Retroviruses turned egg-layers into live-bearers

The protein syncytin, which is essential for formation of the placenta, originally came to the genome of our ancestors, and those of other mammals, via a retrovirus infection. Placental structures have also developed in non-mammalian vertebrates. The Mabuya lizard (pictured: image credit), which emerged 25 million years ago, has a placenta very much like those in mammals, and its development was likely driven by capture of a retroviral gene.

The genetic material of retroviruses is RNA, but during infection it is converted to DNA which then integrates into the chromosome of the cell. If the infected cell happens to be a germ cell, then the viral DNA, now called called an endogenous retrovirus, becomes a permanent part of the animal and its offspring. One of the retroviral genes, env, encoding the viral glycoprotein, has been repurposed by mammals to become the syncytin genes. These encode fusogenic proteins that are involved in the formation, by cell-cell fusion, of the syncytiotrophoblast.

Syncytins are present in all placental mammals, leading to the hypothesis that retroviral infection has driven the evolution of placental mammals from egg laying species.

Placentas are not limited to mammals – they emerged in other vertebrates, including in certain lizards in the family Scincidae. In one genus, Mabuya, (pictured), the placenta is structurally similar to the mammalian placenta.

Examination of placental RNA from the Mabuya lizard revealed the presence of transcripts from retroviral-like env genes. They are part of ancient retroviral genomes integrated in the lizard genome. The encoded proteins are synthesized in the placenta, and are fusogenic – they can cause fusion cells in which they are produced. The receptor for these lizard syncytins was identified, and shown to be also present in the placenta.

The first placenta-like structures probably arose in egg-laying vertebrates, around 400 million years ago in fish, 150 million years ago in mammals, and 25 million years ago in Mabuya lizards. It seems likely that these events took place after retrovirus infection followed by capture of env genes, which allowed fusion of cells in the placenta. This repurposing of a retroviral gene occurred randomly and rarely in evolution, but it clearly imposed an advantage, as placental-mediated live birthing has endured.

Without retroviruses, many species might still be laying eggs – and that includes humans.