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1

Asymmetry in nucleotide composition of sense and antisense strands as a parameter for discriminating openreading frames as protein coding sequences

100%
Cebrat S.
|
|
vol. 38
|
issue 1
2-10
EN
Coding properties of yeast chromosomes were analysed and a strong asymmetry was found in nucleotide composition of sense and antisense strands. This property generates two very simple parameters [A]/[T] and [G]/[C] of the sense strand which could be used for discrimination of open reading frames as coding sequences with very high, statistically described level of significance. The paper contains a description of the method of ellipse of concentration in the two parameter space, which can close coding sequences inside, leaving a big fraction of noncoding sequences outside the ellipse.
2

Monte Carlo simulation of genome viability with paralog replacement

64%
Cebrat S., Stauffer D.
Journal of Applied Genetics
|
2002
|
vol. 43
|
issue 3
391-395
EN
Recent analyses of genome content have revealed that many single functions, even in haploid organisms, can be executed by more than one gene. As a result, experimental disruption of many individual genes does not exert lethal effects on the organism or even any visible change in the phenotype of the organism with a knockedout gene. Our analysis shows that such genetic redundancy allows for an appreciably higher mutation load in the genome simulations before the viability of the whole organism is destroyed.
3

Determination of replication initiation site

51%
Zakrzewska-Czerwinska J., Mackiewicz P., Zawilak A., Cebrat S.
Biotechnologia
|
2005
|
issue 3
91-101
EN
Initiation of bacterial chromosome replication is mediated by a single initiator protein ? DnaA which interacts specifically with multiple DnaA boxes located within the origin of replication oriC. We have applied in silico methods: DNA asymmetry, DnaA box distribution and dnaA gene location to identify the putative replication origins in bacterial chromosomes. The three methods identify the same region as a putative origin in more than half of the analyzed chromosomes. The most universal method of putative oriC identification in bacterial chromosomes is DNA asymmetry, although in some cases it is necessary to apply all three methods. Interestingly, most bacterial chromosomes exhibit an overrepresentation of DnaA boxes; they contain at least one cluster of DnaA boxes in the vicinity of the oriC region that is probably involved in controlling replication initiation.
4

Is there any mystery of ORPHANs ?

51%
Cebrat S., Dudek M., Mackiewicz P.
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|
vol. 38
|
issue 4
365-372
EN
We have analysed the coding capacity of ORFs longer than 100 codons found in the yeast genome. Comparing the parameters describing the DNA asymmetry in the set of known genes and the set of all ORFs>100 codons we have found that there are about 4700 coding ORFs in the yeast genome. Since for more than 2300 ORFs recognisable functions have been already found and for about 2000 ORFs homology to known genes has been identified - only about 400 ORFs can be considered as orphans - ORFs without any known function or homology. This finding means that there is no mystery of orphans - a paradox showing that the fraction of orphans has been growing with the growing number of genes with known functions in the yeast genome.
5

Mystery of orphan Open Reading Frames (ORFans)

51%
Mackiewicz P., Baczkowski K., Sobczynski, Cebrat S.
Biotechnologia
|
2005
|
issue 3
7-21
EN
Genomics is a new field of biology. Its fast development is caused mainly by quick progress in large-scale genome sequencing and in computer technology. In spite of a huge number of sequenced microbial genomes available in databases, their taxonomical diversity is biased and reflects the interests of researches and facility of microorganisms' isolation and culture in laboratory conditions. More than 80% of genome sequencing projects are focused on the members of Proteobacteria, Firmicutes and Actinobacteria. Environmental genome shotgun sequencing reveals that microbial diversity is much greater than we expected. Particular levels of genomic analysis, the problems and subjects of genomics are specified and described here.
6

Evolution of eukaryotic chromosomes ? from databases to computer modeling

51%
Mackiewicz D., Waga W., Cebrat S.
Biotechnologia
|
2010
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issue 4
131-145
EN
Computer simulations of chromosomes' and genomes' evolution suggest that the genes located on relatively large and densely packed chromosomes should be grouped in clusters. Clusters located on homologous chromosomes may complement their defects or they may co-operate providing selective advantage to their hosts. Since recombination inside clusters is harmful, selection leads to the uneven distribution of recombination events along chromosomes - relatively high recombination in the subtelomeric regions and low recombination in the central regions of chromosomes. Uneven distribution of recombinations enables sympatric speciation which can not be predicted by the mean field theories of evolution. Further studies of chromosome evolution require more precise data (the best ? full sequences) of many closely related genomes belonging to the same species.
7

