Wednesday, March 26, 2014

A virus, a worm, and a louse walk into a bar

Since large DNA viruses are in the business of making large amounts of DNA, it shouldn't come as a surprise that many of them carry a gene for ribonucleoside diphosphate reductase, the enzyme that allows deoxy-bases (dADP, dCDP, etc.) to be created for use in deoxyribonucleic acid (DNA). The host organism, of course, has its own reductases for this purpose. But you have to imagine that when a giant DNA virus comes barging into a host cell and begins its crash program of digesting host nucleic acids into monomers (free nucleotides), the virus has a huge need to convert those monomers, quickly, into the deoxy form.

So I wasn't totally surprised to find that the genome for PBCV-1, the virus that infects Chlorella algae, contains genes for RNDR (ribonucleoside diphosphate reductase). What's surprising is that the virus brings not one, but two such genes. One gene encodes a short protein (about 370 amino acids); another gene encodes a protein with 771 amino acids. In the case of Paramecium bursaria Chlorella virus NY2A (PBCV-NY2A), which is essentially a variant of PBCV-1, there's actually a third gene, for a protein having 1,103 amino acids.

Why so many genes?

It turns out there are three major types of RNDR enzyme in living organisms, and a given organism can have more than one type. There's an aerobic enzyme (class I) that uses a tyrosine oxygen for radical generation. There's a larger (~1200 AA) class II enzyme that requires adenosylcobalamin (B12) as a coenzyme. And there's an anaerobic class III enzyme that relies on S-adenosylmethionine (SAMe) as a cofactor. Based on the relative sizes of these various enzymes, it appears the PBCV-NY2A virus may be harboring all three. However, most phyocodnaviruses infecting algae seem to have class I and class III reductases, but not the bigger class II.

Human body louse.
The more-or-less standard assumption, when a virus has an enzyme that the host also has, is that the virus obtained its copy of the gene from the host (at some point in the distant or not-so-distant past). That assumption may have to be revisited for PBCV-1's class III reductase. When you do a protein alignment of the viral reductase against the sequence for the host alga's reductase, you expect to see a lot of sequence similarity. What you find in the case of PBCV-1 vs. Chlorella is that the host enzyme shares only 48% amino-acid identities with the viral enzyme. "Well," you're saying, "but that's pretty good, right?" Not so fast. When you take the virus's enzyme sequence and run a search against the entire UniProt.org database, the most similar non-viral sequence turns out to be the reductase enzyme not of the virus's host (Chlorella) but of Haemonchus contortus, the barber-pole worm, with 53% sequence identities. Also very closely matched: the reductase from Pediculus humanas, the human body louse. Three other organisms also have a closer match of their reductases to the PBCV-1 reductase than Chlorella. (See table further below.)

So did this marine-virus reductase gene actually come from a louse, a worm, or a fungus, rather than from an algal host? Not likely. What's going on here, then? Frankly, it's a mystery. For one thing, we have no way of knowing how ancient the PBCV-1 reductase gene is or how fast it has evolved over the ages, relative to the host gene. Some scientists believe the three classes of ribonucleotide reductase originally stemmed from a common ancestor that was similar to the current class III (anaerobic) enzyme. This makes sense, in that the enzyme probably first came about in a highly anoxic ocean environment, billions of years ago, well before atmospheric oxygen began to accumulate, and maybe before sea water had accumulated much dissolved oxygen gas. The PBCV-1 virus reductase may derive from this ancient design. It's possible that Chlorella and its ancestors evolved extensively over the last few hundred million years, whereas the barber-pole worm and body louse (whose ancestors got the ancient class III proto-enzyme) may not have evolved as rapidly. Therefore, the worm enzyme, the louse enzyme, and the viral enzyme may all still share similarities with the progenitor enzyme that Chlorella no longer shares.

But there are also the forces of selection to consider. Modern ribonucleoside reductases incorporate allosteric control mechanisms that fine-tune the enzyme's capabilities with respect to deoxynucleotide (and small-peptide) concentrations. For example, a 50-amino-acid region at the beginning (N-terminal) end of the enzyme allows the enzyme to be feedback-inhibited by dATP. A virus interested in maximizing the production of deoxy-nucleotides might not want or need this sort of allosteric feedback mechanism. Also, the G+C content of the viral genome is significantly lower than that of the host  (40% vs. 60%), meaning that the viral enzyme might very well be optimized to produce deoxy-nucleotides in different ratios than the normal NTP-pool setpoints desired by the host. In short, it's possible to imagine that the virus's nucleotide requirements are, in fact, much more like a barber pole worm's than those of a healthy Chlorella.

Still, you have to admit: Nature comes up with strange bedfellows.

