Thursday, December 06, 2007

Evolution: Its in Your Genes

Viruses are unique in the world. So unique that some biologists do not consider them alive. The tiny "things" are smaller than bacteria and so simple that they are made of only a protein shell and nucleic acids. One characteristic they share with more complex forms is that they reproduce themselves. Retroviruses perform this essential function by invading a healthy germ cell and using a special enzyme to cause the invaded cell to produce viral DNA from it's own RNA. The DNA from the viral source becomes part of the germ cell's DNA. This process is the reverse of normal cellular activity in which nuclear DNA is translated into mitochondrial RNA for the production of proteins. The production of more viruses by the host induces disease, such as influenza [image], smallpox or AIDS. Howard Temin and David Baltimore, working separately, found the viral enzyme that allows the reverse transcription. They were awarded the Nobel Prize for Medicine in 1975 for finding the enzyme reverse transcriptase.

We only need about 2% of our genetic code to produce our basic molecular building blocks, proteins. The rest of of our code is filled with duplication, apparently useless nucleotide pairs, and other "junk" DNA. Molecular biologists are now discovering that the genome contains another extremely interesting artifact: the genetic remains of retroviruses that the human species has successfully combated down the millennium. Biologists are hunting for the "fossilized" remains of long extinct viruses that managed to insert themselves into our germ cells and be inherited from our remote ancestors going back millions of years. These fragments are named endogenous retroviruses because once they enter a species genetic code, they remain there for as long as the species exists. According to Michael Specter writing in the New Yorker magazine, when the human genome was mapped in 2003 as much as 8% of the human genome was discovered to consists of once retroviral DNA that has entered the human code. One endogenous retrovirus, extinct for hundreds of thousands of years, was brought back into existence last year by Thierry Heidmann working at the Gustav Roussy Institute outside Paris. The Frankensteinian experiment was conducted to prove that a resurrected retrovirus could be constructed from it's fragmentary remains and remain infectious. The 'frankenvirus' proved to be exactly that, causing human, hamster and cat DNA to produce copies of retroviral DNA. A new discipline has been created too, paleovirology, which studies the genetic history of ancient viruses and their impact on human development.

Molecular biologists, including Heidmann, have suggested that without endogenous retroviruses mammals might not have developed a placenta that protects an embryo from attack and gives it time to mature. In the early seventies, scientist scanned baboon placentas with an electron microscope and found retroviruses on the layer of the tissue known as the syncytium which is the barrier between mother and fetus. The same phenomenon was discovered in mice, cats, pigs and humans. The import of the discovery was not appreciated at the time. But now cell fusion is known as a fundamental process of mammalian placentas and endogenous retroviruses. Syncytin causes placenta cells to fuse together and employs the exact same chemical mechanism that allows retroviruses to bond with the cells they attack.

When Darwin said that man shared a common ancestor with apes, he could not know that the most convincing evidence of our shared lineage would be found in our genes in the form of endogenous retroviruses. They provide a thread of molecular remnants that goes back millions of years--enough time to measure evolutionary change. We share 98% of our genes with modern bonobos. We also share, in thousands of places on our genome, the fragments of extinct retroviruses. The human genome consists of three billion pairs of nucleotides. It makes logical sense that the only way we could share, at seemingly thousands of random locations, the exact same retroviral DNA with another species is by inheriting it from a common ancestor. One of the frustrations of the HIV epidemic is that although the source of this particular retrovirus is known to be from chimpanzees, they do not get sick from the virus. The vital difference appears to be in their genes. They have a hundred thirty copies of pan troglodytes endogenous retrovirus (PtERV). We have none. We survived the PtERV infection of four million years ago, but modifications to our code has left us vulnerable to HIV. Lucky chimps.

[electron micrograph image credit: Linda M. Stannard]