S. Cebrat, M. R. Dudek, A. Gierlik, M. Kowalczuk P. Mackiewicz, 1999, Effect of replication on the third base of codons. Physica A, 265(1-2), 78 ? 84. (abstract)
P. Mackiewicz, A.Gierlik, M. Kowalczuk, M. R. Dudek, S. Cebrat, 1999, How does replication-associated mutational pressure influence amino acid composition of proteins? Genome Research,9(5), 409-416. (abstract)
P. Mackiewicz, A.Gierlik, M. Kowalczuk, M. R. Dudek, S. Cebrat, 1999, Asymmetry of nucleotide composition of prokaryotic chromosomes. Journal of Applied Genetics, 40(1), 1-14. (abstract)
- P. Mackiewicz, A. Gierlik, M. Kowalczuk, D. Szczepanik, M.R. Dudek,
S. Cebrat, 1999, Mechanisms generating correlation in nucleotide composition
in Borrelia burgdorferi genome. Physica A, 273, 103 -
115.
- M. Kowalczuk, A. Gierlik, P. Mackiewicz, S. Cebrat, M.R. Dudek,
1999, Optimization of Gene Sequences under Constant Mutational Pressure
and Selection. Physica A, 273, 116 - 131.
The bacterial chromosome is a double
stranded DNA molecule. Each DNA molecule is built of two antiparallel (Watson
and Crick) strands (see diagram in Fig. 1a). Each of these strands is a
directional structure with one end described as 5' and the second one as
3'. Eubacterial chromosomes usually are circular and have only one origin
of replication (where replication starts in both directions) and a termination
region, where the two replication forks meet and replication ends. DNA
synthesis is semiconservative, which means that after replication in the
new DNA molecule one strand is the old one (matrix) and the other one is
newly synthesised. Synthesis of a new strand is possible only in one direction:
from the 5' end to the 3' end. Since matrix strands are antiparallel to
the newly synthesised strands, the mechanisms of replication of the two
strands have to be different. In fact one strand is synthesised continuously
- it is called leading (blue line in Fig. 1a) and the other one is synthesised
discontinuously by joining fragments (orange, dotted line) and it is called
lagging (Okazaki et al., 1968; Kornberg and Baker, 1992). In eubacterial
circular genomes the role of the leading/lagging strand is switched at
the terminus of replication. At this point the leading strand becomes lagging
and vice versa. The same kind of topological switch is at the origin of
replication. A part of the chromosome from the origin to the terminus of
replication is called a replichore (Blattner et al., 1997). Usually the
two replichores in a eubacterial genome are approximately of the same length.
In Fig. 1a the topology of replication is shown. To understand the relations between the gene location and its relation to the structure of chromosome, the description of another process - the gene transcription - should be superimposed on the replicating chromosome. A gene is a fragment of double stranded DNA which codes for a single polypeptide chain. One strand of a gene is called the coding strand (sense strand or non-transcribed strand) and the other one non-coding, antisense or transcribed strand ? (Fig. 1c). It used to be said that a gene is located on the leading strand if its coding strand is replicated as the leading strand and the direction of transcription (also from 5? end to the 3? end of the gene) is the same as the direction of replication fork movement (gene 2 on Fig. 1b).
Different mechanisms of replication of the two DNA strands implicate different mutational pressures, which introduce specific nucleotide substitutions into newly synthesised DNA strands (Fijalkowska et al., 1998; see for review: Francino and Ochman, 1997). That is why a specific bias in DNA nucleotide composition between leading and lagging strands is observed in eubacterial chromosomes (Lobry, 1996a; Lobry, 1996b; Blattner et al., 1997; Freeman et al., 1998; Grigoriev, 1998; McLean et al., 1998; Mrazek and Karlin, 1998; Mackiewicz et al. 1999a; Mackiewicz et al. 1999b).
Replication-associated mutational pressure is not the only mechanism which introduces a compositional bias into the DNA molecule. Asymmetric nucleotide substitutions could also occur during transcription of genes (Beletskii and Bhagwat, 1996; Francino et al., 1996; Francino and Ochman, 1997; Freeman et al., 1998). Since transcription-associated mutational pressure preferentially affects the non-transcribed strand of genes, its local effect observed on one DNA strand (i.e. leading) depends on location of the gene on the chromosome while the replication-associated mutational pressure affects uniformly the whole replichore from the origin to the terminus of replication. It is relatively easily to separate the effect of replication from the effect of transcription by subtracting or adding the asymmetry of Watson (W) strand and the asymmetry of Crick (C) strand (Mackiewicz et al. 1999a; Mackiewicz et al. 1999b; Cebrat et al., 1999). See DNA walks for more details.
On the other hand, the protein coding sequences have its own asymmetry connected with their coding functions. This asymmetry is forced by selection for specific amino acid composition of coded proteins. All these mechanisms are responsible for establishing the specific "coding asymmetry" of bacterial genomes (see section Asymmetry of chromosomes in their coding properties).
Aquifex aeolicus
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Archaeoglobus fulgidus
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Bacillus subtilis
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Borrelia burgdorferi
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Chlamydia trachomatis
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Escherichia coli
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Haemophilus influenzae
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Helicobacter pylori
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Methanobacterium thermoautotrophicum
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Methanococcus jannaschii
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Mycobacterium tuberculosis
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Mycoplasma genitalium
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Mycoplasma pneumoniae
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Pyrococcus horikoshii
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Ricketsia prowazekii
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Synechocystis PCC6803
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Treponema pallidum
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