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Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation

Lichen Ren1, Ge Gao2, Dongxin Zhao3, Mingxiao Ding3, Jingchu Luo2 and Hongkui Deng3*

Author Affiliations

1 College of Life Sciences, Shanghai Jiao Tong University, Shanghai, 200240, PR China

2 Center for Bioinformatics, College of Life Sciences, National Laboratory of Protein Engineering and Plant Genetics Engineering, Peking University, Beijing, 100871, PR China

3 Department of Cell Biology and Genetics, College of Life Sciences, Peking University, Beijing, 100871, PR China

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Genome Biology 2007, 8:R35  doi:10.1186/gb-2007-8-3-r35

Published: 12 March 2007



The usage of synonymous codons shows considerable variation among mammalian genes. How and why this usage is non-random are fundamental biological questions and remain controversial. It is also important to explore whether mammalian genes that are selectively expressed at different developmental stages bear different molecular features.


In two models of mouse stem cell differentiation, we established correlations between codon usage and the patterns of gene expression. We found that the optimal codons exhibited variation (AT- or GC-ending codons) in different cell types within the developmental hierarchy. We also found that genes that were enriched (developmental-pivotal genes) or specifically expressed (developmental-specific genes) at different developmental stages had different patterns of codon usage and local genomic GC (GCg) content. Moreover, at the same developmental stage, developmental-specific genes generally used more GC-ending codons and had higher GCg content compared with developmental-pivotal genes. Further analyses suggest that the model of translational selection might be consistent with the developmental stage-related patterns of codon usage, especially for the AT-ending optimal codons. In addition, our data show that after human-mouse divergence, the influence of selective constraints is still detectable.


Our findings suggest that developmental stage-related patterns of gene expression are correlated with codon usage (GC3) and GCg content in stem cell hierarchies. Moreover, this paper provides evidence for the influence of natural selection at synonymous sites in the mouse genome and novel clues for linking the molecular features of genes to their patterns of expression during mammalian ontogenesis.