Karageorgiou Charikleia, Ruhl Stefan, Gokcumen Omer
Department of Biological Sciences, University at Buffalo, Buffalo, NY, USA.
Department of Oral Biology, School of Dental Medicine, University at Buffalo, Buffalo, NY, USA.
bioRxiv. 2025 Aug 15:2025.08.14.670395. doi: 10.1101/2025.08.14.670395.
Structurally complex regions of the genome are increasingly recognized as engines of evolutionary convergence due to their propensity to generate recurrent gene duplications that give rise to similar gene expression patterns and traits across lineages. However the mutational mechanisms driving these duplications and the regulatory changes enabling novel expression patterns remain poorly understood. The primate amylase locus, marked by independent gene duplications, provides an ideal model to investigate these dynamics. Leveraging high-quality genome assemblies from 53 primates and multi-tissue transcriptomes from Old World monkeys, we reconstructed the evolutionary history of the recurrent gene duplications across the primate phylogeny. Our data suggest that lineage-specific LTR retrotransposon insertions are associated with initial structural instability, while subsequent duplications are primarily driven by non-allelic homologous recombination. Recurrent independent duplications in rhesus macaques, olive baboons, and great apes gave rise to distinct amylase gene copies with convergent expression in the pancreas and salivary glands. We found that these independent gene duplications are accompanied by episodic diversifying selection on lineage-specific copies, likely driving the emergence of functional divergence. Our comparative analyses in primates indicate that the gene ancestral to great ape and was expressed in both salivary glands and pancreas in the Catarrhini ancestor. The great ape-specific duplication of this ancestral gene likely facilitated subfunctionalization into salivary gland- and pancreas-specific expression, respectively. Comparative analysis of primate amylase promoter regions reveals regulatory rewiring, driven by motif turnover mediated by structural rearrangements, and partially explaining evolutionary shifts in expression. Together, our findings highlight how structural and regulatory modularity in complex genomic regions drives evolutionary innovation and molecular convergence, and we provide a genomic framework for dissecting these processes across diverse lineages.
基因组中结构复杂的区域越来越被认为是进化趋同的引擎，因为它们倾向于产生反复出现的基因复制，从而在不同谱系中产生相似的基因表达模式和性状。然而，驱动这些复制的突变机制以及促成新表达模式的调控变化仍知之甚少。以独立基因复制为特征的灵长类动物淀粉酶基因座，为研究这些动态变化提供了一个理想模型。利用来自53种灵长类动物的高质量基因组组装和旧世界猴的多组织转录组，我们重建了整个灵长类系统发育中反复出现的基因复制的进化历史。我们的数据表明，谱系特异性LTR逆转录转座子插入与初始结构不稳定性相关，而随后的复制主要由非等位基因同源重组驱动。恒河猴、东非狒狒和大猩猩中反复出现的独立复制产生了不同的淀粉酶基因拷贝，在胰腺和唾液腺中具有趋同表达。我们发现，这些独立的基因复制伴随着对谱系特异性拷贝的间歇性多样化选择，这可能推动了功能分化的出现。我们在灵长类动物中的比较分析表明，大猩猩和 的祖先基因在狭鼻猴祖先的唾液腺和胰腺中均有表达。这个祖先基因在大猩猩中的特异性复制可能分别促进了向唾液腺和胰腺特异性表达的亚功能化。对灵长类动物淀粉酶启动子区域的比较分析揭示了由结构重排介导的基序更替驱动的调控重排，部分解释了表达的进化变化。总之，我们的研究结果突出了复杂基因组区域中的结构和调控模块性如何驱动进化创新和分子趋同，并且我们提供了一个基因组框架来剖析不同谱系中的这些过程。
