17 research outputs found
Bacterial protein interaction networks: connectivity is ruled by gene conservation, essentiality and function
Protein-protein interaction (PPI) networks are the backbone of all processes
in living cells. In this work we relate conservation, essentiality and
functional repertoire of a gene to the connectivity of the corresponding
protein in the PPI networks. Focusing on a set of 42 bacterial species with
reasonably separated evolutionary trajectories, we investigate three issues: i)
whether the distribution of connectivity values changes between PPI subnetworks
of essential and nonessential genes; ii) how gene conservation, measured both
by the evolutionary retention index (ERI) and by evolutionary pressures
(evaluated through the ratio and ENC plots) is related to the the
connectivity of the corresponding protein; iii) how PPI connectivities are
modulated by evolutionary and functional relationships, as represented by the
Clusters of Orthologous Proteins (COGs). We show that conservation,
essentiality and functional specialization of genes control in a quite
universal way the topology of the emerging bacterial PPI networks. Noteworthy,
a structural transition in the network is observed such that, for
connectivities , bacterial PPI networks are mostly populated by genes
that are conserved, essential and which, in most cases, belong to the COG
cluster J, related to ribosomal functions and to the processing of genetic
information
Codon Bias Patterns of 's Interacting Proteins
Synonymous codons, i.e., DNA nucleotide triplets coding for the same amino
acid, are used differently across the variety of living organisms. The
biological meaning of this phenomenon, known as codon usage bias, is still
controversial. In order to shed light on this point, we propose a new codon
bias index, , that is based on the competition between cognate and
near-cognate tRNAs during translation, without being tuned to the usage bias of
highly expressed genes. We perform a genome-wide evaluation of codon bias for
, comparing with other widely used indices: , , and
. We show that and capture similar information by being
positively correlated with gene conservation, measured by ERI, and
essentiality, whereas, and appear to be less sensitive to
evolutionary-functional parameters. Notably, the rate of variation of and
with ERI allows to obtain sets of genes that consistently belong to
specific clusters of orthologous genes (COGs). We also investigate the
correlation of codon bias at the genomic level with the network features of
protein-protein interactions in . We find that the most densely
connected communities of the network share a similar level of codon bias (as
measured by and ). Conversely, a small difference in codon bias
between two genes is, statistically, a prerequisite for the corresponding
proteins to interact. Importantly, among all codon bias indices, turns
out to have the most coherent distribution over the communities of the
interactome, pointing to the significance of competition among cognate and
near-cognate tRNAs for explaining codon usage adaptation
Essentiality, conservation, evolutionary pressure and codon bias in bacterial genes
Essential genes constitute the core of genes which cannot be mutated too much nor lost along the adaptive evolutionary history of a species. Natural selection is expected to be stricter on essential genes and on conserved (highly shared) genes, than on genes that are either nonessential or peculiar to a single or a few species. In order to further assess this expectation, we study here how essentiality of a gene is connected with its degree of conservation among several unrelated bacterial species, each one characterised by its own codon usage bias. Confirming previous results on E- Coli, we show the existence of a universal exponential correlation between gene essentiality and conservation in bacteria. Moreover, we show that, within each bacterial genome, there are at least two groups of functionally distinct genes, characterised by different levels of conservation and codon bias: i) a core of essential genes, mainly related to cellular information processing; ii) a set of less conserved genes with prevalent functions related to metabolism. The genes in the first group are more retained among species, are subject to a relatively purifying conservative selection and display a more selected choice of synonymous codons.The core of essential genes is close to the minimal bacterial genome, which is in the focus of recent studies in synthetic biology, though we confirm that othologues of genes that are essential in one species are not necessarily essential in other species. We also list a set of highly shared genes, which could constitute a reservoir of targets for new anti-microbial drugs
Co-evolution between Codon Usage and Protein-Protein Interaction in Bacteria
We study the correlation between the codon usage bias of genetic sequences
and the network features of protein-protein interaction (PPI) in bacterial
species. We use PCA techniques in the space of codon bias indices to show that
genes with similar patterns of codon usage have a significantly higher
probability that their encoded proteins are functionally connected and
interacting. Importantly, this signal emerges when multiple aspects of codon
bias are taken into account at the same time. The present study extends our
previous observations on E.Coli over a wide set of 34 bacteria. These findings
could allow for future investigations on the possible effects of codon bias on
the topology of the PPI network, with the aim of improving existing
bioinformatics methods for predicting protein interactions
Codon usage bias in radioresistant bacteria.
