Strand Asymmetry and Mutation Dynamics in Genomic Studies

Strand asymmetry arises from inherent differences in the processing of the two DNA strands during replication and transcription. The leading strand, synthesised continuously, and the lagging strand, synthesised in Okazaki fragments, experience distinct error profiles and repair dynamics. These differences manifest as biases in nucleotide composition, insertion–deletion (indel) frequencies and substitution spectra along each strand. Mutation dynamics are further modulated by repair pathways: transcription-coupled nucleotide excision repair preferentially corrects lesions on the transcribed strand, while mismatch repair acts broadly but can interact with transcription-linked processes to reinforce strand bias. Large-scale structural variations, such as inversions symmetric around the origin of replication, reflect replication-associated breakage and rejoining events that also contribute to genome evolution. Together, these phenomena influence gene organisation, genome architecture and evolutionary trajectories across organisms, with implications for cancer genomics, microbial adaptation and fundamental mechanisms of DNA maintenance.

Research from Nature Portfolio

Recent studies have dissected how transcription-coupled nucleotide excision repair and mismatch repair collaborate to shape indel distributions in human cancer genomes. By orientating indels relative to gene transcription, researchers revealed a pronounced transcriptional strand asymmetry in mononucleotide repeats and across whole-genome sequences, attributing this bias to the interplay of transcription-coupled repair and mismatch correction under physiological conditions. In bacterial systems, comparative analyses of mutational pressure matrices have shown that empirical substitution rates tend to minimise the physicochemical cost of amino acid replacements. This optimisation indicates that mutational processes have evolved to balance the generation of diversity with the preservation of protein function, thereby shaping genomic substitution biases in ways that are consistent across diverse prokaryotic lineages.

Strand Asymmetry and Mutation Dynamics in Genomic Studies publication trend

The graph below shows the total number of articles in strand asymmetry and mutation dynamics in genomic studies across all publications each year (not limited to Nature Index journals).

Technical terms

Strand asymmetry: The unequal distribution of nucleotides or mutations between the two DNA strands due to replication and repair biases.

Leading strand: The DNA strand synthesised continuously in the direction of the replication fork movement.

Lagging strand: The DNA strand synthesised discontinuously as Okazaki fragments opposite to the replication fork direction.

Transcription-coupled nucleotide excision repair (TC-NER): A DNA repair pathway that preferentially removes lesions from the transcribed strand of active genes.

Mismatch repair (MMR): A post-replicative repair mechanism that corrects base–base mismatches and small insertion–deletion loops across both strands.

Replication-associated structural rearrangements (RASRs): Large inversions or translocations in genomes that arise from replication breaks and rejoining events, often symmetric around replication origins.

References

1. Transcription-coupled repair and mismatch repair contribute towards preserving genome integrity at mononucleotide repeat tracts. Nature Communications (2020).
2. Quantitative analysis of correlation between AT and GC biases among bacterial genomes. PLOS ONE (2017).
3. Optimization of amino acid replacement costs by mutational pressure in bacterial genomes. Scientific Reports (2017).
4. Asymmetron: a toolkit for the identification of strand asymmetry patterns in biological sequences. Nucleic Acids Research (2020).
5. Replication-associated inversions are the dominant form of bacterial chromosome structural variation. Life Science Alliance (2022).