From sequence to function ? looking for genes and their annotations

45%
Baczkowski K., Mackiewicz P., Kowalczuk M., Banaszak J., Cebrat S.
Biotechnologia
|
2005
|
issue 3
22-44
EN
Today, we have very powerful and effective machines and methods to sequence and analyze DNA sequences. Almost every week, new genomes are added to sequence databases. However, those data are useless without additional annotations. Genes need to be found and their functions defined. Experimental work is too slow to analyze each sequence of a potential gene but computational methods facilitate such analyses. Here, we review the methodology, potential problems and constraints in genes finding and their annotation. We describe some new approaches including comparative genomics.
8

New insights into phylogeny from genomic point of view

45%
Sobczynski M., Mackiewicz P., Mackiewicz D., Smolarczyk K., Cebrat S.
Biotechnologia
|
2005
|
issue 3
102-117
EN
Availability of fully sequenced genomes contributes to the development of new science named phylogenomics which opens new possibilities of phylogenetic analyses and study of genome evolution based on the whole information coded in genomic DNA. The advantages and disadvantages of the new methods are described. Despite many phenomena such as lineage-specific gene loss, gene duplication and horizontal gene transfer disturbing phylogenetic analyses, the new methods are able to extract some phylogenetic signals in the analysed genomes and construct reliable phylogenetic trees. The genome-based studies support not only the three-domain concept of Tree of Life but they identify previously undetected major clades of prokaryotes as well.
9

Asymmetry of nucleotide composition of prokaryotic chromosomes

45%
Mackiewicz P., Gierlik A., Kowalczuk M., Dudek M., Cebrat S.
Journal of Applied Genetics
|
1999
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vol. 40
|
issue 1
1-14
EN
We have analysed the causes of asymmetry in nucleotide composition of DNA complementary strands of prokaryotic chromosomes. Analysing DNA walks we have separated the effect of replication-associated processes from the effect introduced by transcription and coding functions. The asymmetry introduced by replication switches its polarity at the origin and at the terminus of replication, which is observed in both noncoding and coding sequences and varies with respect to positions in codons. Coding functions introduce very strong trends into protein coding ORFs, which are specific for each nucleotide position in the codon. Using detrended DNA walks we have eliminated the effect of coding density and we were able to distinguish between mutational pressure associated with replication and compositional bias for genes proximal and distal to the origin of replication.
10

Influence of replication on organization and evolution of bacterial genomes

45%
Kowalczuk M., Mackiewicz D., Mackiewicz P., Polak N., Cebrat S.
Biotechnologia
|
2005
|
issue 3
75-90
EN
In bacterial chromosomes, strong bias in nucleotide composition has been observed between differently replicated DNA strands (leading and lagging ones), and also in many species between the regions proximal and distal to the origin of replication (ori). This bias is also reflected in composition and distribution of genes along the chromosome. Several phenomena connected with the replication of the chromosome are responsible for such polarization, especially mutational pressure, repair mechanisms and recombinations, and also selection pressure. All these phenomena are not indifferent for gene evolution and their rearrangements which are strictly connected with the organization of bacterial chromosome.
11

High divergence rate of sequences located on different DNA strands in closely related bacterial genomes

39%
Mackiewicz P., Mackiewicz D., Kowalczuk M., Dudkiewicz M., Dudek M. R., Cebrat S.
Journal of Applied Genetics
|
2003
|
vol. 44
|
issue 4
561-584
EN
One of the common features of bacterial genomes is a strong compositional asymmetry between differently replicating DNA strands (leading and lagging). The main cause of the observed bias is the mutational pressure associated with replication. This suggests that genes translocated between differently replicating DNA strands are subjected to a higher mutational pressure, which may influence their composition and divergence rate. Analyses of groups of completely sequenced bacterial genomes have revealed that the highest divergence rate is observed for the DNA sequences that in closely related genomes are located on different DNA strands in respect to their role in replication. Paradoxically, for this group of sequences the absolute values of divergence rate are higher for closely related species than for more diverged ones. Since this effect concerns only the specific group of orthologs, there must be a specific mechanism introducing bias into the structure of chromosome by enriching the set of homologs in trans position in newly diverged species in relatively highly diverged sequences. These highly diverged sequences may be of varied nature: (1) paralogs or other fast-evolving genes under weak selection; or (2) pseudogenes that will probably be eliminated from the genome during further evolution; or (3) genes whose history after divergence is longer than the history of the genomes in which they are found. The use of these highly diverged sequences for phylogenetic analyses may influence the topology and branch length of phylogenetic trees. The changing mutational pressure may contribute to arising of genes with new functions as well.
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