A Biologically Active Family of Human Endogenous Retroviruses Evolved from an Ancient Inactive Lineage

Human endogenous retroviruses (HERVs) are remnants of ancient germ line infections that now make up a substantial fraction of the human genome. While most HERVs are inactive, there is a growing body of evidence that implicates some members of the HERV-K family of elements as being transpositionally active. Here we report the results of a phylogenetic survey of HERV-K LTR sequences. We have elucidated the evolutionary relationships among the youngest, most recently active (human specific) lineage of HERV-K elements and a number of more ancient lineages. Levels of sequence variation were used to estimate the ages of the different phylogenetic groups of element sequences. Our results suggest that a burst of transpositional activity led to the emergence of the human specific lineage of HERV-K elements and coincided with the time humans and chimps are believed to have diverged from a common ancestor ∼6 million years ago. In addition, as noted previously, the youngest HERV-K subfamily shows a within-group pattern of variation where younger, more recently active subgroups are successively derived (evolve) from older subgroups. However, among HERV-K subfamilies there is no such correlation between phylogenetic relationship and the age of the groups. In fact, the oldest subfamily of HERV-K elements studied here appears to have given rise to the youngest and most recently active group of elements. This suggests that ancient families of HERVs may be capable of retaining the potential for biological activity over long spans of evolutionary time.