Umeå Center for Molecular Medicine, Umeå University, 901-87 Umeå, Sweden.
Sci Rep. 2017 Feb 27;7:42029. doi: 10.1038/srep42029.
Understanding the loss of conserved genes is critical for determining how phenotypic diversity is generated. Here we focus on the evolution of DCC, a gene that encodes a highly conserved neural guidance receptor. Disruption of DCC in animal models and humans results in major neurodevelopmental defects including commissural axon defects. Here we examine DCC evolution in birds, which is of particular interest as a major model system in neurodevelopmental research. We found the DCC containing locus was disrupted several times during evolution, resulting in both gene losses and faster evolution rate of salvaged genes. These data suggest that DCC had been lost independently twice during bird evolution, including in chicken and zebra finch, whereas it was preserved in many other closely related bird species, including ducks. Strikingly, we observed that commissural axon trajectory appeared similar regardless of whether DCC could be detected or not. We conclude that the DCC locus is susceptible to genomic instability leading to independent disruptions in different branches of birds and a significant influence on evolution rate. Overall, the phenomenon of loss or molecular evolution of a highly conserved gene without apparent phenotype change is of conceptual importance for understanding molecular evolution of key biological processes.
了解保守基因的丢失对于确定表型多样性是如何产生的至关重要。在这里，我们专注于 DCC 基因的进化，该基因编码一种高度保守的神经导向受体。在动物模型和人类中 DCC 的破坏导致主要的神经发育缺陷，包括连合轴突缺陷。在这里，我们研究了鸟类中的 DCC 进化，这在神经发育研究中是一个特别有趣的主要模型系统。我们发现 DCC 包含的基因座在进化过程中多次被破坏，导致基因丢失和回收基因的进化速度加快。这些数据表明，DCC 在鸟类进化过程中独立丢失了两次，包括鸡和斑马雀，而在许多其他密切相关的鸟类物种中则得到了保留，包括鸭子。值得注意的是，我们观察到连合轴突轨迹似乎相似，无论是否能检测到 DCC。我们得出的结论是，DCC 基因座容易受到基因组不稳定性的影响，导致鸟类不同分支的独立破坏，并对进化速度产生重大影响。总的来说，高度保守基因的缺失或分子进化而没有明显表型变化的现象对于理解关键生物过程的分子进化具有概念上的重要性。
