Expression profiles of endogenous retroviruses in Old World monkeys

Abstract

Human endogenous retroviruses (HERVs) are a major component of the human genome and an active part of the transcriptome. Some HERVs play vital biological roles, while others potentially contribute to diseases. Many HERVs are relatively new in the primate genome, having entered or expanded after the lineages leading to the platyrrhines (New World monkeys) and catarrhines (Old World monkeys and apes) separated. Most HERVs are active in at least some tissues, though tissue specificity is common for most elements. We analyzed multiple tissues from several Old World monkeys using retroviral pol-based DNA microarrays and quantitative PCR methods to determine their ERV expression profiles. The results demonstrate that while many ERVs are active in nonhuman primates, overall the tissue expression specificity is unique to each species. Most striking is that while the majority of HERVs analyzed in this study are expressed in human brain, almost none are expressed in Old World monkey brains or are only weakly expressed.

FIG. 1.

Summary of the expression profiles for ERV families examined in each sample. Tissues and HERVs examined, including the mammalian ERVs BaEV and GaLV, are indicated. The results are shown for the three macaques and the one mandrill examined in this study; results for genomic DNA are also shown and are shaded to distinguish them from the RNA profiles. Human profiles are taken from reference . Tissue samples and HERVs analyzed by quantitative PCR are indicated by superscript “a” and “b”, respectively. ERV taxa were classified as active if at least one member of the taxon was positive.

FIG. 2.

Real-time PCR quantification of ERVs in human, mandrill, and macaque tissues. The threshold value (C_t) data of HERV-K (HML-3), HERV-E, and HERV-W were normalized to the RPII house keeping gene (ΔC_t) for each tissue in (A) macaques 1020, 1021, and 1022, (B) mandrill 1023, and (C) humans. Male and female macaques are designated by an “m” for male or “f” for female after the respective sample number. The lowest ΔC_t value representing the strongest expression of the corresponding element per tissue was arbitrarily set to a value of 1, and all ratios were normalized to give a value between 0 and 1. The standard error is shown. To compare relative fold expression differences among species, the normalized relative expression values of the OWM ERVs HERV-K (HML-3), HERV-E, and HERV-W were compared to that of human tissue (2^−ΔΔCt method [25], also using RPII to normalize the data). Using either macaque 1020 or mandrill as the baseline, each ERV for each tissue in a mandrill and macaque sample was evaluated for either higher, lower, or the same relative expression level as that seen in human tissue. The y axis shows the fold difference expression level of human tissue relative to that of each primate. Standard error bars are shown. Skeletal muscle, kidney, and brain are shown in panels D, E, and F, respectively. (G) The fold difference expression (the y axis) calculated using the 2^−ΔΔCt method for HML-3 and HERV-E among macaques 1020, 1021, and 1022 are shown, whereas macaque 1020 was used as the expression baseline for comparison. The microarray results are summarized below each column with white, gray, and black circles representing absence of signal, weak signal, and strong signal, respectively.