Rodríguez-Trelles Francisco, Tarrío Rosa, Ayala Francisco J
Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697-2525, USA.
Int J Dev Biol. 2003;47(7-8):665-73.
Efforts to understand the genetic basis of evolutionary change have concentrated on proteins and their encoding DNA sequences. These studies have brought to light patterns and processes at the nucleotide level, yet the complex functional relationships between genetic variants and phenotypes remain poorly known. The realization that even a complete description of proteins and the effects of their activity will not suffice to understand the conditions under which they are time- and tissue-specifically expressed or repressed during development has refocused attention on cis-regulatory regions. In particular, promoter sequences are thought to hold the key for understanding the evolution of phenotypic differences between species. This is because of their complex organization into independent modules such that, unlike coding sequences in which mutations affect protein function every time the protein is expressed, mutations in cis-regulatory sequences may have minor or no pleiotropic effects. Complex information-encoding makes cis-regulatory regions poorly amenable to comparative methods designed for coding sequences. Some general conclusions are emerging as to how genetic variation is distributed across regulatory networks and the processes modulating the structure of this variation. We bring into this emerging scenario several recent findings pointing to different ways in which spliceosomal introns, pseudogenes and patterns of point mutation can be active players for the evolution of novel transcriptional profiles.
理解进化变化的遗传基础的努力主要集中在蛋白质及其编码的DNA序列上。这些研究揭示了核苷酸水平上的模式和过程，然而遗传变异与表型之间复杂的功能关系仍然鲜为人知。人们意识到，即使对蛋白质及其活性效应进行完整描述，也不足以理解它们在发育过程中何时以及在何种组织中特异性表达或被抑制的情况，这使得注意力重新聚焦于顺式调控区域。特别是，启动子序列被认为是理解物种间表型差异进化的关键。这是因为它们的组织形式复杂，形成了独立的模块，与编码序列不同，编码序列中的突变每次蛋白质表达时都会影响蛋白质功能，而顺式调控序列中的突变可能只有轻微的多效性影响或没有多效性影响。复杂的信息编码使得顺式调控区域很难用针对编码序列设计的比较方法进行研究。关于遗传变异如何在调控网络中分布以及调节这种变异结构的过程，一些一般性结论正在浮现。我们将一些近期的研究结果引入到这个新出现的情境中，这些结果指出了剪接体内含子、假基因和点突变模式可以以不同方式成为新转录谱进化的积极参与者。
