Molecular Evolution and Protein Structure Variation of Dkk Family

Genes (Basel). 2023 Sep 25;14(10):1863. doi: 10.3390/genes14101863.

Abstract

Dkks have inhibitory effects on the Wnt signaling pathway, which is involved in the development of skin and its appendages and the regulation of hair growth. The nucleotide sequences were compared and analyzed to further investigate the relationship between the structure and function of the Dkk gene family and vertebrate epidermal hair. The analysis of the molecular evolution of the Dkk family revealed that the evolution rate of the genes changed significantly after speciation, with the Aves and Reptilia branches showing accelerated evolution. Additionally, positive selection was observed at specific sites. The tertiary structure of the protein was also predicted. The analysis of the functional divergence of the Dkk family revealed that the functional divergence coefficient of each gene was greater than 0, with most of the functional divergence sites were located in the Cys-2 domain and a few in the Cys-1 domain. This suggests that the amino acid and functional divergence sites may play a role in regulating the binding of the Dkk family to LRP5/6, and thus affect the inhibition of Wnt signaling, leading to different functions of Dkk1, Dkk2, and Dkk4 in the development of skin hair follicles. In addition, the Dkk families of Aves and Reptilia may have undergone adaptive evolution and functional divergence.

Keywords: Dkk gene family; functional divergence; hair follicle; molecular evolution.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Evolution, Molecular
  • Intercellular Signaling Peptides and Proteins* / genetics
  • Wnt Signaling Pathway* / genetics

Substances

  • Intercellular Signaling Peptides and Proteins

Grants and funding

This work was supported by the National Natural Science Foundation of China (32260812, 3211101853) to Jianghong Wu and Jun Yin, and the Inner Mongolia Autonomous Region’s Key Technology Tackling Plan (2021GG0008, 2020GG0069), and the Program for Young Talents of Science and Technology in Universities of Inner Mongolia Autonomous Region (2023NJYT23015), and the Youth Program for Grassland Elite in Inner Mongolia Autonomous Region to Jianghong Wu, and the Doctoral Scientific Research Foundation of Inner Mongolia Minzu University (BS527, BS526) to Jianghong Wu and Sile Hu.