Here are a few protein matches between PBCV-1 (virus) reductase and other reductases:

Organism Length %ID Score E-value Gene identifier
Paramecium bursaria Chlorella virus 1 (PBCV-1) 771 100% 4727 0 A629R
Acanthocystis turfacea Chlorella virus Canal-1 763 76% 3746 0 Canal-1_104L ATCVCanal1_104L
Haemonchus contortus (Barber pole worm) 795 53% 2513 0 HCOI_01437900
Pediculus humanus subsp. corporis (Body louse) 795 53% 2483 0 Phum_PHUM350970
Salpingoeca rosetta (choanoflagellate) 779 51% 2479 0 PTSG_01558
Pneumocystis murina (fungus) 844 51% 2479 0 PNEG_03325
Schizosaccharomyces japonicus (yeast)83451%24780SJAG_04665
Chlorella variabilis (Green alga) 810

48% 2276 0 CHLNCDRAFT_32953
Cellulophaga phage phi13:1 789 47% 2039 0 Phi13:1_gp061
Cyprinid herpesvirus 3 806 45% 2092 0 CyHV3_ORF141 KHVJ151
Acanthamoeba polyphaga moumouvirus 849 43% 1947 0 Moumou_00516

Length refers to the total protein length in amino acids. Percent ID means the percent of target-protein amino acids that were an exact match against (aligned) query-sequence amino acids. Score is a figure of merit for the total matching; E-value represents the expectation that the matches could have occurred by chance (zero, here, in every case; meaning, these similarities probably could not have happened by chance). Finally, the Gene Identifier will let you look up these sequences at UniProt.org or other sequence database sites.

For more on the subject of ribonuceotide reductases in viruses, see the review of phage metagenome RNRs at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3653736/.

96 comments:

  1. Greetings to the general public, Am Mike Amos i want to inform the public how i was cured of HERPES Simplex Virus by a Doctor called Ero. i visited different hospital but they gave me list of drugs like Famvir, Zovirax, and Valtrex which is very expensive to treat the symptoms and never cured me. I was browsing through the Internet searching for remedy on HERPES and i saw comment of people talking about how Doctor Ero cured them. I Was scared because i never believed in the Internet but i was convince to give him a try because i was having no hope of been cured of HERPES so i decided to contact him on his email that was listed on the comment (dreroherbaltreatment@gmail.com ) i searched his email on net and i saw a lot of people testifying about his goodness. when i contacted him he gave me hope and send a Herbal medicine to me that i took and it seriously worked for me, am a free person now without problem, my HERPES result came out negative. I pray for you Dr Ero God will give you everlasting life, you shall not die before your time for being a sincere and great men. Am so happy, you can also contact him if you have any problem Email: dreroherbaltreatment@gmail.com.

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    1. Anonymous9:23 AM


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      i am very grateful sharing this great testimonies with you, The best thing that has ever happened in my life is how i win the lottery. I am a woman who believe that one day i will win the lottery.finally my dreams came through when i email PRIEST WISDOM  . and tell him i need the lottery numbers. i have come a long way spending money on ticket just to make sure i win. But i never know that winning was so easy until the day i meant the spell caster online which so many people has talked about that he is very great in casting lottery spell, so i decide to give it a try.I contacted this man and he did a spell and he gave me the winning lottery numbers. But believe me when the draws were out i was among winners. i won $1,000,000  Dollar. PRIEST WISDOM truly you are the best, with these man you can win millions of money through lottery. i am so very happy to meet these man, i will forever be grateful Email him Supernaturalspell1@gmail.com or WHATSAPP  or Call Via +2348124644470   BLOGSPOT : https://lotteryspellcaster1.blogspot.com/

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  2. Its a miracle that I am alive today. I encounter HERPES SIMPLEX VIRUS (HSV1/2) for good four (4) years, six (6) months and twelve (12) day with my calculations, before I meet the great Dr. Sambo. I am DEBORAH BALOGH from Fresno California, united state of America and I was affected with herpes virus. Herpes is a viral infection cause by the Herpes simplex virus, marked by painful, watery blister in the skin or mucous membrane or on the genitals. This was what I suffered for good four years. I have visited CVS Pharmacy in Fresno for treatment but no improvement. I meet Dr. Sambo online while I was searching for herpes cure I read a testimony about his work. I give a try that now becomes a testimony in my life. I contacted Dr. Sambo via his E-mail divinespellhome@gmail.com and he did not responds to me in time and I went back to the same testimony for his mobile number and I called him immediately +2348145810121 and he respond to my call. He welcome me as a daughter and I explain my four years situation to him and he said is done just as I have contacted him and I believed in him. Dr. Sambo sends me some herbal medication for herpes cure and he gave me instruction on what to do and I obeyed his instruction. Changes started after three days of applying the herbal medication. I went to the same CVS Pharmacy in Fresno for test and i was herpes negative. I do not know how to thanks Dr. Sambo for saving my life. To God be the Glory, I am living healthy with my family today.Indeed, Dr. Sambo is a great man divinespellhome@gmail.com Dr. Sambo Whats,App.+2348145810121 God bless Dr. Sambo for his good work...

