The evolutionary history of human DNA transposons: evidence for intense activity in the primate lineage

Abstract

Class 2, or DNA transposons, make up approximately 3% of the human genome, yet the evolutionary history of these elements has been largely overlooked and remains poorly understood. Here we carried out the first comprehensive analysis of the activity of human DNA transposons over the course of primate evolution using three independent computational methods. First, we conducted an exhaustive search for human DNA transposons nested within L1 and Alu elements known to be primate specific. Second, we assessed the presence/absence of 794 human DNA transposons at orthologous positions in 10 mammalian species using sequence data generated by The ENCODE Project. These two approaches, which do not rely upon sequence divergence, allowed us to classify DNA transposons into three different categories: anthropoid specific (40-63 My), primate specific (64-80 My), and eutherian wide (81-150 My). Finally, we used this data to calculate the substitution rates of DNA transposons for each category and refine the age of each family based on the average percent divergence of individual copies to their consensus. Based on these combined methods, we can confidently estimate that at least 40 human DNA transposon families, representing approximately 98,000 elements ( approximately 33 Mb) in the human genome, have been active in the primate lineage. There was a cessation in the transpositional activity of DNA transposons during the later phase of the primate radiation, with no evidence of elements younger than approximately 37 My. This data points to intense activity of DNA transposons during the mammalian radiation and early primate evolution, followed, apparently, by their mass extinction in an anthropoid primate ancestor.

Figure 1.

Cumulative copy numbers for DNA element superfamilies and L1 elements according to age. The age of each family is plotted against the cumulative copy number of the superfamily. See Results and Methods sections for details on the calculation of the age for each family. (1) hAT superfamily elements were more intensively active during the pre-prosimian era (>63 My), decreasing in proliferation during the subsequent primate radiation (<63 My). (2) MuDR and piggyBac (e.g., MER85) superfamily elements were strictly active during the primate radiation. (3) Tc1/mariner (e.g., MADE1, Tigger1) superfamily elements were active before the primate radiation, but experienced a marked burst of activity during the primate radiation.

Figure 2.

Comparison of three independent methods for dating DNA transposons. Eleven distinct families of DNA transposons were shown to be primate specific by all three methods. Twenty-nine additional DNA element families were found to be primate specific by both the percent divergence and cross-species genomic analysis methods. Twenty-nine families predicted to be primate specific based solely on percent divergence and age were determined to be eutherian-wide by cross-species analysis.

Figure 3.

Summary of the activity of DNA transposons through primate evolution. The bar graph at the bottom of the figure represents the number of DNA elements active during each major lineage, broken down per superfamily. Note that no DNA elements were found to be active after the emergence of new world monkeys.