Transposable Element Domestication As an Adaptation to Evolutionary Conflicts

Abstract

Transposable elements (TEs) are selfish genetic units that typically encode proteins that enable their proliferation in the genome and spread across individual hosts. Here we review a growing number of studies that suggest that TE proteins have often been co-opted or 'domesticated' by their host as adaptations to a variety of evolutionary conflicts. In particular, TE-derived proteins have been recurrently repurposed as part of defense systems that protect prokaryotes and eukaryotes against the proliferation of infectious or invasive agents, including viruses and TEs themselves. We argue that the domestication of TE proteins may often be the only evolutionary path toward the mitigation of the cost incurred by their own selfish activities.

Keywords: adaptation; evolutionary conflicts; transposable element protein domestication.

Key Figure, figure 1

Transposition mechanisms of major types of transposable elements highlighting genes and functions that are involved in conflict. Class I elements or retrotransposons transpose via RNA intermediates (A and B), and Class II elements or DNA transposons mobilize directly as DNA molecules (C). We include retroviruses and endogenous retroviruses under LTR retrotransposons as previously proposed [100]. A. A typical non-LTR retroelement transposition (i.e., LINE element) is initiated by the transcription of the element. The transcript is translated into proteins and they associate with the mRNA and translocate into the nucleus. The retrotranscriptase (RT) protein has endonuclease activity and makes a nick on one of the strands and uses the 3’ end to prime synthesize a cDNA copy and insert into the genome. This process is known as target primed reverse transcription (TPRT). The nicks generated on two DNA strands are generally staggered and this results in target site duplications (TSDs). B. A typical LTR retrotransposon is characterized by long terminal repeats (LTRs) and generally encodes for three major proteins (GAG, POL, and ENV). The transposition is initiated by the transcription of three encoded genes as a single mRNA. The transcript is translated into several protein products. The POL gene is translated to three proteins, integrase (INT), RNAse H (RH), and RT. The GAG forms the capsid protein that encapsulated the LTR mRNA, int, RH, RT into a nucleocapsid virus like particle (VLP). The ENV, which is a glycoprotein, can promote the escape of the VLP from the cell. In the extracellular space, the viral surface ENV glycoprotein can recognize susceptible cells through recognition of the cell receptors and fuse with the cell membrane. Once fused, the nucleocapsid can enter into the cell cytoplasm. Alternatively, the VLP, instead of escaping the cell, can continue the transposition process within a single host cell. In the VLP, the RT reverse transcribes the RNA into cDNA which then associated with the INT. The INT guides the cDNA into the nucleus, where it finds a target site and integrates the element into the genome. Since the INT usually generates a staggered cut, the LTR elements are flanked by TSDs. C. A typical cut and paste DNA TE is flanked by target site duplications (TSDs), Terminal inverted repeats (TIRs) and encodes for at least a transposase. The transposition of the cut and paste element is initiated when the transposase is transcribed and translated. The transposase can either stay as monomer or form multimers. Alternatively, the transposase can also interact with other proteins (either encoded by the TE itself or host proteins). The transposase is then able to translocate into the nucleus where it recognizes and binds the TIRs. After binding to the TIRs the transposase catalyzes the excision of the TE from the donor site. When the TE (bound to the transposase) finds a target site, it makes a staggered cut and inserts itself into the new site. When the staggered cuts are repaired the TE remains flanked by TSDs.

Figure I

Model of the inevitability of TE domestication using ciliates as example. i) A novel TE invades a naïve ciliate genome and expands in copy number. Upon integration, TEs can potentially disrupt genes and regulatory sequences. ii) Because ciliates have dimorphic nuclei, micronucleus (MIC) and macronucleus (MAC), the organisms in which the TEs evolve to precisely excise during the transformation from the MIC to the MAC will have intact coding regions and regulatory sequences and will survive. These TEs will proliferate undetected by the host. Host with mutated copies of the TEs which cannot excise due to mutations in the TIRs or transposases cannot form intact ORF in the MAC and do not survive. Thus there is purifying selection and organisms that harbor TEs able to precisely excise, provided there are enough active TE copies that provide a source of transposase for excision have higher fitness. These TEs will keep proliferating and the potential for deleterious mutations in the TIRs will increase. iii) Conflict between TE and host is resolved by domesticating a TE protein to excise related TEs during the transition to the MAC nucleus. iv) Overtime the TE-related sequences accumulate mutations beyond recognition. However, the regions of TE (generally parts of TIRs) are under purifying selection since these sequences are important for the excision of disruptive sequences and gives rise to IESs.