title: Developmental stage related patterns of codon usage and genomic GC content: searching for evolutionary fingerprints with models of stem cell differentiation.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: College of Life Sciences, Shanghai Jiao Tong University, Shanghai, PR China. lichen.ren@gmail.com
authors.forename: Lichen
authors.initials: L
authors.lastname: Ren
authors.forename: Ge
authors.initials: G
authors.lastname: Gao
authors.forename: Dongxin
authors.initials: D
authors.lastname: Zhao
authors.forename: Mingxiao
authors.initials: M
authors.lastname: Ding
authors.forename: Jingchu
authors.initials: J
authors.lastname: Luo
authors.forename: Hongkui
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D001482:Base Composition; D005075:Biological Evolution; D002454:Cell Differentiation; D003062:Codon / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D012641:Selection, Genetic; D013234:Stem Cells / Q000166:cytology*
chemical_list: D003062:Codon