Simulation of Prokaryotic Genome Evolution Subjected to Mutational Pressures Associated with DNA Replication - Biomedical Engineering Systems and Technologies - page 128

Simulation of Prokaryotic Genome Evolution Subjected
to Mutational Pressures Associated with DNA
Replication

Paweł Błazej, Paweł Mackiewicz, and Stanisław Cebrat

Department of Genomics, Faculty of Biotechnology, University of Wrocław,
ul. Przybyszewskiego 63/77, 51-148 Wrocław, Poland
[e-mail]
http://www.smorfland.uni.wroc.pl

Abstract. Each of two differently replicated DNA strands (leading and lagging)
is subjected to the distinct mutational pressure associated with its synthesis. To
simulate the influence of these pressures on the gene and genome evolution we
worked out a computer model in which protein coding sequences were mutated
according to the direct pressure (of the strand on which they were located), the
reverse pressure (of the opposite strand), and the changing pressure (when the
latter pressures were applied alternately). Simulated genomes were eliminated by
the occurrence of stop codons in the gene sequences and the loss of their cod-
ing properties. The selection against stop codons appeared more deleterious than
for coding signal. The leading strand pressure eliminated more genes because of
the coding signal loss whereas the lagging strand pressure generated more stop
codons. Generally, the reverse and changing pressures destroyed the coding sig-
nal weaker than the direct pressure.

Keywords: Coding signal, DNA asymmetry, DNA replication, Genome evolu-
tion, Monte Carlo simulation, Mutational pressure, Selection, Stop codon.

1 Introduction

Because DNA is organized in two antiparallel strands, each showing 5' to 3' direction,
and DNA polymerase can synthesize a new DNA strand only in the 5' to 3' direction,
the replication of these strands proceeds differently. One of these strands named lead-
ing, is synthesized continuously toward the replication fork movement in contrast to
the complementary lagging strand strand, that is synthesized of Okazaki fragments in
the direction opposite to the movement of the fork. The distinct mode of replication
causes that these strands are subjected to different pattern of nucleotide substitution
[1-5]. These various directional mutational pressures lead to disparate nucleotide com-
position of the differently replicated DNA strands, which is very well pronounced in
many bacterial genomes [6-13]. This compositional bias is called DNA asymmetry and
is defined as a deviation from the equality between complementary nucleotides in a sin-
gle DNA strand, i.e. [G]=[C] and [A]=[T]. The asymmetry is usually expressed as the
normalized difference in the number of complementary nucleotides in one DNA strand,
i.e. AT skew = [A-T]/[A+T] and GC skew = [G-C]/[G+C](Fig. 1).