Mammalian genome innovation through transposon domestication

Abstract

Since the discovery of transposons, their sheer abundance in host genomes has puzzled many. While historically viewed as largely harmless 'parasitic' DNAs during evolution, transposons are not a mere record of ancient genome invasion. Instead, nearly every element of transposon biology has been integrated into host biology. Here we review how host genome sequences introduced by transposon activities provide raw material for genome innovation and document the distinct evolutionary path of each species.

Figure 1.. Transposon domestication contributes to host biology.

Transposon domestication provides new mechanisms for host genome innovation in diverse developmental and physiological processes, generating numerous gene regulatory elements, functional ncRNAs and protein-coding genes^{,,,,,,,,,,,,–,,,,,,,,,,–}. The diagram, while likely representing the tip of an iceberg, summarizes key studies that characterize the in vivo validated transposon functions in the host genomes.

Figure 2.. Transposon-derived gene regulatory elements diversify host gene isoforms and enrich expression regulation modality.

Transposon-derived sequences contribute to gene enhancers, promoters, exons, terminators, splicing donors/acceptors, and chromatin boundaries, regulating the structure and expression of proximal host gene isoforms. TE domestication expands gene regulatory modality, enriches transcript diversity, and diversifies functional reservoirs in host genomes. Pink squares, TE elements; blue squares, protein coding exons or protein coding genes; red hexagons, CTCF; yellow star, a gene regulatory element.

Figure 3.. Transposons confer unique modes of cis-gene regulation in host genomes.

Compared to other gene regulatory sequences, transposons have distinct properties, as they are repetitive in nature and frequently species-specific. Species-specific gene regulation occurs when distinct TEs integrate proximal to homologous genes across species, generating a unique expression pattern in each species (top). Convergent gene regulation occurs when distinct TE insertions across species converge on the same regulatory principal to yield nearly identical expression patterns (middle). Coordinated gene regulation occurs when related transposon elements from the same TE family spread in a given host genome and land proximal to a cohort of host genes to coordinate their expression (bottom).

Figure 4:. Co-option of transposon-encoded proteins contributes to new host biology.

A diagram illustrates the functional parallel between the retroviral Gag, Pol and Env proteins and their domesticated counterparts encoded by retrotransposons. Retroviral life cycle (top) begins when retroviruses infect the host cells and integrate into the host genome. Subsequently, the host machineries drives the expression of viral Gag, Pol and Env, allowing the retrovirus to mature before released from the host cells. Here, we show examples of domesticated Gag and Env genes (bottom), which are repurposed for neuronal functions, host defense, and placenta development. The remarkable modern innovations conferred by retrotransposon encoded proteins can be traced back to their proviral functions.