1,721,011 research outputs found
Relationships between transcriptional and translational control of gene expression in Saccharomyces cerevisiae: a multiple regression analysis
No full textUtility of JC polyomavirus in tracing the pattern of human migrations dating to prehistoric times
No full textJC virus (JCV) is a double-stranded DNA polyomavirus co-evolving with humans since the time
of their origin in Africa. JCV seems to provide new insights into the history of human populations,
as it suggests an expansion of humans from Africa via two distinct migrations, each carrying a
different lineage of the virus. A possible alternative to this interpretation could be that the
divergence between the two lineages is due to selective pressures favouring adaptation of JCV
to different climates, thus making any inference about human history debatable. In the present
study, the evolution of JCV was investigated by applying correspondence analysis to a set of
273 fully sequenced strains. The first and more important axis of ordination led to the detection
of 61 nt positions as the main determinants of the divergence between the two virus lineages.
One lineage includes strains of types 1 and 4, the other strains of types 2, 3, 7 and 8. The
distinctiveness of the Caucasian lineage (types 1 and 4), largely diffused in the northern areas
of the world, was almost entirely ascribed to synonymous substitutions. The findings provided
by the subsequent axes of ordination supported the view of an evolutionary history of JCV
characterized by genetic drift and migration, rather than by natural selection. Correspondence
analysis was also applied to a set of 156 human mitochondrial genome sequences. A detailed
comparison between the substitution patterns in JCV and mitochondria brought to light some
relevant advantages of the use of the virus in tracing human migrations
Different patterns of codon usage in the overlapping polymerase and surface genes of hepatitis B virus suggest a de novo origin by modular evolution
Full text linkThe polymerase (P) and surface (S) genes of hepatitis B virus (HBV) are the longest gene overlap in animal viruses. Gene overlaps originate by the overprinting of a novel frame onto an ancestral pre-existing frame. Identifying which frame is ancestral and which one is de novo (the genealogy of the overlap) is an appealing topic. However, the P/S overlap of HBV is an intriguing paradox, because both genes are indispensable for virus survival. Thus, the hypothesis of a primordial virus without the surface protein or without the polymerase has no biological sense. With the aim to determine the genealogy of the overlap, I compared the codon usage of the overlapping frames P and S with that of the non-overlapping region. I found that the overlap of human HBV had two patterns of codon usage. One was localized in the 5' one-third of the overlap, and the other in the 3' two-thirds. By extending the analysis to non-human HBVs, I found that this feature occurred in all hepadnaviruses. Under the assumption that the ancestral frame has a codon usage significantly closer to that of the non-overlapping region than the de novo frame, I could predict the ancestral frames in the 5' and 3' region of the overlap. They were, respectively, the frame S and the frame P. These results suggest that the spacer domain of the polymerase and the S domain of the surface protein originated de novo by overprinting. They support a modular-evolution hypothesis on the origin of the overlap
Systematic Detection of Alternative Open Reading Frames (altORFs) in Cancer Driver Genes
No full textThe discovery of translated alternative open reading frames (altORFs) in protein-coding regions has expanded the coding potential of viral, prokaryotic and eukaryotic genes. Experimental and computational approaches indicate that overlapping coding regions occur in mammals. In this study, I used a prediction method based on five criteria to detect novel altORFs in the human genes taken from the COSMIC Cancer Gene Census Database. Apart from the well characterized examples of human cancer-specific antigens expressed from altORF, the vast catalogue of nucleotide substitutions across cancer genes (the COSMIC database) is also likely to harbor previously uncharacterized altORFs. Under the five prediction criteria, I found 251 novel altORFs, 41 of which highly conserved in mammals and 60 uniquely resulting from nucleotide substitutions in the primary ORF of cancer genes. I found experimental evidence for 38% of the 251 novel altORFs from mass spectrometry and ribosome profiling databases. In particular, I found three altORFs in the proto-oncogene RET, three expressed altORfs in the isocitrate dehydrogenase-2 gene, and one expressed large altORF (498 nt) in the mutated TP53 gene. This study may offer clinical perspectives, because a potential source of cancer antigens may include antigens derived from translation of currently unannotated open reading frames. The altORFs detected in this study could be candidates for future experimental validation