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  3. Its a miracle that I am alive today. I encounter HERPES SIMPLEX VIRUS (HSV1/2) for good four (4) years, six (6) months and twelve (12) day with my calculations, before I meet the great Dr. Sambo. I am DEBORAH BALOGH from Fresno California, united state of America and I was affected with herpes virus. Herpes is a viral infection cause by the Herpes simplex virus, marked by painful, watery blister in the skin or mucous membrane or on the genitals. This was what I suffered for good four years. I have visited CVS Pharmacy in Fresno for treatment but no improvement. I meet Dr. Sambo online while I was searching for herpes cure I read a testimony about his work. I give a try that now becomes a testimony in my life. I contacted Dr. Sambo via his E-mail divinespellhome@gmail.com and he did not responds to me in time and I went back to the same testimony for his mobile number and I called him immediately +2348145810121 and he respond to my call. He welcome me as a daughter and I explain my four years situation to him and he said is done just as I have contacted him and I believed in him. Dr. Sambo sends me some herbal medication for herpes cure and he gave me instruction on what to do and I obeyed his instruction. Changes started after three days of applying the herbal medication. I went to the same CVS Pharmacy in Fresno for test and i was herpes negative. I do not know how to thanks Dr. Sambo for saving my life. To God be the Glory, I am living healthy with my family today.Indeed, Dr. Sambo is a great man divinespellhome@gmail.com Dr. Sambo Whats,App.+2348145810121 God bless Dr. Sambo for his good work...

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  10. Hello Everyone out there,I am here to give my testimony about a Herbalist doctor who helped me . I was infected with HERPES SIMPLEX VIRUS in 2011, i went to many hospitals for cure but there was no solution, so I was thinking how can I get a solution out so that my body can be okay. One day I was in the river side thinking where I can go to get solution. so a lady walked to me telling me why am I so sad and i open up all to her telling her my problem, she told me that she can help me out, she introduce me to a doctor who uses herbal medication to cure HERPES SIMPLEX VIRUS and gave me his email, so i mail him. He told me all the things I need to do and also give me instructions to take, which I followed properly. Before I knew what is happening after two weeks the HERPES SIMPLEX VIRUS that was in my body got vanished . so if you are also heart broken and also need a help, you can also email him at {oliha.miraclemedicine@gmail.com}
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  11. I was haven herpes 2 on my private part. I have had them for about 2 and a bit years. I am so scared what my mates are going to says if there should fined out i have herpes on my private part and due to the virus my girlfriend broke up with me. I have been to the Doctors 9 times to get it treated. They all come back. I have been using Tee Tree Oil and Wartner (You freeze them at home) and they seem to be keeping the smaller herpes small but they can't seem to treat the larger ones. They don't get any bigger, but then they can't shrink as much. They get smaller a little part at a time. At least they are getting smaller! As soon as I see a new herpes appearing, then I treat it. At the moment I have been using Tee Tree twice a week and then using Wartner every 2 weeks. I was wondering if there was any other information about how to get rid of it. I am only a teenager and I hate it most when it get pi-chins me to scratch it, it get sweets when scratching it most times! I want to get rid of it so bad! DR.ONOKUN website has been a huge help and has helped me realize a lot more about me and my family of genital herpes! so that was when i switch for natural remedy to see if there could be any help by herbal remedy, i search and i saw a great posts by Sarah devise adebayo ehijactor and shanttel Merritt on about the great herbal doctor that get them rid of there disease infection. and this great herbal doctor was called DR.ONOKUN so that was when i contacted him for my own treatment and he prepared me some herbs which i takes for some couples of days, and i take it as he says before i am to no me and my family was perfectly cure for it and never experience it again. please friends if you have herpes virus and you really wants to get rid of it, please contact this great DR.ONOKUN for herbal treatment and you will get rid of it. EMAIL. dronokunherbalcure@gmail.com 

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  12. I was haven herpes 2 on my private part. I have had them for about 2 and a bit years. I am so scared what my mates are going to says if there should fined out i have herpes on my private part and due to the virus my girlfriend broke up with me. I have been to the Doctors 9 times to get it treated. They all come back. I have been using Tee Tree Oil and Wartner (You freeze them at home) and they seem to be keeping the smaller herpes small but they can't seem to treat the larger ones. They don't get any bigger, but then they can't shrink as much. They get smaller a little part at a time. At least they are getting smaller! As soon as I see a new herpes appearing, then I treat it. At the moment I have been using Tee Tree twice a week and then using Wartner every 2 weeks. I was wondering if there was any other information about how to get rid of it. I am only a teenager and I hate it most when it get pi-chins me to scratch it, it get sweets when scratching it most times! I want to get rid of it so bad! DR.ONOKUN website has been a huge help and has helped me realize a lot more about me and my family of genital herpes! so that was when i switch for natural remedy to see if there could be any help by herbal remedy, i search and i saw a great posts by Sarah devise adebayo ehijactor and shanttel Merritt on about the great herbal doctor that get them rid of there disease infection. and this great herbal doctor was called DR.ONOKUN so that was when i contacted him for my own treatment and he prepared me some herbs which i takes for some couples of days, and i take it as he says before i am to no me and my family was perfectly cure for it and never experience it again. please friends if you have herpes virus and you really wants to get rid of it, please contact this great DR.ONOKUN for herbal treatment and you will get rid of it. EMAIL. dronokunherbalcure@gmail.com 

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  13. Anonymous9:22 AM

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    ReplyDelete
  14. Anonymous9:22 AM

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