Department of Genetics, Environment and Evolution, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK.
BMC Evol Biol. 2012 Jan 14;12:5. doi: 10.1186/1471-2148-12-5.
Sex determining mechanisms are evolutionarily labile and related species often use different primary signals and gene regulatory networks. This is well illustrated by the sex determining cascade of Drosophila fruitflies, which have recruited Sex-lethal as the master switch and cellular memory of sexual identity, a role performed in other insects by the gene transformer. Here we investigate the evolutionary change in the coding sequences of sex determining genes associated with the recruitment of Sex-lethal. We analyze sequences of Sex-lethal itself, its Drosophila paralogue sister-or-Sex-lethal and downstream targets transformer and doublesex.
We find that the recruitment of sister-or-Sex-lethal was associated with a number of adaptive amino acid substitutions, followed by a tightening of purifying selection within the Drosophila clade. Sequences of the paralogue sister-or-Sex-lethal, in contrast, show a signature of rampant positive selection and relaxation of purifying selection. The recruitment of Sex-lethal as top regulator and memory gene is associated with a significant release from purifying selection in transformer throughout the Drosophila clade. In addition, doublesex shows a signature of positive selection and relaxation of purifying selection in the Drosophila clade. A similar pattern is seen in sequences from the sister Tephritidae clade.
The pattern of molecular evolution we observe for Sex-lethal and its paralogue sister-or-Sex-lethal is not characteristic of a duplication followed by neo-functionalization. Rather, evidence suggests a sub-functionalization scenario achieved through the evolution of sophisticated splicing. As expected, we find that transformer evolves under relaxed purifying selection after the recruitment of Sex-lethal in Drosophila. Finally, the observation of doublesex adaptation in both Drosophila and Tephritidae suggests that these changes are due to ongoing adaptation of downstream sex-specific regulation, rather than being associated the recruitment of Sex-lethal and the resulting change in the topology of the sex determining cascade.
性别决定机制在进化上是不稳定的，相关物种通常使用不同的主要信号和基因调控网络。这在果蝇的性别决定级联中得到了很好的说明，果蝇已经招募了 Sex-lethal 作为主开关和性身份的细胞记忆，而在其他昆虫中，这个角色是由基因 transformer 来执行的。在这里，我们研究了与 Sex-lethal 招募相关的性别决定基因的编码序列的进化变化。我们分析了 Sex-lethal 本身、其果蝇同源物 sister-or-Sex-lethal 以及下游靶标 transformer 和 doublesex 的序列。
我们发现，sister-or-Sex-lethal 的招募与许多适应性氨基酸取代有关，随后在果蝇分支内纯化选择的紧密度增加。相比之下，sister-or-Sex-lethal 的序列显示出猖獗的正选择和纯化选择放松的特征。Sex-lethal 作为顶级调节剂和记忆基因的招募与整个果蝇分支中 transformer 中的纯化选择显著释放有关。此外，doublesex 在果蝇分支中显示出正选择和纯化选择放松的特征。在姐妹科的序列中也可以看到类似的模式。
我们观察到 Sex-lethal 和其同源物 sister-or-Sex-lethal 的分子进化模式不符合复制后新功能化的特征。相反，证据表明通过复杂的剪接进化实现了亚功能化。正如预期的那样，我们发现，在果蝇中 Sex-lethal 被招募后，transformer 在进化过程中受到了放松的纯化选择。最后，在果蝇和姐妹科中都观察到 doublesex 的适应，这表明这些变化是由于下游性别特异性调节的持续适应，而不是与 Sex-lethal 的招募和性别决定级联拓扑结构的变化有关。