Detection of signature sequences in overlapping genes and prediction of a novel overlapping gene in hepatitis G virus
No full textPattern of nucleotide substitution in the overlapping nonstructural genes of influenza A virus and implication for the genetic diversity of the H5N1 subtype
No full textIn viruses under strong pressure to minimize genome size, overlapping genes represent a fine strategy to condense a maximum amount of
information into short nucleotide sequences. Here, we investigated the evolution of the genes encoding the nonstructural proteins NS1 and NS2 of
influenzaAvirus (IAV), which are one of the best characterized cases of gene overlap. By a detailed analysis of about four hundred sequences grouped
into 11 IAV subtypes, we found that the overlapping coding region of the NS1 gene shows a significant increase of the rate of nonsynonymous
change, with respect to its nonoverlapping counterpart. The same feature was observed in the overlapping coding region of the NS2 gene. Such a
variation pattern, which implies the occurrence of several amino acid substitutions in the protein regions encoded by overlapping frames, is different
from the pattern of constrained evolution typical of other viral overlapping-gene systems. Amino acid sequence analysis of the NS1 and NS2 proteins
revealed that some nonsynonymous substitutions, located in the region of gene overlap, play a critical role in shaping the genetic diversity of the
highly pathogenic subtype H5N1. Since both proteins contribute to disease pathogenesis by affecting many virus and host-cell processes, information
provided by this study should be useful to highlight the impact of nonstructural gene variation on the pathogenicity of H5N1 viruses
Origin and evolution of overlapping genes in Microviridae
No full textThe possibility of creating novel genes from pre-existing sequences, known as overprinting, is a
widespread phenomenon in small viruses. Here, the origin and evolution of gene overlap in the
bacteriophages belonging to the family Microviridae have been investigated. The distinction
between ancestral and derived frames was carried out by comparing the patterns of codon usage in
overlapping and non-overlapping genes. By this approach, a gradual increase in complexity of
the phage genome – from an ancestral state lacking gene overlap to a derived state with a high
density of genetic information – was inferred. Genes encoding less-essential proteins, yet playing a
role in phage growth and diffusion, were predicted to be novel genes that originated by overprinting.
Evaluation of the rates of synonymous and non-synonymous substitution yielded evidence for
overlapping genes under positive selection in one frame and purifying selection in the alternative
frame
Detecting traces of prehistoric human migrations by geographic synthetic maps of Polyomavirus JC
No full textAbstract. The polyomavirus JC (JCV) is a doublestranded
DNA virus that is ubiquitous in human
populations and is excreted in urine by a large percentage
of individuals (20–70%). The strong genetic
stability, combined with a mechanism of transmission
mainly within the family, makes JCV a good marker
of human migrations. In this study, the coevolution
of JCV with its human host is investigated by using
over a thousand nucleotide sequences deposited in
the EMBL database; they correspond to the IG region,
which is the genomic region with the highest
rate of variation. The pattern of genetic diversity in
JCV is evaluated by the principal coordinates analysis
and the construction of synthetic maps. The first
principal coordinate supports the existence of two
distinct virus lineages, both arising from the ancestral
African type. The first synthetic map suggests a twomigration
model of the human dispersal out of
Africa, thus implying a more complex picture than
that known from human genes. The second principal
coordinate points out the distinctiveness of strains
coming from Asian/Amerind populations. The picture
yielded by the second synthetic map appears to
be more consistent with that known from human
genes. In fact, it provides evidence of a deep split of
the Asian lineage of JCV into two main branches: one
diffusing in Japan and Americas, the other in
Southeast Asia. The view that JCV, with its peculiar
feature of a dual early emergence from Africa, can
provide new information about the evolutionary
history of our ancestors is discussed
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