Mackenzie Alasdair, Miller Kerry Ann, Collinson Jon Martin
School of Medical Sciences, University of Aberdeen, Aberdeen, Scotland.
Bioessays. 2004 Nov;26(11):1217-24. doi: 10.1002/bies.20117.
It is often overlooked that, in addition to the integrity of protein-coding sequences (PCSs), human health is crucially linked to the normal expression of genes by cis-regulatory sequences (CRSs). These CRSs often lie at some considerable distance from the PCSs whose expression they control and often within other genes. The resulting gene interdigitation can make long-range CRS identification and characterisation difficult. We propose that the need to conserve long-range CRSs in cis with their target PCSs through evolution, in combination with gene interdigitation and co-regulation of many genes by individual CRSs, has contributed to the persistence of conserved synteny blocks between diverse species. We further hypothesise that examination of the varying extents of synteny blocks between multiple species in combination with phylogenetic footprinting to find CRSs might provide important clues to the existence of crucial functional CRS-PCS linkages. Identifying CRS-PCS linkages crucial to human health will lead to a better understanding of how their disruption by CRS mutation or chromosome translocation might contribute to many distressing human diseases.
人们常常忽视，除了蛋白质编码序列（PCS）的完整性外，人类健康还与顺式调控序列（CRS）对基因的正常表达密切相关。这些CRS通常与它们所控制表达的PCS相距甚远，且常常位于其他基因内部。由此产生的基因相互交错会使远距离CRS的识别和表征变得困难。我们认为，在进化过程中需要顺式保留远距离CRS及其靶标PCS，再加上基因相互交错以及单个CRS对许多基因的共同调控，导致了不同物种之间保守同线性模块的持续存在。我们进一步假设，结合系统发育足迹法来寻找CRS，研究多个物种之间不同程度的同线性模块，可能会为关键功能性CRS-PCS联系的存在提供重要线索。识别对人类健康至关重要的CRS-PCS联系，将有助于更好地理解CRS突变或染色体易位对它们的破坏如何导致许多令人痛苦的人类疾病。
