The role of genes domesticated from LTR retrotransposons and retroviruses in mammals

Abstract

The acquisition of multiple genes from long terminal repeat (LTR) retrotransposons occurred in mammals. Genes belonging to a sushi-ichi-related retrotransposon homologs (SIRH) family emerged around the time of the establishment of two viviparous mammalian groups, marsupials and eutherians. These genes encode proteins that are homologous to a retrotransposon Gag capsid protein and sometimes also have a Pol-like region. We previously demonstrated that PEG10 (SIRH1) and PEG11/RTL1 (SIRH2) play essential but different roles in placental development. PEG10 is conserved in both the marsupials and the eutherians, while PEG11/RTL1 is a eutherian-specific gene, suggesting that these two domesticated genes were deeply involved in the evolution of mammals via the establishment of the viviparous reproduction system. In this review, we introduce the roles of PEG10 and PEG11/RTL1 in mammalian development and evolution, and summarize the other genes domesticated from LTR retrotransposons and endogenous retroviruses (ERVs) in mammals. We also point out the importance of DNA methylation in inactivating and neutralizing the integrated retrotransposons and ERVs in the process of domestication.

Keywords: LTR retrotransposons and ERVs; development and evolution; domesticated genes; mammals.

FIGURE 1

Endogenous retrovirus, LTR retrotransposon and their domesticated genes. Top: an endogenous retrovirus, HERV-W, and SYNCYTIN 1. SYNCYTIN 1 retains LTRs at both ends and the Env gene, while the Gag and Pol genes do not support ORFs corresponding functional proteins because of stop mutations. Bottom: an LTR retrotransposon, sushi-ichi, and the domesticated PEG10 and PEG11/RTL1 genes. Both PEG10 and PEG11/RTL1 have lost LTRs while entire regions exhibit significant homologies to the Gag and Pol genes remaining in some of the retrotransposon domains. The -1 frameshift mechanism is conserved in PEG10. LTR, long terminal repeat; Gag, group-specific antigen; Pol, polymerase; Env, envelope; CCHC, RNA-binding motif; DSG, protease active site; YYDD, reverse transcriptase; DAS, RNase highly conserved motif; HHCC, integrase DNA binding motif; DDE, strongly conserved integrase.

FIGURE 2

Mouse mature placenta. Left: mouse placenta is composed of labyrinth, spongiotrophoblast, and giant cell layers. Right: magnified view of the labyrinth layer. In the labyrinth layers, fetal capillaries are surrounded by three layers of trophoblast cells and are bathed in maternal blood, functioning as a site of nutrient and gas exchange between the fetal and maternal blood.

FIGURE 3

Domestication from LTR retrotransposons and ERVs in mammals. The acquisition of SASPase occurred in a common mammalian ancestor. PEG10 was domesticated in a common therian ancestor while PEG11/RTL1, SIRH3–11, and PNMA1–19 were domesticated in a common eutherian ancestor with subsequent loss of some of the PNMA genes in rodents. The ESCAN domain was domesticated in lower vertebrates and its transition to the SCAN domain took place by combining with the zinc finger and/or KRAB motifs which had already occurred in certain reptiles. In any event, the expansion of SCAN family is obvious in the eutherians. SIRH12 and PNMA-MS1 are derived from marsupialspecific domestication events. The SYNCYTINs were independently recruited in several different mammalian lineages. The eutherians and marsupials are viviparous, having chorioallantoic and choriovitelline placentas (yolk sac placentas), respectively. Both PEG10 and PEG11/RTL1 are essential for the proper formation of efficient chorioallantoic placentas.