A molecular systematic evaluation of the squid genus Illex (Cephalopoda: Ommastrephidae) in the North Atlantic Ocean and Mediterranean Sea.
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Animals↗
Biomedical subjects
David B Carlini
Publications and source records attributed to David B Carlini.
Synonymous SNPs provide evidence for selective constraint on human exonic splicing enhancers.
The human SNP database was used to detect selection on 238 hexamers previously identified as exonic splicing enhancers (ESEs). We compared the distribution of the 238 putative ESEs in biallelic and triallelic SNPs within five different functional categories of the SNP database: synonymous, nonsynonymous, introns, UTRs, and nongenic SNPs. Since true ESEs do not function outside of exons, SNPs that disrupt ESE motifs were expected to be more common in nonexonic portions of the genome. Our results supported this expectation: ESEs were least prevalent within synonymous SNPs and most common in nongenic SNPs. There were approximately 11% fewer ESEs within synonymous biallelic SNPs than expected under no selective constraint. We also compared the frequency of neutral SNPs, those where neither allele was an ESE, with deleterious SNPs, those where one or more alleles was an ESE, across the five different functional classes of SNPs. In comparison with the other functional classes of SNPs, synonymous SNPs contained an excess of neutral variants (+1.64% and +6.04% for biallelic and triallelic SNPs, respectively) and a dearth of deleterious variants (-13.11% and -52.39% for biallelic and triallelic SNPs, respectively). The observed patterns were consistent with purifying selection on the 238 hexamers to maintain their function as ESEs. However, in contrast to previous work, we did not find evidence for selection to maintain ESE function at nonsynonymous SNPs because selection at the protein level probably obscured any difference at the level of ESE function.
Alternative Splicing↗
Context-dependent codon bias and messenger RNA longevity in the yeast transcriptome.
Context-dependent codon bias and its relationship with messenger RNA (mRNA) longevity was examined in 4,648 mRNA transcripts of the Saccharomyces cerevisiae transcriptome for which mRNA half-lives have been empirically determined. Surprisingly, rare codon usage (codons used <13 times per 1,000 codons in the genome) increased with mRNA half-life. However, it is shown that this pattern was not due to preference for rare codon use within codon families containing both rare and nonrare codons. Rather, the pattern was due to an increase in the frequency of amino acids encoded solely by rare codons, and a decrease in the frequency of amino acids never encoded by rare codons, with mRNA half-life. When standardized by open reading frame length, the use of consecutive rare codons was also positively correlated with mRNA half-life. There was negative correlation between the usage of synonymous A|T dinucleotides spanning codon boundaries and mRNA half-life, despite the fact that the frequency of AT dinucleotide usage overall, and AT dinucleotide usage at other codon position contexts (e.g., 1-2, 2-3, or 3|1 total), was not correlated with mRNA half-life. The use of A|T dinucleotides at synonymous dicodon boundaries could potentially allow for more efficient 3'-5' degradation by endonucleolytic cleavage.
Codon↗
Experimental reduction of codon bias in the Drosophila alcohol dehydrogenase gene results in decreased ethanol tolerance of adult flies.
The ethanol tolerance of adult transgenic flies of Drosophila containing between zero and ten unpreferred synonymous mutations that reduced codon bias in the alcohol dehydrogenase (Adh) gene was assayed. As the amino acid sequences of the ADH protein were identical in the four genotypes assayed, differences in ethanol tolerance were due to differences in the abundance of ADH protein, presumably driven by the effects of codon bias on translational efficiency. The ethanol tolerance of genotypes decreased with the number of unpreferred synonymous mutations, and a positive correlation between ADH protein abundance and ethanol tolerance was observed. This work confirms that the fitness effects of unpreferred synonymous mutations that reduce codon bias in a highly expressed gene are experimentally measurable in Drosophila melanogaster.
Alcohol Dehydrogenase↗
In vivo introduction of unpreferred synonymous codons into the Drosophila Adh gene results in reduced levels of ADH protein.
The evolution of codon bias, the unequal usage of synonymous codons, is thought to be due to natural selection for the use of preferred codons that match the most abundant species of isoaccepting tRNA, resulting in increased translational efficiency and accuracy. We examined this hypothesis by introducing 1, 6, and 10 unpreferred codons into the Drosophila alcohol dehydrogenase gene (Adh). We observed a significant decrease in ADH protein production with number of unpreferred codons, confirming the importance of natural selection as a mechanism leading to codon bias. We then used this empirical relationship to estimate the selection coefficient (s) against unpreferred synonymous mutations and found the value (s >or= 10(-5)) to be approximately one order of magnitude greater than previous estimates from population genetics theory. The observed differences in protein production appear to be too large to be consistent with current estimates of the strength of selection on synonymous sites in D. melanogaster.
Alcohol Dehydrogenase↗