Genetics Problem Spaces

Introduction Problem Spaces Codon Usage Overview Intro Exercise Research Questions Literature Resources Assignments Student Projects

Codon Usage Research Questions Question I The most commonly accepted explanation for codon bias, is that it represents an adaptation of mRNA sequences to biases in the translational machinery. For example in E. coli and yeast, there is a correlation between codon bias for a particular amino acid and the most abundant tRNA’s for that amino acid. Adams and Antoniw (2004) tested this hypothesis by analyzing the pattern of codon bias of plant viruses compared to their host cells. They were expecting that since virus mRNA’s are translated in their host cells, their sequences would have adapted to the same biases as the host mRNA. However, they report that although viruses showed codon bias, there was not a tight correlation between viral bias and host bias. They concluded that codon bias in viruses is due to mutational bias in the viruses. Can this same hypothesis be tested with animal viruses? There are several classes of animal viruses that differ in the replication of their genomes. How do different classes of animal viruses’ codon bias related to their host? What about retroviruses such as HIV, which integrate into the genome and for part of their life cycle are replicated by host replication machinery. Question II Another observation often cited as being consistent with the tRNA theory of codon bias is that highly expressed genes often show more bias than those expressed at low levels (Sheilds 1998 and others) The theory is that highly expressed genes are under more selection for optimal efficiency in translation and therefore they have more codon bias. There are new databases reporting the relative rates of gene expression at the mRNA level. Can you use these to test this hypothesis? Question III An alternative hypothesis for codon bias is that it represents adaptation to mRNA processes besides tRNA interactions. For example, researchers have noted that in eukaryotes codon bias is more severe in small mRNA’s than in large mRNA’s (Powell et al 1997, Moriyama et al 1998). This leads to the question how do large mRNA’s differ from small mRNA’s. One difference is that more nucleotides of small mRNA are near the start and stop codon than in large mRNA. Could it be that the processes of initiation and termination are selective forces resulting in codon bias? This could explain why bias is more severe in smaller than in larger mRNA. Can you test this hypothesis? Question IV In a short correspondence, Marin et al (1998) report a complex relationship between exon length and codon bias. That suggests that splicing may be a selective force that results in codon bias. How might this hypothesis be tested? Question V Urrutia and Hurst (2001) have observed that housekeeping genes show more codon bias than luxury genes. What selective force would generate this pattern of bias? How might you test your hypothesis? Question VI Lynn et al. (2001) and others have suggested that the organism’s optimal growth temperature influences codon bias of its genes, perhaps due to mutational forces or as a selective force on mRNA structure. How might you test this hypothesis?