Adhere to a biological perspective: scientists propose a framework to highlight the importance of internal constraints on prokaryotic genome evolution

BEIJING— Understanding how prokaryotic genomes coordinate nucleotide composition and gene distribution is a central yet unresolved question in genome evolution. Across different genomes, GC-content, nucleotide asymmetries, and biased gene distribution between replication strands are tightly associated, but existing explanations typically address only individual components and lack a unified causal framework.

In a study published in Journal of Systematics and Evolution, scientists from Sun Yat-sen University propose a novel framework to illustrate the evolution of prokaryotic genome organization. In this framework, the negative correlations between GC-content and the GC- and AT-skews of protein-coding genes constitute a critical nexus for genome organization. Both the GC-skew and AT-skew of coding genes increase as GC-content decreases. This trend is mostly determined by synonymous substitutions, because of the structure of the genetic code, and by nonsynonymous substitutions, likely owing to selective constraints on the hydrophobic core of proteins, respectively. Consequently, an increasing number of protein-coding genes has been transferred from the lagging to the leading strand at low GC-content, largely to avoid deleterious mutations as well as head-on collisions, which gives rise to high GS-bias.

"For traits spanning large phylogenetic scales, the pursuit of an environment-specific explanation should not be the primary concern; instead, a fundamental biological perspective should be upheld," says Dr. Wenkai Teng, first author of the study.

The study integrates previously proposed hypotheses to explain the variations in GC-content, GC-skew, AT-skew, and GS-bias. These genome features are all phylogenetically conserved and are tightly associated with each other. The evolutionary framework is proposed according to several fundamental aspects of prokaryotic genomes. First, the strong agreement in base composition between coding sequences and non-coding sequences demonstrates that the vast variations in genomic GC-content primarily derive from mutational biases, although environmental pressures may also exert an influence. Second, on account of the specific structure of the universal genetic code, GC-content, GC-skew, and AT-skew should not be independent of each other, at least in protein-coding genes. Third, genes on both the leading and the lagging strands exhibit positive AT-skew at low GC-content, and AT-skew is higher at non-synonymous sites, suggesting the involvement of constraints from protein evolution. Finally, similar to GC-content, the agreement in nucleotide skews between coding genes and non-coding sequences indicates that mutational biases likely play a significant role in promoting the evolution of an atypical organizational pattern.

"This study highlights the importance of fundamental biological constraints on genome evolution, such as the structure of the genetic code, protein folding, and mutational biases likely imposed by DNA replication and repair," adds Prof. Lingling Zheng, a corresponding author of the study.

The study explains why atypical organization emerges primarily in low-GC genomes, reveals that mutational biases likely evolved to accommodate the skew requirements of coding genes, and highlights the importance of internal constraints on prokaryotic genome evolution.

Original Source:

Teng, Wenkai, Zhou, Xiaofeng, Qu, Lianghu, Feng, Xiao and Zheng, Lingling (2026), Genomic coordination of nucleotide skews and gene strand distribution driven by GC-content in prokaryotes. Journal of Systematics and Evolution. https://doi.org/10.1111/jse.70093

Keywords:

GC-content, gene distribution, genetic code, genome organization, nucleotide skew, prokaryotes.

Author’s Institution:

State Key Laboratory for Biocontrol, Innovation Center for Evolutionary Synthetic Biology, Guangdong Provincial Key Laboratory of Plant Stress Biology, School of Agriculture and Biotechnology, Sun Yat-sen University Shenzhen Campus.

About JSE:

Journal of Systematics and Evolution (JSE) is a peer-reviewed, bi-monthly international English-language journal dedicated to the understanding of biodiversity and evolution. Papers in any of the following and related fields will be considered: systematics and biodiversity conservation, paleobiology and biogeography, adaptation, speciation and domestication, evolutionary genomics and Evo-Devo, theory and methods in evolutionary biology.