The Bov-A2 retroelement played a crucial role in the evolution of ruminants

The Bov-A2 is one of the most common short interspersed nucleotide elements (SINEs) in ruminants. The genomic distribution and evolution of this retroelement were analysed in order to highlight its possible functional role. Several regions containing an entire Bov-A2 were amplified and polymorphisms were identified by direct sequencing of the amplification products. The obtained sequences were used together with entire Bov-A2 sequences of the public database to analyse their evolutionary pathway. A site-specific micro-recombination followed by gene conversion or unequal crossing-over might be responsible for the high amount of genetic variation of Bov-A2 sequences. Short cDNAs copied by the reverse transcriptase might be the donor sequences for the micro-recombination, according to the RT-mutatorsome mechanism of the somatic hyper-mutation (SHM) process in the hypervariable regions of immunoglobulin and major histocompatibility complex (MHC) genes. The Bov-A2 is generally present in the non-coding regions of several genes preferentially expressed during the cell response to environmental stresses or activation signals. In particular, the presence of Bov-A2 sequence in the 3' untranslated regions of mRNAs involved in cell growth and differentiation during the immune response might be related to an important functional role in the post-transcriptional regulation of gene expression. This hypothesis is supported by the similarity between the conserved "core" sequences motives CACTn (n = 3, 4, 3) of Bov-A2 and elements affecting the messengers stability as several microRNAs (miRNAs). Using primers based on the "core" sequence and bovine, ovine and human cDNAs in RT-PCR experiments, we demonstrate that the mRNAs containing the "core" sequence are present at high levels in lymphocytes only after their activation. Our results suggest the existence of a system based on environmental and epigenetic signals that is able to spread and mutate the Bov-A2 sequence in the genes expressed during the response to cellular activation signals. By means of this adaptive system a reverse flow of information from environment to genes might reinforce and diversify the stress response at cellular and individual levels.