected by means of the decomposition of this signal, where each level provides a different characteristic. The main feature of the elastic net is the grouping of correlated variables where the number of predictors is greater than the number of observations. The combination of these two methodologies applied in the clustering analysis of the Mycobacterium tuberculosis genome strains proved very effective, being able to identify clusters at each level of decomposition.

Purpose: Strategy for improving the production of biopharmaceutical protein continues to develop due to increasing market demand. Human granulocyte colony stimulating factor (hGCSF) is one of biopharmaceutical proteins that has many applications, and easily produced in Escherichia coli expression system. Previous studies reported that codon usage, rare codon, mRNA folding and GC-content at 5'-terminal end were crucial for protein production in E. coli. In the present study, the effect of reducing the GC-content and increasing the mRNA folding free energy at the 5'-terminal end on the expression level of hG-CSF proteins was investigated. Methods: Synonymous codon substitutions were performed to generate mutant variants of open reading frame (ORF) with lower GC-content at 5'-terminal ends. Oligoanalyzer tool was used to calculate the GC content of eight codons sequence after ATG. Whereas, mRNA folding free energy was predicted using KineFold and RNAfold tools. The template DNA was amplified using three variant forward primers and one same reverse primer. Those DNA fragments were individually cloned into pJexpress414 expression vector and were confirmed using restriction and DNA sequencing analyses. The confirmed constructs were transformed into E. coli NiCo21(DE3) host cells and the recombinant protein was expressed using IPTG-induction. Total protein obtained were characterized using SDS-PAGE, Western blot and ImageJ software analyses. Results: The result showed that the mutant variant with lower GC-content and higher mRNA folding free energy near the translation initiation region (TIR) could produce a higher amount of hG-CSF proteins compared to the original gene sequence. Conclusion: This study emphasized the important role of the nucleotide composition immediately downstream the start codon to achieve high-yield protein product on heterologous expression in E. coli. [ABSTRACT FROM AUTHOR]

Identification of regulatory elements is essential for understanding the mechanism behind regulating gene expression. These regulatory elements—located in or near gene—bind to proteins called transcription factors to initiate the transcription process. Their occurrences are influenced by the GC-content or nucleotide composition. For generating synthetic coding sequences with pre-specified amino acid sequence and desired GC-content, there exist two stochastic methods, multinomial and maximum entropy. Both methods rely on the probability of choosing the codon synonymous for usage in regard to a specific amino acid. In spite the latter exhibited unbiased manner, the produced sequences are not exactly obeying the GC-content constraint. In this paper, we present an algorithmic solution to produce coding sequences that follow exactly a primary amino acid sequence and a desired GC-content. The proposed tool, namely CodSeqGen, depends on random selection for smaller subsets to be traversed using the backtracking approach. • Generating random coding sequence is computationally expensive. • For proteins of length n , we need to test 6 n coding sequences to find those satisfying GC-content constraints. • CodSeqGen uses smart backtracking, and produces synonymous coding sequences with the exact desired GC-contents. • Experiments show CodSeqGen produces sequences with GC-contents that satisfy the constraints while NullSeq does not. [ABSTRACT FROM AUTHOR]

Histone modifications play critical roles in mammalian development, regulating chromatin structure and gene expression. Dynamic histone modifications among cell types have been shown to associate with changes in mammalian development. However, how to quantitatively measure the histone modification alterations and how histone modifications vary across cell types under different genetic contexts remain largely unexplored and whether these changes are related to the primary DNA sequence remains limited. Here, we employed an entropy-based method to measure histone modification alterations in six definite genomic regions across five cell types and identified lineage-specific histone modification genes. We observed that histone modification alterations prefer to enrich in 5′-UTR exons, and also in 3′-UTR exons and its downstream. Then we built a model to predict the histone modification patterns from the primary DNA sequence. We found that the frequencies of k-mer sequence compositions are predictive of histone modification patterns, suggesting that the primary DNA sequence correlated with the histone modification alterations among cell types. Additionally, the lineage-specific histone modification genes display a higher conservation and lower GC-content. Together, we performed a systematic analysis for histone modification alterations and demonstrated how to identify genomic region-specific elements of epigenetic and genetic regulation and histone modification patterns across different cell types. [ABSTRACT FROM AUTHOR]

The division of the cellular space into nucleoplasm and cytoplasm promotes quality control mechanisms that prevent misprocessed mRNAs and junk RNAs from gaining access to the translational machinery. Here, we explore how properly processed mRNAs are distinguished from both misprocessed mRNAs and junk RNAs by the presence or absence of various 'identity features'.

We develop the theory for constructing DNA cyclic codes of odd length over R = Z 4 [ u ] / 〈 u 2 − 1 〉 based on the deletion distance. Cyclic codes of odd length over R satisfying the reverse constraint and the reverse-complement constraint are discussed. The GC -content of these codes and their deletion distance are studied. Among others, examples of cyclic DNA codes with GC -content and their respective deletion distance are provided. [ABSTRACT FROM AUTHOR]

In this paper, we construct linear codes over Z 4 with bounded GC-content. The codes are obtained using a greedy algorithm over Z 4 . Further, upper and lower bounds are derived for the maximum size DNA codes of length n with constant GC-content w and edit distance d. [ABSTRACT FROM AUTHOR]

The presence of H3K27me3 has been demonstrated to correlate with the CpG content. In this work, we tested whether H3K27ac has similar sequence preferences. We performed a translocation of DNA sequences with various properties into a beta-globin locus to control for the local chromatin environment. Our results suggest that in contrast to H3K27me3, H3K27ac gain is unlikely affected by the CpG content of the underlying DNA sequence, while extremely high GC-content might contribute to the gain of the H3K27ac.

The presence of H3K27me3 has been demonstrated to correlate with the CpG content. In this work, we tested whether H3K27ac has similar sequence preferences. We performed a translocation of DNA sequences with various properties into a beta globin locus to control for the local chromatin environment. We demonstrate that H3K27ac is not linked to CpG content of the sequence, while extremely high GC-content may contribute to the establishment of this mark.

Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. In animals, the population genetics of codon usage bias has only been studied in a handful of model organisms so far, and can be affected by confounding, nonadaptive processes such as GC-biased gene conversion and experimental artefacts. Using population transcriptomics data, we analyzed the relationship between codon usage, gene expression, allele frequency distribution, and recombination rate in 30 nonmodel species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased gene conversion on codon usage by separately analyzing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons tend to be preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased gene conversion, which is widespread in animals and the main force determining the fate of T↔GCmutations. Intriguingly, the strength of its effect was uncorrelated with Ne. [ABSTRACT FROM AUTHOR]

Nhp6A is a small nonhistone chromosomal yeast protein that binds DNA nonspecifically. This protein is present at many promoters and transcribed regions of the genome and is involved in regulation of transcription. Recently, Nhp6A was shown to participate in destabilization of the nucleosome structure. This may explain its location at regulatory sites. However, its function in the coding regions remains unknown. In this study, in order to identify the mechanisms of Nhp6A action, we examined genomic associations of the Nhp6A protein along the entire length of the target genes, including the open reading frame. We found that Nhp6A predominantly binds to the coding regions of short GC-rich yeast genes. The observed interaction is not associated with the high GC content in these DNA loci. Thus, we can propose a specific regulatory mechanism involving Nhp6A for this group. Since a large number of the studied genes retain features of the ancestral bacterial genome, we suggest that this group can be defined as “ancient.” Presumably, this genomic distribution of Nhp6 is related to the mechanisms of regulation of gene transcription that appeared early in the course of evolution. [ABSTRACT FROM AUTHOR]