Exploring Codon-Anticodon Adaptation in Eukaryotes

Abstract

tRNA genes have the fundamental role of translating the genetic code during protein synthesis. Beyond solely a passive decoding role, the tRNA pool exerts selection pressures on the codon usage of organisms and the viruses that infect them because processing codons read by rare tRNAs can be slow or even erroneous. To better understand the interactions of codons and anticodons in eukaryotic species, we first investigated whether tRNAs packaged into HIV-1 particles may relate to the poor codon usage of HIV-1 genes. By comparing the codon usage of HIV-1 genes with that of its human host, we found that tRNAs decoding poorly adapted codons are overrepresented in HIV-1 virions. Because the affinity of Gag-Pol for all tRNAs is non-specific, HIV packaging is most likely passive and reflects the tRNA pool at the time of viral particle formation. Moreover, differences that we found in the codon usage between early and late genes suggest alterations in the tRNA pool are induced late in viral infection. Next, we tested whether a reduced tRNA anticodon pattern, which was called into question by predicted tRNA datasets, is maintained across eukaryotes. tRNA prediction methods are prone to falsely identifying tRNA-derived repetitive sequences as functional tRNA genes. Thus, we proposed and tested a novel approach to identify falsely predicted tRNA genes using phylogenetics. Phylogenetic analysis removed nearly all the genes deviating from the anticodon pattern, therefore the anticodon pattern is reaffirmed across eukaryotes.