Maria McSharry

UC Berkeley

“How do synonyms shape genetic messages?”

The genetic code uses synonyms to convey its message and, like language, synonyms are not always interchangeable. But when does a synonym-swap yield improvements? When does it yield disasters? Fluency in the grammatical rules of the genetic language equips us to better design mRNAs for vaccines, therapeutics, food production, and more.

ABSTRACT

Genomes are dynamic. In you, and the organisms all around you, DNA is being transcribed into mRNA, which is then translated into protein. In this process, known as gene expression, the nucleotide triplets (codons) that comprise genes are decoded into protein building blocks called amino acids. On average, amino acids are encoded by three different codons; in other words, codons have synonyms. As in language, synonymous codons aren’t equivalent and substituting one synonymous codon for another can impede translation, impacting protein abundance, folding, or function. But what determines whether a given substitution will be a benefit or a detriment to protein health? I am using a yeast protein related to the cystic fibrosis protein to get at this question. By substituting every codon for its synonyms in this protein, I can lay the foundation for modeling when codon substitutions might be consequential. Increasing our fluency in the grammatical rules of the genetic language empowers us to precisely design mRNAs for use in vaccines, therapeutics, food production, and more.
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