The coevolution between APOBEC3 and retrotransposons in primates

Abstract

Retrotransposons are genetic elements with the ability to replicate in the genome using reverse transcriptase: they have been associated with the development of different biological structures, such as the Central Nervous System (CNS), and their high mutagenic potential has been linked to various diseases, including cancer and neurological disorders. Throughout evolution and over time, Primates and Homo had to cope with infections from viruses and bacteria, and also with endogenous retroelements. Therefore, host genomes have evolved numerous methods to counteract the activity of endogenous and exogenous pathogens, and the APOBEC3 family of mutators is a prime example of a defensive mechanism in this context.In most Primates, there are seven members of the APOBEC3 family of deaminase proteins: among their functions, there is the ability to inhibit the mobilization of retrotransposons and the functionality of viruses. The evolution of the APOBEC3 proteins found in Primates is correlated with the expansion of two major families of retrotransposons, i.e. ERV and LINE-1.In this review, we will discuss how the rapid expansion of the APOBEC3 family is linked to the evolution of retrotransposons, highlighting the strong evolutionary arms race that characterized the history of APOBEC3s and endogenous retroelements in Primates. Moreover, the possible role of this relationship will be assessed in the context of embryonic development and brain-associated diseases.

The Intricate Interplay between APOBEC3 Proteins and DNA Tumour Viruses

“…In addition, evolutionary analyses of APOBEC3 proteins indicate that they have been under strong selective pressure over the last 30 million years. Additionally, polymorphisms have been found that contribute significantly to their antiviral efficacy [ 45 , 46 , 47 ].…”

“…Traces of APOBEC mutations have been identified in the genomes of vertebrates, implying that APOBECs were important players in the restriction of retroelements and influenced their evolution [ 15 , 45 , 49 ]. Similar to the editing-independent inhibition of viral replication [ 50 ], the restriction of retrotransposition could also be editing-independent [ 14 , 46 , 49 , 51 , 52 ].…”

The Purpose of Adrenarche Is Tumor Suppression: Identification of a Novel, Human-Specific, Kill-Switch Tumor Suppression Mechanism Dependent upon the Dramatic Adrenarchal Rise of Adrenal Androgens

“…And in reference to immune strategies to treat cancer, activation of LINE1 transcription has been shown to be a major mechanism of T cell exhaustion [89]. In response to transposon infection, particularly that of LINE1, primates also underwent a rapid expansion of the APOBEC3 family of cytosine deaminases which degrade transposons by inducing mutations in them [90]. Yet another mechanism of transposon suppression involves a family of zinc finger proteins that bind as transcription factors to methylated CpGs and play a critical role in gene regulation.…”