Shaanxi Key Laboratory of Qinling Ecological Intelligent Monitoring and Protection, School of Ecology and Environment, Northwestern Polytechnical University, Xi'an, China.
Guangdong Key Laboratory of Animal Conservation and Resource Utilization, Institute of Zoology, Guangdong Academy of Sciences, Guangzhou, China.
Nat Ecol Evol. 2024 Oct;8(10):1972-1990. doi: 10.1038/s41559-024-02510-9. Epub 2024 Aug 16.
The evolution of the vertebrate liver is a prime example of the evolution of complex organs, yet the driving genetic factors behind it remain unknown. Here we study the evolutionary genetics of liver by comparing the amphioxus hepatic caecum and the vertebrate liver, as well as examining the functional transition within vertebrates. Using in vivo and in vitro experiments, single-cell/nucleus RNA-seq data and gene knockout experiments, we confirm that the amphioxus hepatic caecum and vertebrate liver are homologous organs and show that the emergence of ohnologues from two rounds of whole-genome duplications greatly contributed to the functional complexity of the vertebrate liver. Two ohnologues, kdr and flt4, play an important role in the development of liver sinusoidal endothelial cells. In addition, we found that liver-related functions such as coagulation and bile production evolved in a step-by-step manner, with gene duplicates playing a crucial role. We reconstructed the genetic footprint of the transfer of haem detoxification from the liver to the spleen during vertebrate evolution. Together, these findings challenge the previous hypothesis that organ evolution is primarily driven by regulatory elements, underscoring the importance of gene duplicates in the emergence and diversification of a complex organ.
脊椎动物肝脏的进化是复杂器官进化的一个典型例子，但背后的驱动遗传因素仍不清楚。在这里，我们通过比较文昌鱼的肝盲囊和脊椎动物的肝脏，以及研究脊椎动物内部的功能转变，来研究肝脏的进化遗传学。我们利用体内和体外实验、单细胞/核 RNA-seq 数据和基因敲除实验，证实了文昌鱼的肝盲囊和脊椎动物的肝脏是同源器官，并表明两轮全基因组复制产生的同源基因对脊椎动物肝脏的功能复杂性有很大的贡献。两个同源基因 kdr 和 flt4 在肝窦内皮细胞的发育中发挥了重要作用。此外，我们发现凝血和胆汁生成等与肝脏相关的功能是逐步进化的，基因重复在其中起着关键作用。我们重建了在脊椎动物进化过程中，血液解毒功能从肝脏转移到脾脏的遗传足迹。总之，这些发现挑战了之前认为器官进化主要由调控元件驱动的假说，强调了基因重复在复杂器官的出现和多样化中的重要性。
