Why are evolutionary biologists bringing back extinct deadly viruses?
That's an interesting question. See also the audio interview, in which the author "discusses what retroviruses can teach biologists about how humans evolved, and how they may hold the key to conquering AIDS and other diseases." See also coverage in Discover, complete with electron micrographs. I especially liked this anecdote: Harmit Malik grew up in Bombay and studied chemical engineering at the Indian Institute of Technology there, one of the most prestigious technical institutions in a country obsessed with producing engineers. He gave no real thought to biology, but he was wholly uninspired by his other studies. "It was fair to say I had little interest in chemical engineering, and I happened to tell that to my faculty adviser," he recalled. "He asked me what I liked. Well, I was reading Richard Dawkins at the time, his book 'The Selfish Gene'” -- which asserts that a gene will operate in its own interest even if that means destroying an organism that it inhabits or helped create. The concept fascinated Malik. “I was thinking of becoming a philosopher," he said. "I thought I would study selfishness." Malik’s adviser had another idea. The university had just established a department of molecular biology, and Malik was dispatched to speak with its director. “This guy ended up teaching me by himself, sitting across the table. We met three times a week. I soon realized that he was testing out his course on me. I liked it and decided to apply to graduate school -- although I had less than a tenth of the required biology courses. I had very little hope." But he had excellent test scores and in 1993 was accepted at the University of Rochester, as a graduate student in the biology department. He visited his new adviser as soon as he arrived. "He looked at my schedule and said, 'I see that you are doing genetics.' I had no clue what he was talking about, but I said sure, that sounds good. I had never taken a course in the subject. He gave me the textbook and told me that the class was for undergraduates, which made me feel more comfortable." It wasn’t until the end of the conversation that Malik realized he would be teaching the class, not taking it.
Here are a few papers: Discovery and analysis of the first endogenous lentivirus The lentiviruses are associated with a wide range of chronic diseases in mammals. These include immunodeficiencies (such as HIV/AIDS in humans), malignancies, and lymphatic and neurological disorders in primates, felids, and a variety of wild and domesticated ungulates. Evolutionary analyses of the genomic sequences of modern-day lentiviruses have suggested a relatively recent date for their emergence, but the failure to identify any endogenous, vertically transmitted examples has meant that their longer term evolutionary history and origin remain unknown. Here we report the discovery and characterization of retroviral sequences belonging to a new lentiviral subgroup from the European rabbit (Oryctolagus cuniculus). These viruses, the first endogenous examples described, are >7 million years old and thus provide the first evidence for an ancient origin of the lentiviruses. Despite being ancient, this subgroup contains many of the features found in present-day lentiviruses, such as the presence of tat and rev genes, thus also indicating an ancient origin for the complex regulation of lentivirus gene expression. Although the virus we describe is defective, reconstruction of an infectious progenitor could provide novel insights into lentivirus biology and host interactions.
Syncytin-A and syncytin-B, two fusogenic placenta-specific murine envelope genes of retroviral origin conserved in Muridae Recently, we and others have identified two human endogenous retroviruses that entered the primate lineage 25-40 million years ago and that encode highly fusogenic retroviral envelope proteins (syncytin-1 and -2), possibly involved in the formation of the placenta syncytiotrophoblast layer generated by trophoblast cell fusion at the materno-fetal interface. A systematic in silico search throughout mouse genome databases presently identifies two fully coding envelope genes, present as unique copies and unrelated to any known murine endogenous retrovirus, that we named syncytin-A and -B. Quantitative RT-PCR demonstrates placenta-specific expression for both genes, with increasing transcript levels in this organ from 9.5 to 14.5 days postcoitum. In situ hybridization of placenta cryosections further localizes these transcripts in the syncytiotrophoblast-containing labyrinthine zona. Consistently, we show that both genes can trigger cell-cell fusion in ex vivo transfection assays, with distinct cell type specificities suggesting different receptor usage. Genes orthologous to syncytin-A and -B and disclosing a striking conservation of their coding status are found in all Muridae tested (mouse, rat, gerbil, vole, and hamster), dating their entry into the rodent lineage {approx}20 million years ago. Together, these data strongly argue for a critical role of syncytin-A and -B in murine syncytiotrophoblast formation, thus unraveling a rather unique situation where two pairs of endogenous retroviruses, independently acquired by the primate and rodent lineages, would have been positively selected for a convergent physiological role.
Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements Human Endogenous Retroviruses are expected to be the remnants of ancestral infections of primates by active retroviruses that have thereafter been transmitted in a Mendelian fashion. Here, we derived in silico the sequence of the putative ancestral "progenitor" element of one of the most recently amplified family—the HERV-K family—and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny. We also show that this element amplifies via an extracellular pathway involving reinfection, at variance with the non-LTR-retrotransposons (LINEs SINEs) or LTR-retrotransposons, thus recapitulating ex vivo the molecular events responsible for its dissemination in the host genomes. We also show that in vitro recombinations among present-day human HERV-K loci can similarly generate functional HERV-K elements, indicating that human cells still have the potential to produce infectious retroviruses.
Annals of Science: Darwin’s Surprise |
