to a study published in 2005, no HERVs capable of replication had been identified; all appeared to be defective, containing major deletions or nonsense mutations (not true for HERV-K). This is because most HERVs are merely traces of original viruses, having first integrated millions of years ago. An analysis of HERV integrations is ongoing as part of the 100,000 Genomes Project. Human endogenous retroviruses were originally discovered when human genomic libraries were screened under low-stringency conditions using either probes from animal retroviruses or by using oligonucleotides with similarity to virus sequences. Classification HERVs are classified based on their homologies to animal retroviruses. Families belong to Class I are similar in sequence to mammalian Gammaretroviruses (type C) and Epsilonretroviruses (Type E). Families belonging to Class II show homology to mammalian Betaretroviruses (Type B) and Deltaretroviruses (Type D). Families belong to Class III are similar to foamy viruses. For all classes, if homologies appear well conserved in the gag, pol, and env gene, they are grouped into a superfamily. There are more Class I families known to exist. The families themselves are named in a less uniform manner, with a mixture of naming based on an exogenous retrovirus, the priming tRNA (HERV-W, K), or some neighboring gene (HERV-ADP), clone number (HERV-S71), or some amino acid motif (HERV-FRD). A proposed nomenclature aims to clean up the sometimes paraphyletic standards. Origin Sometime during human evolution, exogenous progenitors of HERV inserted themselves into germ line cells and then replicated along with the host's genes using and exploiting the host's cellular mechanisms. Because of their distinct genomic structure, HERVs were subjected to many rounds of amplification and transposition, which lead to a more widespread distribution of retroviral DNA. Nevertheless, one family of viruses has been active since the divergence of humans and chimpanzees. This family, termed HERV-K (HML2), makes up less than 1% of HERV elements but is one of the most studied. There are indications it has even been active in the past few hundred thousand years, e.g., some human individuals carry more copies of HML2 than others. Traditionally, age estimates of HERVs are performed by comparing the 5' and 3' LTR of a HERV; however, this method is only relevant for full-length HERVs. A recent method, called cross-sectional dating, uses variations within a single LTR to estimate the ages of HERV insertions. This method is more precise in estimating HERV ages and can be