- Email: [email protected]
Codon-preference riddles
JOURNAL CLUB
staining shifts to a diffuse nuclear pattern. In quantitative CHIP, this is accompanied by a decrease in telomere association and a significant increase in binding proximal to DSBs. Remarkably, the introduction of a single DSB using the HO endonuclease can trigger the complete translocation response, implying it is an active process. Here, Ku relocalization is more rapid and transient than Sir relocalization, which per-
sists for several hours. Relocalization requires the RAD9 and MEC1 checkpoint genes, and only occurs during S phase but is reversible as cells move into G2. The picture emerging is that telomeres might be a sink for preassembled NHEJ repair complexes. In response to damage signals, Ku might rapidly scan the chromosome to locate and bind to the DSBs. Recruited Sir proteins could
Codon-preference riddles The genetic code is redundant but different codons are nonetheless used to different extents. Although this is a common observation for many genes, the mystery of how this comes about is intriguing. Optimal codons can help to achieve translational efficiency and accuracy and it is often thought that this reflects differences in the tRNA pool size. However, the riddle then is why there should be such differences in tRNA pool size. Antezana and Kreitman1 now take a completely different look at this by proposing that there are generally preferred duplet and triplet motifs in DNA and/or RNA, and that codon-usage preferences are only a secondary adaptation to these preferred motifs. They test this assumption with an algorithm that searches for such motifs, not only within but also outside of, the reading frames. This analysis reveals that there are, indeed, preferences outside of the frames that match
those found within the frames. Although the overlap is not complete, the authors suggest that there is a complex interplay between preferred di- and trinucleotide motifs that, in combination, dictate the codon preferences. Thus, different t-RNA pool sizes would be a secondary adaptation to these compositional constraints, rather than the driving force. Musto et al.2 have studied a different type of compositional constraint, namely codon usage in the genome of the parasite Plasmodium falciparum, which is extremely GC-poor (18% on average). Although the selective advantage for this AT-richness is unknown, it seems evident that under such strong constraints the preferred codons have an A or a T at their third position, rather than a G or C as in most other organisms. However, a careful analysis of codon preferences in different genes reveals that there is a group of genes
Outlook
then stabilize and silence damaged regions while repair occurs. 1 Mills, K. et al. (1999) MEC-1 dependent redistribution of the Sir3 silencing protein from telomeres to DNA double strand breaks. Cell 97, 609–620 2 Martin, S. et al. (1999) Relocalisation of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell 97, 621–633
(apparently the highly expressed ones) that have a noticeable preference for Cending codons. Again, it is unlikely that this could be due only to tRNA availability because, in a genome that shows such a strong general AT-composition bias, the tRNA pool size could probably have been adapted as well. This would lend additional credence to the motifdirected preference hypothesis by Antezana and Kreitman1, which proposes that the codon-usage constraints are ultimately determined through the chemistry of nucleic acids, and that different genomes have adapted to different extents to these constraints. 1 Antezana, M.A. and Kreitman, M. (1999) The nonrandom location of synonymous codons suggests that reading frame-independent forces have patterned codon preferences. J. Mol. Evol. 49, 36–43 2 Musto, H. et al. (1999) Synonymous codon choices in the extremely GC-poor genome of Plasmodium falciparum: compositional constraints and translational selection. J. Mol. Evol. 49, 27–35
Diethard Tautz [email protected]
Included in the November issue of Trends in Genetics Genetic approaches to memory storage by M. Mayford and E.R. Kandel Guilt by association: non-coding RNAs, chromosome-specific proteins and dosage compensation in Drosophila by C. Stuckenholz, Y. Kageyame and M.I. Kuroda Singling out Drosophila tendon cells: a dialogue between two distinct cell types by T. Volk Ci: a complex transducer of the hedgehog signal by P. Aza-Blanc and T.B. Kornberg The mahogany mouse mutation reveals further links between pigmentation, obesity and the immune system by I.J. Jackson Genomic imprinting in mammals: an interplay between chromatin and DNA methylation? by R. Feil and S. Khosla Copying out our ABCs: the role of gene redundancy in interpreting genetic hierarchies by R. Martienssen and V. Irish What’s new in the library? What’s new in GenBank? Let PubCrawler tell you by K. Hokamp and K. Wolfe Small introns tend to occur in GC-rich regions in some but not all vertebrates by L.D. Hurst, C.F.A. Brunton and N.G.C. Smith A conserved RNA structure element involved in regulation of bacterial riboflavin synthesis genes by M.S. Gelfand, A.A. Mironov, J. Jomantas, Y.I. Kozlov and D.A. Perumov
