Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Oct 4;25(19):10696.
doi: 10.3390/ijms251910696.

Codon Bias of the DDR1 Gene and Transcription Factor EHF in Multiple Species

Zhiyong Zhang  1 , Wenxi Li  1 , Ziyang Wang  1 , Shuya Ma  1 , Fangyuan Zheng  1 , Hongyu Liu  1 , Xiaodong Zhang  1 , Yueyun Ding  1 , Zongjun Yin  1 , Xianrui Zheng  1
Affiliations

Codon Bias of the DDR1 Gene and Transcription Factor EHF in Multiple Species

Zhiyong Zhang et al. Int J Mol Sci. .

Abstract

Milk production is an essential economic trait in cattle, and understanding the genetic regulation of this trait can enhance breeding strategies. The discoidin domain receptor 1 (DDR1) gene has been identified as a key candidate gene that influences milk production, and ETS homologous factor (EHF) is recognized as a critical transcription factor that regulates DDR1 expression. Codon usage bias, which affects gene expression and protein function, has not been fully explored in cattle. This study aims to examine the codon usage bias of DDR1 and EHF transcription factors to understand their roles in dairy production traits. Data from 24 species revealed that both DDR1 and EHF predominantly used G/C-ending codons, with the GC3 content averaging 75.49% for DDR1 and 61.72% for EHF. Synonymous codon usage analysis identified high-frequency codons for both DDR1 and EHF, with 17 codons common to both genes. Correlation analysis indicated a negative relationship between the effective number of codons and codon adaptation index for both DDR1 and EHF. Phylogenetic and clustering analyses revealed similar codon usage patterns among closely related species. These findings suggest that EHF plays a crucial role in regulating DDR1 expression, offering new insights into genetically regulating milk production in cattle.

Keywords: DDR1; EHF; cattle; codon usage bias; lactation regulation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Construction of DDR1 gene and EHF phylogenetic trees. (a) Phylogenetic tree constructed based on the CDS sequence of the DDR1 gene. (b) Phylogenetic tree constructed based on the CDS sequence of the EHF TFs.
Figure 2
Figure 2
Hierarchical cluster analysis. (a) Cluster analysis of 59 codon systems in the CDS region of the DDR1 gene among 24 species. (b) Cluster analysis of 59 codon systems in the CDS region of the EHF TFs among 24 species.
Figure 3
Figure 3
Species dimensionality reduction cluster analysis. (a) Construction of species PCA dimensionality reduction cluster analysis based on the RSCU values of the CDS sequence codon of the DDR1 gene. (b) Construction of species PCA dimensionality reduction cluster analysis based on the RSCU values of the CDS sequence codon of the EHF TF.
Figure 4
Figure 4
Correlation analysis of codon metrics (* for p ≤ 0.05; ** for p ≤ 0.01; *** for p ≤ 0.001; **** for p ≤ 0.0001). (a) Correlation analysis of codon metrics based on CDS sequences of DDR1 gene, (b) correlation analysis of codon metrics based on CDS sequences of EHF TFs.
Figure 5
Figure 5
PR2 plot analysis. (a) Third codon preference analysis of the DDR1 gene; (b) third codon preference analysis of the EHF TF. The dotted line represents the theoretical codon base usage frequency under mutation pressure, where A/T and C/G would be used at equal frequencies. The dots indicate the actual codon usage frequencies, reflecting the combined influences of both mutation pressure and natural selection.
Figure 6
Figure 6
Multidimensional clustering analysis of CAI for DDR1–EHF based on k-means.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Do D.N., Dudemaine P.L., Li R., Ibeagha-Awemu E.M. Co-Expression Network and Pathway Analyses Reveal Important Modules of miRNAs Regulating Milk Yield and Component Traits. Int. J. Mol. Sci. 2017;18:1560. doi: 10.3390/ijms18071560. - DOI - PMC - PubMed
    1. Barker K.T., Martindale J.E., Mitchell P.J., Kamalati T., Page M.J., Phippard D.J., Dale T.C., Gusterson B.A., Crompton M.R. Expression patterns of the novel receptor-like tyrosine kinase, DDR, in human breast tumours. Oncogene. 1995;10:569–575. - PubMed
    1. Faraci-Orf E., McFadden C., Vogel W.F. DDR1 signaling is essential to sustain Stat5 function during lactogenesis. J. Cell. Biochem. 2006;97:109–121. doi: 10.1002/jcb.20618. - DOI - PubMed
    1. Rauner G., Jin D.X., Miller D.H., Gierahn T.M., Li C.M., Sokol E.S., Feng Y.X., Mathis R.A., Love J.C., Gupta P.B., et al. Breast tissue regeneration is driven by cell-matrix interactions coordinating multi-lineage stem cell differentiation through DDR1. Nat. Commun. 2021;12:7116. doi: 10.1038/s41467-021-27401-6. - DOI - PMC - PubMed
    1. Zhang X., Hu Y., Pan Y., Xiong Y., Zhang Y., Han M., Dong K., Song J., Liang H., Ding Z., et al. DDR1 promotes hepatocellular carcinoma metastasis through recruiting PSD4 to ARF6. Oncogene. 2022;41:1821–1834. doi: 10.1038/s41388-022-02212-1. - DOI - PMC - PubMed

LinkOut - more resources