A new method for assessing the effect of replication on DNA base composition asymmetry

Area of Science:

• Genomics
• Bioinformatics
• Molecular Evolution

Background:

• DNA base composition asymmetry is crucial for detecting prokaryotic replication origins and termini.
• Existing methods struggle to differentiate evolutionary mechanisms causing this asymmetry.
• Replication and transcription coorientation in prokaryotes create superimposed biases: replication-associated mutation bias and coding sequence-associated bias.

Purpose of the Study:

• To develop a new method for analyzing nucleotide composition asymmetry.
• To decouple replication-related and coding sequence-related mechanisms influencing base composition.
• To assess the contributions of these mechanisms in generating asymmetry.

Main Methods:

• Inspired by artificial chromosomal rearrangement to create perfect gene orientation bias.
• Analysis of nucleotide skews on artificially rearranged chromosomes.
• Application to all completely sequenced prokaryotic chromosomes.

Main Results:

• The proposed method effectively assesses contributions of replication and coding sequence mechanisms to base composition asymmetry.
• Replication mechanisms significantly impact base composition asymmetry in most prokaryotic species, with differential effects on GC and AT skews.
• The study found that polymerase-alpha subunits are insufficient to predict the AT skew direction on the leading strand.

Conclusions:

• The new method allows for the decoupling of replication-related and coding sequence-related mechanisms in nucleotide composition asymmetry.
• Replication plays a substantial role in shaping base composition asymmetry across prokaryotes.
• The direction of AT skew is not solely predictable by polymerase-alpha subunits.