Human Endogenous Retroviruses: Expression and Evolutionary Relationships

Abstract: The human genome contains genetic elements which are more or less similar to infectious retroviruses. These are called human endogenous retroviruses (HERVs) and are thought to be remnants of infections in the primate lineage. Most of them have been inserted 10 to 60 million years ago but have at different time points spread in the genome via intracellular retrotransposition and make up as much as 7 % of the human genome. It is not known whether these elements have any biological function or are involved in any disease. The thousands of HERV elements in the human genome have been divided into class I, II and III elements according to their similarities to different exogenous retroviruses. We have in this thesis been working with class II HERVs. Elements in this class have similarities to type A, B, D and avian type C retroviruses. We have classified these elements into ten groups. We have also shown that one of these groups, HML-1, was integrated into the genome 30 to 45 million years ago, while another class II group, HML-3 was present in a few copies more than 45 million years ago and subsequently expanded in the genome of the Old World monkey/hominoid lineage. Yet another group, members of the HML-5 group were present in multiple copies at least 45 million years ago and may be the oldest class II HERVs. We have in this thesis also shown that the class II elements have a heterogenous expression among individuals in several cell types. This suggests that these elements have retained regulatory elements in their LTRs. We have also shown, by studying the dbEST libraries, that HERV-K(HML-2) is the only class II group with a high expression in human tissues. HML-1, HML-3, HML-5, HERV-K(HML-6) and HERV-K(C4) were expressed in several tissues but to a lower extent. No expression was detected for HML-4 and HML-7 to HML-9.