Limits...
Could protein tertiary structure influence mammary transgene expression more than tissue specific codon usage?

He Z, Zhao Y, Mei G, Li N, Chen Y - Transgenic Res. (2010)

Bottom Line: Animal mammary glands have been successfully employed to produce therapeutic recombinant human proteins.However, considerable variation in animal mammary transgene expression efficiency has been reported.We now consider whether aspects of codon usage and/or protein tertiary structure underlie this variation in mammary transgene expression.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, 510006, Guangzhou, People's Republic of China.

ABSTRACT
Animal mammary glands have been successfully employed to produce therapeutic recombinant human proteins. However, considerable variation in animal mammary transgene expression efficiency has been reported. We now consider whether aspects of codon usage and/or protein tertiary structure underlie this variation in mammary transgene expression.

Show MeSH

Related in: MedlinePlus

A dendogram reflecting the codon usage of 22 genes selectively expressed in heart (red) and 17 genes selectively expressed in human kidney (black). The pairwise distances underlying this tree reflect the degree to which the genes differ in their codon usage. As this tree demonstrates, heart-specific genes can generally be distinguished from heart-speicific genes purely on the basis of their synonymous codon usage. The observed separation between these two classes of genes would not have occurred by random chance (P < 0.001)
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2902731&req=5

Fig1: A dendogram reflecting the codon usage of 22 genes selectively expressed in heart (red) and 17 genes selectively expressed in human kidney (black). The pairwise distances underlying this tree reflect the degree to which the genes differ in their codon usage. As this tree demonstrates, heart-specific genes can generally be distinguished from heart-speicific genes purely on the basis of their synonymous codon usage. The observed separation between these two classes of genes would not have occurred by random chance (P < 0.001)

Mentions: We have made pair-wise comparisons of codon usage among seven human tissues. When comparing heart to kidney (Fig. 1), virtually all kidney associated genes are clustered in a separate middle clade from the heart associated genes. The observed separation between these two classes of genes would not have occurred by random chance (P < 0.001). The observed clustering is the result of systematic differential codon usage between heart and kidney specific genes. Fig. 1 indicates that we can generally discriminate between heart and kidney expressed genes on the basis of their codon usage alone. Similarly, kidney specific genes can be discriminated from lung and pancreas specific genes (supplementary Fig. 1). However, many pairs of tissue specific gene sets do not exhibit significantly different codon usage patterns (e.g., brain versus pancreas, P = 0.384; supplementary Fig. 2). Unexpectedly, in the tested six mouse tissues, we can not observe any pair of tissues that can be separated from each other on the basis of their codon usage with a statistical significant test. Only heart specific genes can be nearly discriminated from liver specific genes (P = 0.072; supplementary Fig. 3).Fig. 1


Could protein tertiary structure influence mammary transgene expression more than tissue specific codon usage?

He Z, Zhao Y, Mei G, Li N, Chen Y - Transgenic Res. (2010)

A dendogram reflecting the codon usage of 22 genes selectively expressed in heart (red) and 17 genes selectively expressed in human kidney (black). The pairwise distances underlying this tree reflect the degree to which the genes differ in their codon usage. As this tree demonstrates, heart-specific genes can generally be distinguished from heart-speicific genes purely on the basis of their synonymous codon usage. The observed separation between these two classes of genes would not have occurred by random chance (P < 0.001)
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2902731&req=5

Fig1: A dendogram reflecting the codon usage of 22 genes selectively expressed in heart (red) and 17 genes selectively expressed in human kidney (black). The pairwise distances underlying this tree reflect the degree to which the genes differ in their codon usage. As this tree demonstrates, heart-specific genes can generally be distinguished from heart-speicific genes purely on the basis of their synonymous codon usage. The observed separation between these two classes of genes would not have occurred by random chance (P < 0.001)
Mentions: We have made pair-wise comparisons of codon usage among seven human tissues. When comparing heart to kidney (Fig. 1), virtually all kidney associated genes are clustered in a separate middle clade from the heart associated genes. The observed separation between these two classes of genes would not have occurred by random chance (P < 0.001). The observed clustering is the result of systematic differential codon usage between heart and kidney specific genes. Fig. 1 indicates that we can generally discriminate between heart and kidney expressed genes on the basis of their codon usage alone. Similarly, kidney specific genes can be discriminated from lung and pancreas specific genes (supplementary Fig. 1). However, many pairs of tissue specific gene sets do not exhibit significantly different codon usage patterns (e.g., brain versus pancreas, P = 0.384; supplementary Fig. 2). Unexpectedly, in the tested six mouse tissues, we can not observe any pair of tissues that can be separated from each other on the basis of their codon usage with a statistical significant test. Only heart specific genes can be nearly discriminated from liver specific genes (P = 0.072; supplementary Fig. 3).Fig. 1

Bottom Line: Animal mammary glands have been successfully employed to produce therapeutic recombinant human proteins.However, considerable variation in animal mammary transgene expression efficiency has been reported.We now consider whether aspects of codon usage and/or protein tertiary structure underlie this variation in mammary transgene expression.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, 510006, Guangzhou, People's Republic of China.

ABSTRACT
Animal mammary glands have been successfully employed to produce therapeutic recombinant human proteins. However, considerable variation in animal mammary transgene expression efficiency has been reported. We now consider whether aspects of codon usage and/or protein tertiary structure underlie this variation in mammary transgene expression.

Show MeSH
Related in: MedlinePlus