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Sunday, March 10, 2013

Retroviruses


In Chapter VI (“Jump into the Gene Pool”), from pages 147-150, Dr. Moalem discusses the relation between retroviruses and the evolution of DNA. Retroviruses relate to Big Idea 3 (Living systems store, retrieve, transmit, and respond to information essential to life processes), as the transfer of genetic information from retrovirus to host introduces genetic variation within the host.

First, describe how retroviruses work, and explain how retroviruses are different from other viruses. How do retroviruses change our understanding of the central dogma of molecular biology? Next, describe the similarities between the mechanisms of retrotransposons and retroviruses. Why are these similarities significant, in an evolutionary perspective? Dr. Moalem describes how 8 percent of the human genome is composed of retroviruses, called HERVs – research one of these elements and explain its connection to gene expression.

(Posted by Matthew Zhang, mzhang4@students.d125.org)

2 comments:

  1. Retroviruses, viruses of the taxonomic class Retroviridae, are a specific type of RNA virus that replicates within a host cell be rewriting the host cell’s DNA. Working in the opposite direction of the normal pattern (the normal pattern being DNA -> RNA -> Protein), retroviruses utilize the enzyme Reverse Transcriptase to convert their RNA code into DNA. Once the RNA has been reverse transcribed, the new virus-infused DNA is integrated into the host’s genome via an integrase enzyme. Cells then replicate, passing on the new, mutated DNA that has been altered by the retrovirus, thus fulfilling the retrovirus’ desire to survive and reproduce. This is different than the reproductive mechanism for a regular virus, which simply replicates in addition to the host cell’s DNA and without using Reverse Transcriptase to replace the original eukaryotic genetic code.

    Retrotransposons are a subclass of transposons; transposons (a.k.a. transposable elements) are sequences of DNA that can relocate within a eukaryotic genome. Often considered “Junk DNA”, transposons (a.k.a. “jumping genes”) were discovered by Barbara McClintock while she was working with corn, for which she won the Nobel Prize in 1983. What separates retrotransposons from other transposons is their method of relocation: while regular transposons can insert, delete, or translocate segments of DNA, retrotransposons actually rewrite genomic sequences in a very similar manner to that which is employed by retroviruses. According to Dr. Sharon Moalem on page 150 of Survival of the Sickest, retrotransposons are first transcribed into RNA by RNA Polymerase II before the Reverse Transcriptase enzyme ‘pastes’ the retrotransposon sequence into the eukaryotic genome at the precise location that the retrotransposon ‘wants’ to go (as genetic material cannot ‘want’ anything, it is more precise to say that the location is that to which the chemical signals have indicated the retrotransposon should reverse transcribe).

    From an evolutionary perspective, these similarities are significant in that they suggest that retrotransposons may have evolved from retroviruses; as an implication thereof, the eukaryotic genome may have evolved from millions upon millions of bacterial retroviruses. This can possibly be explained using concepts covered under Big Idea #1, the idea that the process of evolution drives life and produces all of life’s diversity. While the eukaryotic genome was young, it is likely that it was subjected to these retroviruses that reverse transcribed themselves into the genetic information, creating mutations in the DNA. However, given the multitude of likely mutations, it is likely that some had positive effects on the fitness of the eukaryotic population, resulting in increased survival rather than the regular increased mortality generally associated with viruses. As the eukaryotic genome evolved, these portions of DNA that were reverse transcribed from retroviruses likely retained some elements of their previous abilities, resulting in retrotransposons.

    (continued in next post)

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  2. Beyond speculation, it has been conclusively proved that “8 percent of the human genome is composed of retroviruses and related elements” (Moalem 150). These different retrovirus-born parts of the human genome are known as HERVs – human endogenous retroviruses (endogenous meaning ‘caused by factors inside of the organism’, according to www.webster.com). HERV-K is the most biologically active class of a human endogenous retrovirus. HERV-K, according to numerous journal articles published on the SBIR and NCBI websites, has been identified as being overexpressed in cancerous patients, especially those suffering from leukemia, breast cancer, and melanoma. Current speculation is that the HERVs from the HERV-K family, through whatever mechanism it may be (acetylation, retrotransposons, etc.), environmental factors that turn ‘on’ the genes coded for by HERV-K sections produce an abundance of protein that can be detrimental to an individual’s health. This speculation is backed up by research conducted on leukemia patients, which showed increased concentration of antibodies specific to known leukemia antigens. Little beyond this basic connection is known, but additional research is currently ongoing as to the specifics of human endogenous retrovirus gene expression.

    (Justin Millman, jmillma4@students.d125.org)

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