Paleovirology of ‘ syncytins ’, retroviral env genes exapted for a role in placentation

Abstract

One contribution of 13 to a Theme Issue 'Paleovirology: insights from the genomic fossil record'. The development of the emerging field of 'paleovirology' allows biologists to reconstruct the evolutionary history of fossil endogenous retroviral sequences integrated within the genome of living organisms and has led to the retrieval of conserved, ancient retroviral genes 'exapted' by ancestral hosts to fulfil essential physiological roles, syncytin genes being undoubtedly among the most remarkable examples of such a phenomenon. Indeed, syncytins are 'new' genes encoding proteins derived from the envelope protein of endogenous retroviral elements that have been captured and domesticated on multiple occasions and independently in diverse mammalian species, through a process of convergent evolution. Knockout of syncytin genes in mice provided evidence for their absolute requirement for placenta development and embryo survival, via formation by cell-cell fusion of syncytial cell layers at the fetal-maternal interface. These genes of exogenous origin, acquired 'by chance' and yet still 'necessary' to carry out a basic function in placental mammals, may have been pivotal in the emergence of mammalian ancestors with a placenta from egg-laying animals via the capture of a founding retroviral env gene, subsequently replaced in the diverse mammalian lineages by new env-derived syncytin genes, each providing its host with a positive selective advantage.

Retroviral envelope syncytin capture in an ancestrally diverged mammalian clade for placentation in the primitive Afrotherian tenrecs

“…This process would account for the diversity in the nature and age of the captured syncytins that presently can be identified, concomitant with the diversity of placental architectures (2,18,19). Whatever the fine details of the proposed evolutionary scenario might be, a necessary outcome is that syncytins should be found in every mammal with a placenta.…”

“…2). We therefore proposed that syncytins should be present in all placental mammals and that the capture of a founding syncytin by an oviparous ancestor was pivotal for the emergence of placentation more than 150 Mya.…”

Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes

“…Finally, studies in palaeovirology are increasingly revealing how viruses have contributed to the gene repertoires of their hosts. Indeed, although relatively few EVE-derived host genes have been characterized in detail so far [19][20][21][22], numerous EVEs are transcribed and/or have evolved under purifying selection after endogenization [10,11,[23][24][25], suggesting they may have been domesticated and now fulfil cellular functions in the host.…”

Novel and divergent genes in the evolution of placental mammals

“…Genomic 49 changes that could contribute to phenotypic change include changes to cis-regulatory DNA, 50 changes to repetitive DNA landscapes, and the origin and loss of coding and non-coding 51 genes. In addition, co-option of genes from integrated retroviruses has been shown to be 52 important in eutherian mammal evolution, generated syncytin genes deployed to facilitate 53 cellular fusion during placentation [6]. Here we investigate the extent to which novel protein- 54 coding genes arose on the stem lineage of the placental mammals, during the first~60-80 55 3 | P a g e million years of eutherian evolution, and whether novel genes likely contributed to the 56 emergence of the unique phenotypic characters of placental mammals.…”