Abstract Even though gene duplication is a key source of new genes and evolutionary innovation, it is unclear how duplicates survive the period immediately following gene duplication, in which both copies are functionally redundant. In the absence of epigenetic silencing, the abundance of the gene product would double after gene duplication, which would often have deleterious effects. However, recent duplicates exhibit low expression levels, which could be at least partially explained by high levels of promoter methylation. What evolutionary paths lead to duplicate hypermethylation, and does it affect both duplicates, or only one? Here, we compare levels of promoter methylation in 10 human and 16 mouse tissues, between singletons and duplicates and among human-mouse orthologs of different kinds (one-to-one, one-to-many, many-to-one, and many-to-many). Our results indicate that: (1) on average, duplicates are more methylated than singletons in mouse, but less methylated than singletons in human, (2) recently duplicated genes tend to exhibit high levels of promoter methylation, (3) genes that undergo duplication tend to be highly methylated before duplication, (4) after gene duplication, one of the copies (the daughter copy, i.e. the one that relocates to a new genomic context) tends to undergo an additional increase in promoter methylation, whereas the other (the parental copy, which remains in the original genomic location) tends to retain pre-duplication methylation levels, and (5) daughter copies tend to be lowly expressed. These observations support a model in which daughter copies are repressed via promoter hypermethylation and can thus survive the filter of purifying selection until both copies diverge functionally.

Mercedes de la Fuente

Isabel Mendizabal

Mira Han

Soojin V Yi

David Alvarez-Ponce

Molecular Biology and Evolution

MOLECULAR BIOLOGY AND EVOLUTION 在分子（包括基因组学）和进化生物学的界面发表研究。我们考虑包含人口、分类、功能和表型组织各个层次的模式、过程和预测的手稿。除了具有更广泛范围和影响的基本发现外，我们还对出版新的和改进的方法、资源、技术和理论感兴趣，这些方法、资源、技术和理论将显着推进进化研究。我们还发表了对基因组进化最新发展的平衡评论和前瞻性观点，提出了分子进化领域或应用的未来方向。

The journal "Molecular Biology and Evolution" focuses on the interface of molecular biology and evolutionary biology, publishing research in this area. We welcome manuscripts that address patterns, processes, and predictions across various levels, including population, taxonomy, function, and phenotype. In addition to fundamental findings with broad implications, we are also interested in publishing new and improved methods, resources, technologies, and theories that significantly advance evolutionary research. Furthermore, we publish balanced reviews and forward-looking perspectives on the latest developments in genome evolution, proposing future directions for the field of molecular evolution and its applications.

《Molecular Biology and Evolution》期刊专注于分子生物学与进化生物学的交叉领域，发表相关研究成果。我们欢迎涉及种群、分类、功能和表型等多个层面的模式、过程和预测的手稿。除了具有广泛影响的基础研究发现外，我们也对新的和改进的方法、资源、技术和理论感兴趣，这些内容将显著推动进化研究的发展。此外，我们还发表关于基因组进化最新进展的综合评论和前瞻性观点，探讨分子进化领域及其应用的未来方向。

Asymmetrical evolution of promoter methylation of mammalian genes after duplication

On average, duplicates are more methylated than singletons in mouse, but less methylated than singletons in human, and observations support a model in which daughter copies are repressed via promoter hypermethylation and can thus survive the filter of purifying selection until both copies diverge functionally.

Category	Quartile
生物学	1
生物学, 遗传学	1
生物学, 生化与分子生物学	2
生物学, 进化生物学	2

Asymmetrical evolution of promoter methylation of mammalian genes after duplication

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Category	Quartile
GENETICS & HEREDITY	1