Departament de Genètica, Facultat de Biologia, Universitat de Barcelona 08028, Barcelona, Spain.
Genome Res. 2012 Apr;22(4):642-55. doi: 10.1101/gr.132233.111. Epub 2012 Jan 10.
Developmental genes are regulated by complex, distantly located cis-regulatory modules (CRMs), often forming genomic regulatory blocks (GRBs) that are conserved among vertebrates and among insects. We have investigated GRBs associated with Iroquois homeobox genes in 39 metazoans. Despite 600 million years of independent evolution, Iroquois genes are linked to ankyrin-repeat-containing Sowah genes in nearly all studied bilaterians. We show that Iroquois-specific CRMs populate the Sowah locus, suggesting that regulatory constraints underlie the maintenance of the Iroquois-Sowah syntenic block. Surprisingly, tetrapod Sowah orthologs are intronless and not associated with Iroquois; however, teleost and elephant shark data demonstrate that this is a derived feature, and that many Iroquois-CRMs were ancestrally located within Sowah introns. Retroposition, gene, and genome duplication have allowed selective elimination of Sowah exons from the Iroquois regulatory landscape while keeping associated CRMs, resulting in large associated gene deserts. These results highlight the importance of CRMs in imposing constraints to genome architecture, even across large phylogenetic distances, and of gene duplication-mediated genetic redundancy to disentangle these constraints, increasing genomic plasticity.
发育基因受复杂的、远距离的顺式调控模块（CRMs）调控，这些模块通常形成在脊椎动物和昆虫中保守的基因组调控块（GRBs）。我们已经在 39 种后生动物中研究了与 Iroquois 同源盒基因相关的 GRBs。尽管经历了 6 亿年的独立进化，Iroquois 基因在几乎所有研究的两侧对称动物中都与 ankryn-repeat-containing Sowah 基因相连。我们表明，Iroquois 特异性 CRM 填充 Sowah 基因座，这表明调节限制是维持 Iroquois-Sowah 同线性块的基础。令人惊讶的是，四足动物 Sowah 同源基因没有内含子，也不与 Iroquois 相关；然而，硬骨鱼和象鲨的数据表明，这是一个衍生特征，许多 Iroquois-CRM 最初位于 Sowah 内含子中。反转录转座、基因和基因组复制允许 Sowah 外显子从 Iroquois 调控景观中选择性消除，同时保留相关的 CRM，导致大的相关基因荒漠。这些结果强调了 CRM 在施加对基因组结构的限制方面的重要性，即使跨越大的系统发育距离，以及基因复制介导的遗传冗余在解开这些限制、增加基因组可塑性方面的重要性。
