SRA

The emergence of the vertebrate liver is a prime example of the evolution of complex organs, yet the driving factors behind it remain unknown. Here, we utilize in vivo and in vitro experiments, single-cell transcriptomic data, and gene knockout experiments in mice to probe the evolutionary process of liver. We found that the amphioxus hepatic caecum, an evolutionary progenitor of the vertebrate liver, has only basic metabolic and immune functions, whereas the vertebrate liver appears to have diverse new functions. We discovered that the emergence of new genes from two rounds of whole-genome duplications (2R-WGD) significantly contributes to liver functional complexity in vertebrates. In particular, two new genes from 2R-WGD, kdr and flt4, play a significant role in the development of liver sinusoidal endothelial cells. Additionally, we found that liver-related functions such as coagulation and bile production evolved in a step-by-step manner, with new genes from 2R-WGD playing a significant role. Furthermore, the transfer of heme detoxification from the liver to the spleen during vertebrate evolution was also noted. Together, these findings challenge the common hypothesis that organ evolution is primarily driven by changes in gene regulation, underscoring the importance of new genes in the emergence and diversification of complex organ functions.