Fast-Evolving Human-Specific Neural Enhancers Are Associated with Aging-Related Diseases.

ABSTRACT: The antagonistic pleiotropy theory hypothesizes that evolutionary adaptations maximizing the fitness in early age increase disease burden after reproduction. This theory remains largely untested at the molecular level. Here, we analyzed enhancer evolution in primates to investigate the relationships between aging-related diseases and enhancers acquired after the human-chimpanzee divergence. We report a 5-fold increased evolutionary rate of enhancers that are activated in neural tissues, leading to fixation of ∼100 human-specific enhancers potentially under adaptation. These enhancers show prognostic expression levels and correlations with driver genes in cancer, and their nearby genes are enriched in known loci associated with aging-related diseases. Using CRISPR/Cas9, we further functiona

SUBMITTER: Chen H 

PROVIDER: S-EPMC5972385 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature