Relative content of isoaccepting tRNAs for glycine and proline in avian tendon cells with different rates of procollagen synthesis

FoxP2 is the first identified gene that is specifically involved in speech and language development in humans. Population genetic studies of FoxP2 revealed a selective sweep in recent human history associated with two amino acid substitutions in exon 7. Avian song learning and human language acquisition share many behavioral and neurological similarities. To determine whether FoxP2 plays a similar role in song-learning birds, we sequenced exon 7 of FoxP2 in multiple song-learning and nonlearning birds. We show extreme conservation of FoxP2 sequences in birds, including unusually low rates of synonymous substitutions. However, no amino acid substitutions are shared between the song-learning birds and humans. Furthermore, sequences from vocal-learning whales, dolphins, and bats do not share the human-unique substitutions. While FoxP2 appears to be under strong functional constraints in mammals and birds, we find no evidence for its role during the evolution of vocal learning in nonhuman animals as in humans.

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Expression of Human nPTB Is Limited by Extreme Suboptimal Codon Content

Robinson

Jackson

Smith

2008

PLoS ONE

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BackgroundThe frequency of synonymous codon usage varies widely between organisms. Suboptimal codon content limits expression of viral, experimental or therapeutic heterologous proteins due to limiting cognate tRNAs. Codon content is therefore often adjusted to match codon bias of the host organism. Codon content also varies between genes within individual mammalian species. However, little attention has been paid to the consequences of codon content upon translation of host proteins.Methodology/Principal FindingsIn comparing the splicing repressor activities of transfected human PTB and its two tissue-restricted paralogs–nPTB and ROD1–we found that the three proteins were expressed at widely varying levels. nPTB was expressed at 1–3% the level of PTB despite similar levels of mRNA expression and 74% amino acid identity. The low nPTB expression was due to the high proportion of codons with A or U at the third codon position, which are suboptimal in human mRNAs. Optimization of the nPTB codon content, akin to the “humanization” of foreign ORFs, allowed efficient translation in vivo and in vitro to levels comparable with PTB. We were then able to demonstrate that all three proteins act as splicing repressors.Conclusions/SignificanceOur results provide a striking illustration of the importance of mRNA codon content in determining levels of protein expression, even within cells of the natural host species.

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Relative content of isoaccepting tRNAs for glycine and proline in avian tendon cells with different rates of procollagen synthesis

Cited by 3 publications

References 17 publications

Isolation of a mouse genomic clone containing four tRNACys-encoding genes

Isolation of a mouse genomic clone containing four tRNACys-encoding genes

FoxP2 in Song-Learning Birds and Vocal-Learning Mammals

Expression of Human nPTB Is Limited by Extreme Suboptimal Codon Content

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