Endogenous retroviruses provide the primary polyadenylation signal for two new human genes (HHLA2 and HHLA3).

By screening the expressed sequence tag (EST) database, we identified transcripts of two new human genes that are polyadenylated within a long terminal repeat (LTR) of the HERV-H endogenous retrovirus family. The first gene, termed HHLA2, is represented by two EST clones and one cDNA clone, all of which have a polyadenylated LTR as their 3' end. The gene has an open reading frame (ORF) of 414 amino acids with three immunoglobulin-like domains and is expressed primarily in intestinal tissues, kidney, and lung. Seven small EST clones from several different tissues were found for the second gene, termed HHLA3. As with HHLA2, all HHLA3 ESTs utilized a HERV-H LTR as the polyadenylation signal. Three types of alternatively spliced HHLA3 transcripts that could encode proteins of 76, 121, or 153 amino acids were detected. Interestingly, the ORF for two of these transcripts continues into the LTR. For both HHLA2 and 3, no major human transcripts that utilized a non-LTR polyadenylation signal were detected. Analysis of RNA from baboon, which lacks the LTRs at these genomic loci, showed that the baboon HHLA2 and 3 genes use other polyadenylation signals. This study demonstrates that ancient retroviral insertions have assumed gene regulatory functions during the course of human evolution. Copyright 1999 Academic Press.