Fig. 4. TE-mediated evolution of MSL complex chromatin entry sites (CES).

Comparison of the two evolutionary timepoints of acquiring chromatin entry sites on XR and the neo-X suggest a three-step model for the TE-mediated wiring of a newly evolved X chromosome into the dosage compensation network followed by erosion of non-functional elements of the TE. The first step, domestication, involves the acquisition of a MRE sequence motif capable of acting as a CES for the MSL complex. The domesticated TE is amplified across the genome and beneficial on a newly formed X chromosome but selected against on autosomal locations. This results in the accumulation of the domesticated TE, along with the MRE motif that it carries, on the X. The amplified MRE motif may initially be suboptimal, as seen with the younger ISX elements on the neo-X, but over time, secondary fine-tuning mutations within each MRE can refine the ability to recruit optimal levels of MSL complex, as seem to have occurred with the older ISXR elements on XR. This is accompanied by erosion of TE sequences that are not required for MSL-binding, eventually degrading the signature of TE involvement for supplying CES.