Kuvaeva Elena E, Cherezov Roman O, Kulikova Dina A, Mertsalov Ilya B
Koltzov Institute of Developmental Biology of Russian Academy of Sciences, 26 Vavilov Street, 119334 Moscow, Russia.
Int J Mol Sci. 2024 Dec 13;25(24):13394. doi: 10.3390/ijms252413394.
has two paralogs, and , related to the evolutionarily conserved family genes. In mammals, the family consists of , encoding transcription co-factors involved in the regulation of development and cell fate determination. The function of and in remains unclear. The typical domain structure of the proteins encoded by the family consists of an N-terminal 2/3 domain (Requiem_N), a central Kruppel-type zinc finger, and a C-terminal D4 domain of paired PHD zinc fingers (DPFs). In , both paralogs lack the Kruppel-type ZF, and encodes a protein that contains only Requiem_N. In contrast, vertebrate paralogs encode all the domains, but some paralogs have specific splice isoforms. For example, the DPF3a isoform lacks the D4 domain necessary for histone reading. The occurrence of proteins without the D4 domain in mammals and flies implies functional significance and analogous roles across animal taxa. In this study, we reconstructed the evolutionary events that led to the emergence of by analyzing the divergence of paralogs across different evolutionary lineages. Our genomic and transcriptomic data analysis revealed duplications and gene copy loss events. Among insects, gene duplication was only observed in Diptera. In other lineages, we found the specialization of paralogs for producing isoforms and further specialization for coding proteins with specific domain organizations. We hypothesize that this pathway is a common mechanism for the emergence of paralogues lacking the D4 domain across different evolutionary lineages. We, thus, postulate that TTH may function as a splice isoform of the ancestral single-copy gene, possibly a DPF3a-like isoform characteristic of related insect species. Our analysis provides insights into the possible impact of paralogue divergence, emphasizing the functional significance of the 2/3 domain and the potential roles of isoforms lacking the D4 domain.
有两个旁系同源基因， 和 ，与进化上保守的 家族基因相关。在哺乳动物中，该家族由 组成，其编码参与发育调控和细胞命运决定的转录共因子。 和 在 中的功能仍不清楚。 家族编码的蛋白质的典型结构域结构由一个N端2/3结构域（Requiem_N）、一个中央克鲁佩尔型锌指和一个由成对的PHD锌指（DPFs）组成的C端D4结构域组成。在 中，两个旁系同源基因都缺乏克鲁佩尔型锌指，并且 编码一种仅包含Requiem_N的蛋白质。相比之下，脊椎动物的 旁系同源基因编码所有结构域，但一些旁系同源基因有特定的剪接异构体。例如，DPF3a异构体缺乏组蛋白识别所需的D4结构域。在哺乳动物和果蝇中出现没有D4结构域的蛋白质意味着其在不同动物类群中的功能重要性和类似作用。在本研究中，我们通过分析不同进化谱系中 旁系同源基因的差异，重建了导致 出现的进化事件。我们的基因组和转录组数据分析揭示了重复和基因拷贝丢失事件。在昆虫中，基因重复仅在双翅目中观察到。在其他谱系中，我们发现旁系同源基因在产生异构体方面的特化以及在编码具有特定结构域组织的蛋白质方面的进一步特化。我们假设这条途径是不同进化谱系中缺乏D4结构域的旁系同源基因出现的常见机制。因此，我们推测TTH可能作为祖先单拷贝基因的剪接异构体发挥作用，可能是相关昆虫物种特有的类似DPF3a的异构体。我们的分析为旁系同源基因差异的可能影响提供了见解，强调了2/3结构域的功能重要性以及缺乏D4结构域的异构体的潜在作用。
