Regulatory evolution of innate immunity through co-option of endogenous retroviruses

Abstract

Endogenous retroviruses (ERVs) are abundant in mammalian genomes and contain sequences modulating transcription. How ERV propagation impacts the evolution of gene regulation remains poorly understood. Here we show that ERVs have shaped the evolution of a transcriptional network underlying the interferon (IFN) response, a major branch of innate immunity. We found that lineage-specific ERVs have dispersed numerous IFN-inducible enhancers independently in diverse mammalian genomes. CRISPR-Cas9 deletion of a subset of these ERV elements in the human genome impaired expression of adjacent IFN-induced genes and revealed their involvement in the regulation of essential immune functions, including activation of the AIM2 inflammasome. While these regulatory sequences likely arose in ancient viruses, they now constitute a dynamic reservoir of IFN-inducible enhancers fueling genetic innovation in mammalian immune defenses.

Retracted:HBx‐mediated decrease of AIM2 contributes to hepatocellular carcinoma metastasis

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“…В рамках последней все-таки полученный иммунитет не переводит соответствующие инфекции в статус внутренних позитивных ориентиров для прогрессивного развития форм органической жизни. Правда, в последнее время появляются исследования, доказывающие вирусную природу иммунной системы и некоторых частей ДНК [Chuong, 2016;Brouillette, 2016]. 16 В несколько другом контексте эта идея социальной динамики и культурной диффузии через восприятие чужеродного развивалась Г. Зиммелем в его концепции «Чужака» и независимо от последнего А. Щюцем («the Stranger») [Щюц, 2004: 533-549].…”