The evolution of alternative splicing exons in vascular endothelial growth factor A

The C-terminus alternative splicing in VEGFA (vascular endothelial growth factor A) is known for its impact on physiological and pathological angiogenesis. Based on our prediction and RT-PCR verification, we identified anti-angiogenic VEGFA165b isoforms in mouse and rabbit for the first time. We also found that the relative expression level of VEGFA165b isoform had been increasing from rodents to human, and exon8b may have experienced a minor-to-major form exon conversion, possibly correlated with its gain-of-function. It is suggested that introduction of alternative splicing exons (esp. exon6 and exon8b) made important contributions to the transcriptional diversity of VEGFA and played a crucial role in the evolution of its regulatory mechanism.