Discovering Retroviruses Beacons in the Biosphere

In the already unusual world of viruses, retroviruses stand out for being even more so. Called “retro” because they reverse the flow of genetic information from RNA to DNA, rather than the normal DNA to RNA, they have turned out to be ancient, omnipresent, and incredibly influential. They are also important as they cause diseases such as AIDS. With Discovering Retroviruses, Anna Marie Skalka delivers a book dedicated to this particular group that is as technical as it is fascinating.

I was really looking forward to this book and have mentioned it a number of times in previous reviews as several authors have highlighted that retroviruses are something quite special (see e.g. Viruses and Virusphere). Where normal viruses commandeer the host’s biomolecular machinery for their reproduction, retroviruses are even more intimately entwined with their hosts, transferring their genetic information to them.

Skalka first sets the stage with a short history of genetics, from Mendel to Crick and onwards to the “central dogma” (see Unravelling the Double Helix for more). That dogma refers to the finding that DNA is copied into single-stranded RNA which is then translated, three letters at a time, into amino acids that, when strung together, make up the workhorses of the cell: proteins. It has become a cornerstone of genetics. And exactly because of this, many scientists were not ready to accept the first suggestions in 1964 that retroviruses do it backwards, turning their little RNA genome into a string of DNA that becomes part of the host genome. Rather than a textbook approach that lays out the facts, Skalka chooses to tell the story chronologically, following the timeline of discoveries and introducing all the key players.

As also mentioned in Human Errors, modern sequencing technology has revealed that our DNA is littered with remnants of retroviruses, many of which have become inactive and have suffered random mutations. The numbers are quite staggering: whereas ~1% of the human genome codes for all the proteins that make us tick, another 8% is of retroviral origin and larger fractions still consist of other jumping elements and so-called retrotransposons. Slowly but surely, what was initially deemed junk actually has a function (see also Junk DNA and The Deeper Genome).

For one, this extra DNA offers hotspots of so-called recombination (i.e. the re-arranging of parts of an organism’s genetic material), which is one way to generate the genetic variation on which evolution can act. In the process, things sometimes break and diseases are caused. But it is not all bad news. Skalka details how this extra genetic material has been co-opted by our immune system; has added the digestive enzyme amylase, found in the pancreas, to our salivary glands allowing us to digest starch better; and has also been involved in the evolution of the placenta. Liam Drew asked the question: “what makes us mammal?” (see my previous review of I, Mammal). One of his answers was: “the placenta did”. But ultimately, as Skalka shows here, retroviruses did. Without them, the placenta would not have happened. And, amazingly, mammals evolved them on five independent occasions!

There are other fascinating revelations about evolution throughout the book. Retroviruses may have very well been a necessary link in the transition from an RNA world (which is how many scientists believe life started, see Life from an RNA World) to a DNA world. I was similarly fascinated to read more about the use of retroviruses as an independent line of evidence when drawing up phylogenetic trees (i.e. family trees based on molecules such as DNA). As stretches of retroviral DNA are initially inserted in identical pairs, one way to mine them for information is by comparing mutation rates. This can reveal a timeline of when certain infections occurred and whether this happened before of after two species evolved to become separate. (My explanation leaves out some subtleties, Skalka goes into far more detail)

Two further chapters give detailed accounts of how retroviruses have been implicated in causing both certain cancers and AIDS. Especially the chapter on AIDS and HIV goes into great detail on the biochemical and genetic basis of the disease, the development of drugs, the scary denialism propagated by a small minority (see also Pseudoscience), and the research that traced the origin to a virus that jumped from primates to humans in the 1900s (see also Virus Hunt). And, as opposed to Viruses and Virusphere, Skalka does describe the recent discovery and developments around CRISPR, which consists of viral DNA stored in the host as a kind molecular vaccination card (see also A Crack in Creation).

Discovering Retroviruses is a short book, but it is dense and quite technical. I found I had to give it my full attention, sometimes going over certain passages twice to make sure I understood them. The readability is slightly hampered by the many abbreviations and gene and protein names that come with this field (a glossary would have been welcome in that regard), but that is made up for by a large number of clear colour illustrations that are very helpful in schematically showing how certain mechanisms work. The chronological format also means that you have to tease some of the details out of the narrative, although Skalka does an excellent job summarising things at the end of each chapter, and in her epilogue. As far as I know, Skalka’s is the first book on this topic aimed at a wider readership. If you have a serious interest in viruses, and retroviruses in particular, this well-researched and scholarly book is a must-read.