Analysis of candidate genes for lineage-specific expression changes in humans and primates

Area of Science:

• Evolutionary biology
• Genomics
• Proteomics

Background:

• RUNX2 (Runt-related transcription factor 2) is crucial for skeletal development and may have undergone positive selection in human evolution.
• Understanding evolutionary changes in RUNX2 interacting partners provides insights into human adaptation.

Purpose of the Study:

• To investigate differences in the expression patterns of RUNX2 interacting proteins across primate evolution.
• To identify specific RUNX2 partners with altered expression between humans and macaques.

Main Methods:

• Antibody-based proteomics and immunohistochemistry were used to profile 50 RUNX2 partners in human and macaque tissue microarrays.
• Protein expression data were compared with RNA sequencing data and analyzed for genomic features in multiple primate species.

Main Results:

• Eleven RUNX2 interacting proteins exhibited differential expression between humans and macaques.
• The gene TCF3 showed significant protein and RNA expression differences, with higher levels in human germ cells compared to macaques.

Conclusions:

• Expression variations in RUNX2 partners were identified in normal tissues between humans and macaques, localizing to specific cell types.
• This proteomic strategy effectively characterizes functional consequences of genes under evolutionary selection.