A new study led by Algoma University faculty member Dr. Arshad Rafiq and his team of student researchers explores the hidden complexity of human genetics, offering new insight into how the body builds proteins and why the way genetic "instructions" are written matters more than formerly believed.
The study, titled Mapping the Inter- and Intra-genic Codon Usage Landscape in Homo sapiens, was recently published on bioRxiv and investigates how codon usage bias, a subtle but significant pattern in genetic coding, affects protein production, gene stability, and evolutionary conservation in humans. The paper is co-authored by Maahil Arshad, Matthew Uchmanowicz, Vanshika Rana, and Dr. Rafiq.
"Codon usage bias has been widely studied in bacteria and viruses, but much less so in humans," said Dr. Rafiq. "Our work shows that this bias plays an important regulatory role in how proteins are made, folded, and maintained, which could reshape how we interpret genetic information moving forward."
Codons are sequences of three DNA bases that encode amino acids, the building blocks of proteins. While multiple codons can code for the same amino acid, the body does not use them equally. This preference, or bias, can influence how quickly and accurately proteins are produced.
"We found that codon usage bias is significantly stronger in structured protein domains compared to flexible, disordered regions," said Dr. Rafiq. "The most frequently used codons are linked to higher tRNA gene copy numbers, which supports more efficient translation. Perhaps most intriguingly, genes with extremely biased codon usage appear to resist even so-called silent' mutations, suggesting strong evolutionary constraints at play."
These findings suggest codon usage is a powerful layer of regulation that could impact everything from mRNA stability to disease risk and drug development. Funded by Algoma University, this research builds a foundation for future work in functional genomics and the interpretation of synonymous (silent) mutations, which are increasingly linked to human health and disease.
The full paper is available online.
