High Fitness Costs and Instability of Gene Duplications Reduce Rates of Evolution of New Genes by Duplication-Divergence Mechanisms
High Fitness Costs and Instability of Gene Duplications Reduce Rates of Evolution of New Genes by Duplication-Divergence Mechanisms
复制标题
DOI：
10.1093/molbev/msu111
复制
发表时间：
2014-06-01
影响因子：
10.7
通讯作者：
Sandegren, Linus
中科院分区：
文献类型：
--
作者：
Adler, Marlen;Anjum, Mehreen;Sandegren, Linus
产生新基因的一个重要机制是现有基因的复制-趋异。复制发散包括几个不同的子模型，如亚功能化，其中中性突变的积累后，原始功能分布在两个部分功能和互补基因之间，以及新功能化，其中一个复制副本中的新功能进化，而另一个副本中的旧功能保持不变。这些机制的可能性取决于复制状态的寿命，这反过来又取决于复制的适应性成本和遗传稳定性。在这里，我们确定了低拷贝数质粒上定义的基因重复/扩增的适应性成本和稳定性。我们的实验结果表明，携带额外的基因拷贝的成本是巨大的，每增加一千个碱基对的DNA减少约0.15%的健身。此外，基因扩增是高度不稳定的，并且在不存在选择的情况下快速分离至较低拷贝数。数学建模表明，适应度成本和不稳定性大大降低了子功能化和新功能化的可能性，但这些影响可以通过积极选择新的有益功能来抵消。
An important mechanism for generation of new genes is by duplication-divergence of existing genes. Duplication-divergence includes several different submodels, such as subfunctionalization where after accumulation of neutral mutations the original function is distributed between two partially functional and complementary genes, and neofunctionalization where a new function evolves in one of the duplicated copies while the old function is maintained in another copy. The likelihood of these mechanisms depends on the longevity of the duplicated state, which in turn depends on the fitness cost and genetic stability of the duplications. Here, we determined the fitness cost and stability of defined gene duplications/amplifications on a low copy number plasmid. Our experimental results show that the costs of carrying extra gene copies are substantial and that each additional kilo base pairs of DNA reduces fitness by approximately 0.15%. Furthermore, gene amplifications are highly unstable and rapidly segregate to lower copy numbers in absence of selection. Mathematical modeling shows that the fitness costs and instability strongly reduces the likelihood of both sub- and neofunctionalization, but that these effects can be offset by positive selection for novel beneficial functions.