TIG October 1999, volume 15, No. 10
395
staining shifts to a diffuse nuclear pattern. In quantitative CHIP, this is accompanied by a decrease in telomere association and a significant increase in binding proximal to DSBs. Remarkably, the introduction of a single DSB using the HO endonuclease can trigger the complete translocation response, implying it is an active process. Here, Ku relocalization is more rapid and transient than Sir relocalization, which per-
sists for several hours. Relocalization requires the RAD9 and MEC1 checkpoint genes, and only occurs during S phase but is reversible as cells move into G2. The picture emerging is that telomeres might be a sink for preassembled NHEJ repair complexes. In response to damage signals, Ku might rapidly scan the chromosome to locate and bind to the DSBs. Recruited Sir proteins could
Codon-preference riddles The genetic code is redundant but different codons are nonetheless used to different extents. Although this is a common observation for many genes, the mystery of how this comes about is intriguing. Optimal codons can help to achieve translational efficiency and accuracy and it is often thought that this reflects differences in the tRNA pool size. However, the riddle then is why there should be such differences in tRNA pool size. Antezana and Kreitman1 now take a completely different look at this by proposing that there are generally preferred duplet and triplet motifs in DNA and/or RNA, and that codon-usage preferences are only a secondary adaptation to these preferred motifs. They test this assumption with an algorithm that searches for such motifs, not only within but also outside of, the reading frames. This analysis reveals that there are, indeed, preferences outside of the frames that match
those found within the frames. Although the overlap is not complete, the authors suggest that there is a complex interplay between preferred di- and trinucleotide motifs that, in combination, dictate the codon preferences. Thus, different t-RNA pool sizes would be a secondary adaptation to these compositional constraints, rather than the driving force. Musto et al.2 have studied a different type of compositional constraint, namely codon usage in the genome of the parasite Plasmodium falciparum, which is extremely GC-poor (18% on average). Although the selective advantage for this AT-richness is unknown, it seems evident that under such strong constraints the preferred codons have an A or a T at their third position, rather than a G or C as in most other organisms. However, a careful analysis of codon preferences in different genes reveals that there is a group of genes
Outlook
then stabilize and silence damaged regions while repair occurs. 1 Mills, K. et al. (1999) MEC-1 dependent redistribution of the Sir3 silencing protein from telomeres to DNA double strand breaks. Cell 97, 609–620 2 Martin, S. et al. (1999) Relocalisation of telomeric Ku and SIR proteins in response to DNA strand breaks in yeast. Cell 97, 621–633
(apparently the highly expressed ones) that have a noticeable preference for Cending codons. Again, it is unlikely that this could be due only to tRNA availability because, in a genome that shows such a strong general AT-composition bias, the tRNA pool size could probably have been adapted as well. This would lend additional credence to the motifdirected preference hypothesis by Antezana and Kreitman1, which proposes that the codon-usage constraints are ultimately determined through the chemistry of nucleic acids, and that different genomes have adapted to different extents to these constraints. 1 Antezana, M.A. and Kreitman, M. (1999) The nonrandom location of synonymous codons suggests that reading frame-independent forces have patterned codon preferences. J. Mol. Evol. 49, 36–43 2 Musto, H. et al. (1999) Synonymous codon choices in the extremely GC-poor genome of Plasmodium falciparum: compositional constraints and translational selection. J. Mol. Evol. 49, 27–35
Diethard Tautz [email protected]
Included in the November issue of Trends in Genetics Genetic approaches to memory storage by M. Mayford and E.R. Kandel Guilt by association: non-coding RNAs, chromosome-specific proteins and dosage compensation in Drosophila by C. Stuckenholz, Y. Kageyame and M.I. Kuroda Singling out Drosophila tendon cells: a dialogue between two distinct cell types by T. Volk Ci: a complex transducer of the hedgehog signal by P. Aza-Blanc and T.B. Kornberg The mahogany mouse mutation reveals further links between pigmentation, obesity and the immune system by I.J. Jackson Genomic imprinting in mammals: an interplay between chromatin and DNA methylation? by R. Feil and S. Khosla Copying out our ABCs: the role of gene redundancy in interpreting genetic hierarchies by R. Martienssen and V. Irish What’s new in the library? What’s new in GenBank? Let PubCrawler tell you by K. Hokamp and K. Wolfe Small introns tend to occur in GC-rich regions in some but not all vertebrates by L.D. Hurst, C.F.A. Brunton and N.G.C. Smith A conserved RNA structure element involved in regulation of bacterial riboflavin synthesis genes by M.S. Gelfand, A.A. Mironov, J. Jomantas, Y.I. Kozlov and D.A. Perumov
TIG October 1999, volume 15, No. 10
395