Javier Costas




Human endogenous

retroviruses arose from germ-line retroviral integrations at different times

during evolution.  After their initial integrations, retroviral sequences are

transmitted vertically and they may proliferate by retrotransposition (or

re-infection).  This intragenomic spread implies a process of co-evolution

between the endogenous retrovirus and the host genome.  As shown in the examples

below, this process differs substantially from one HERV family to others.


We initially analyzed the

evolutionary history of ERV9 by using LTR sequences taken from the human

genome.  We classified these insertions into 14 subfamilies based on several

characteristic nucleotide differences.  The age of each subfamily was

approximately estimated based on the average sequence of its members from the

subfamily consensus sequence.  Determination of the sequential order of

diagnostic substitutions led to the identification of four distinct lineages. 

Strong evidence for mosaic evolution of some of these lineages is presented.  We

conclude that ERV9 has been actively spreading within the genome of the lineage

leading to humans over a long period of primate evolution.


When we applied the same

methodology to study the evolutionary history of HERV-W, a totally different

picture appeared.  Identification of shared diagnostic differences and

phylogenetic analyses revealed the existence of just three subfamilies.  The

average divergence between sequences for each one of the subfamilies suggests

that most of the HERV-W elements were inserted within the genome during a short

period of time.  Remarkably, each one of the subfamilies consists of two types

of insertions, the expected proviral sequences and other sequences with

structural features of processed retrogenes.  In fact, the lower evolutionary

success of HERV-W in comparison with ERV9 might be related to the existence of a

considerable proportion of genomic RNA sequestered by the L1 machinery.


Although ERV9 has been

actively transposing during an extended period of primate evolution, it seems

that HERV-K represents the unique known case of endogenous retrovirus that

amplified in the human genome after the divergence of human and chimpanzee

lineages.  Here, we also present comparative analyses about the youngest

insertions of ERV9 and HERV-K, suggesting again two contrasting histories. 

While several lineages of HERV-K proviruses remained transpositionally active

after the humans/chimpanzee split, the last insertional events of ERV9 seems to

be due to the activity of only one active sequence.