The relationship between patterns of codon usage bias (CUB), the preferential usage of synonimous nucleotide triplets encoding the same amino acid, and radioresistance was investigated int he genomes of 16 taxonomically distinct radioresistant prokaryotic organisms and in a control set of 11 non-radioresistant bacteria. The radioresistant species were found to be strongly biased towards G and C in the third synonimous codon position. ENC and neutrality plots also sugest that CUB in radioresistant bacteria is mainly affected by mutational bias. Furthermore, the availability of tRNA gene copy number was analyzed and it was found that nine radioresistant species have the sam number of tRNA gene copies for each codon. This suggests that tRNA gene copies and codon bias co-evolved in a specific way in radioresistant species
Codon Usage and Phenotypic Divergences of SARS-CoV-2 Genes
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a high mortality rate, and has spread around the world. To gain an understanding of the evolution of the newly emerging SARS-CoV-2, we herein analyzed the codon usage pattern of SARS-CoV-2. For this purpose, we compared the codon usage of SARS-CoV-2 with that of other viruses belonging to the subfamily of Orthocoronavirinae. We found that SARS-CoV-2 has a high AU content that strongly influences its codon usage, which appears to be better adapted to the human host. We also studied the evolutionary pressures that influence the codon usage of five conserved coronavirus genes encoding the viral replicase, spike, envelope, membrane and nucleocapsid proteins. We found different patterns of both mutational bias and natural selection that affect the codon usage of these genes. Moreover, we show here that the two integral membrane proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their corresponding genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins (S), although they are regarded as are important targets for the development of vaccines and antiviral drugs, tend to evolve faster in comparison to the two genes mentioned above. Overall, our results suggest that the higher divergence observed for the latter three genes could represent a significant barrier in the development of antiviral therapeutics against SARS-CoV-2
Codon Usage and Phenotypic Divergences of SARS-CoV-2 Genes.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a high mortality rate, and has spread around the world. To gain an understanding of the evolution of the newly emerging SARS-CoV-2, we herein analyzed the codon usage pattern of SARS-CoV-2. For this purpose, we compared the codon usage of SARS-CoV-2 with that of other viruses belonging to the subfamily of Orthocoronavirinae. We found that SARS-CoV-2 has a high AU content that strongly influences its codon usage, which appears to be better adapted to the human host. We also studied the evolutionary pressures that influence the codon usage of five conserved coronavirus genes encoding the viral replicase, spike, envelope, membrane and nucleocapsid proteins. We found different patterns of both mutational bias and natural selection that affect the codon usage of these genes. Moreover, we show here that the two integral membrane proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their corresponding genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins (S), although they are regarded as are important targets for the development of vaccines and antiviral drugs, tend to evolve faster in comparison to the two genes mentioned above. Overall, our results suggest that the higher divergence observed for the latter three genes could represent a significant barrier in the development of antiviral therapeutics against SARS-CoV-2
Psychological and Physical Distress in Italian People during COVID-19 Pandemic: One Year Later
The aim of this study was to evaluate the major life changes that Italian people experienced after one year of the COVID-19 pandemic. We assessed the psychological and physical impact of COVID-19 within one year of the pandemic situation, and its possible correlation with the positive COVID-19 trend in the Italian region. We invited Italian people to complete a cross-sectional, online survey within a three-week period from 14 March to 4 April 2021. The survey collected data on the participants’ stress and physical levels, attitude, perceived control, norms, personal and professional backgrounds, and place of stay in the last year. We used Student’s t-test and the software package GRETL for Windows to assess the association between the study outcome variables and the explanatory variables (stress, attitude, perceived control, and norms). All participants who declared a level of physical stress in their answer suffered from psychological stress, but not vice versa. The result to be highlighted is that this level of stress was found more in women and in the age range of 21–45 years
Temporal evolution and adaptation of SARS-CoV-2 codon usage.
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) first occurred in Wuhan (China) in December of 2019. Since the outbreak, it has accumulated mutations on its coding sequences to optimize its adaptation to the human host. The identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. Methods: In this study, we compared 320,338 SARS-CoV-2 genomes isolated from all over the world to the first sequenced genome in Wuhan, China. To this end, we analysed over time the codon usage patterns of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), RNA-dependent RNA polymerase (RdRp) and ORF1ab. Results: We found that genes coding for the proteins N and S diverged more rapidly since the outbreak by accumulating mutations. Interestingly, all genes show a deoptimization of their codon usage with respect to the human host. Our findings suggest a general evolutionary trend of SARS-CoV-2, which evolves towards a sub-optimal codon usage bias to favour the host survival and its spread. Furthermore, we found that S protein and RdRp are more subject to an increasing purifying pressure over time, which implies that these proteins will reach a lower tendency to accept mutations. In contrast, proteins N and M tend to evolve more under the action of mutational bias, thus exploring a large region of their sequence space. Conclusions: Overall, our study shed more light on the evolution of SARS-CoV-2 genes and their adaptation to humans, helping to foresee their mutation patterns and the emergence of new variants
Features of top-scoring communities.
<p>Number of nodes (<i>n</i>), community score (<i>n</i> times the internal density), mean degree 〈<i>k</i>〉, predominant COG label and percentage; then, for ERI and the codon bias indices, mean values <math><msub><mi>x</mi><mo>¯</mo><mi>c</mi></msub></math> internal to the community and <i>Z</i> scores (between square brackets). Values <i>Z</i> > 1 are reported in bold.</p