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How did viruses originate?

“Viral Mutation Evolved”Media: Pastel on paperWALTER DUPRIEST  acanthusarts.org  

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• Virus first hypothesis– Originated before cells

• Viruses from all three domains have similar characteristics

• Predate LUCA

LUCA

Original virus prebiotic RNA molecule

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• Escape hypothesis– Fragments of escaped genome

• Bacteriophages originated in the prokaryotic genome

– Derived from an autonomously replicated plasmid

• Eukaryotic viruses originated from the eukaryotic genome

• Archaean viruses originated from the Archaean genome

– DNA developed from RNA viruses

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OriginalRNA organism

RNA viruses

DNA viruses

DNA is more stableLess prone to mutationsLarger more complex proteinsProtection against enzymes that degrade RNA

Viral DNA become incorporated into cellsDNA genes had a selective advantage

Did DNA organisms evolve 3 separate times or just once?

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• Regressive hypothesis– Reduction of a parasite

• Facultative parasite become dependent upon the host

• Evolved towards an obligate parasite / host relationship

• Similar to the reduction of endosymbiont to the mitochondria and photosynthesis

• Parasite looses genes and become more dependent upon the host

– Rickettsia like organism Chlamydia like organisms Pox like virus

Prangishvili et al. Viruses of the Archaea: a unifying view. Nature Reviews Microbiology 4:837-848.

The Biology of Viruses (2nd ed.) by Voyles. McGraw-Hill Co., Inc.

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Rickettsia

Pox virusds DNA100 genes

ChlamydiaNo cell wall0.3 and 1.0 m in diameter

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MimivirusA unique virus

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• Pathogen of amoebae – Acanthamoeba polyphaga – Microbiologists observed a

Gram + coccus within the amoeba

• Large virus– Diameter of capsid is 400

nm– 80 nm fibrils

• Nucleocytoplasmic Large DNA virus– NCLDV

MimivirusMimicking microbe

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Gram stain

Electron micrograph

ASM News 71(6):278-284

TEM images

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Mimivirus400 nm = 0.4 m

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• Linear ds DNA • Approx 1.2 million bp

– Largest viral genome– Larger genome than 20 prokaryotic organisms

• 1262 open reading frames– Putative genes

• Contains 21 genes that are found in all NCLDV• Contains metabolic genes not found in any

other virus– Contains genes for nucleotide synthesis,

protein synthesis, DNA repair, polysaccharide synthesis genes

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There are 7 minivirus genes that are present in Eukaraya, Bacteria, and Archaea.

A DNA sequence analysis places mimivirus closest to the Eukaraya in the 3 domain system

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Mimivirus is hypothesized to be the ancestor of a virus which contained more eukaryotic genes

15Raoult 2005 ASM News 71(6):278-284

Mimiviruses are an exception that provide evolutionary clues to the origin of life

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Proteinaceous Infectious AgentsTransmissible Spongiform Encephalopathies

• Prions • Normal proteins that become misfolded in

the mammalian brain• PrP

• Spongiform encephalopathies • Holes in the brain

• Human diseases• Creutzfeldt-Jakob Disease• New variant CJD• Kuru• Gerstmann-Straussler-Scheinker Syndrome • Fatal Familial Insomnia

• Several animal diseases• Scrapie in sheep & goats• Bovine spongiform encephalopathies (BSE)• Chronic wasting in elk and mule deer• Similar diseases in cat & mink

Dementia; early neurologic signs

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• Originally thought to be a viral disease• No RNA or DNA has been isolated• Treatment with UV did not reduce

virulence

• Prions have been produced in yeast cells

• Useful experimental model

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• Amino acid sequence can fold into two different structures– Cellular PrP PrPc

– Prion PrP PrPsc

• Prion Prp can cause a conformational change in the shape of the cellular PrP

• Ingesting the prion PrP can cause cellular PrP to convert to disease causing form

• Prion PrP are not denatured by…– Cooking– UV irradiation– Degradative enzymes

Stanley B. PrusinerThe Nobel Prize in Physiology or Medicine 1997

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Cellular PrP PrPc Prion PrP PrPsc

helicesPleated sheets

22nobelprize.org

the PrPsc accumulates primarily in the cerebral cortex

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How does PrPsc arise?• Horizontal transmission from

consuming contaminated food or animal feed– Sheep to a cow

• Veritcal transmission– Mutations in the wildtype prion gene

are transmitted from parent to child• Spontaneously

– Approximately 1 in a million humans develop CJD disease

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• Creutzfeldt-Jakob disease (CJD)– 1920’s– 1 in a million individuals

• Mutations in the human PrP gene produced the first prion PrP

• CJD is inherited– Families of Ashkenazi Jews – Median age of onset is 68 years– Median length of disease 5 months

• Kuru– Papua New Guinea– Cannibalism

nobelprize.org

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• European BSE– Meat and bone meal from sheep were

commonly added to animal feed as a protein supplement

• Scrapie-infected• 1980’s

– Healthy cattle consumed the PrPsc protein– Developed BSE

• 1990’s– Approximately 100 individuals in the U.K. and

France contracted the new variant CJD• Median age of onset is 28• Median length of disease is 14 months• Prominent psychiatric/behavioral symptoms; painful

dyesthesiasis; delayed neurologic signs – Unpleasant sensations that are produced in response to

normal stimuli– Painful tingling, burning and numbness

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BSE in the USA

• December 2003– An adult Holstein cow from

Washington State– The BSE infected cow was imported

from Canada in August 2001

• 2004– A single BSE American cow

• March 2006– A single BSE American cow

28www.cdc.gov

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Viroids

• Smallest known pathogens

• Naked ss RNA molecules with no protein

• ~ 246-399 nucleotides

• No protein encoding genes!

• Only known to infect plants (e.g., potato spindle tuber viroid, citrus exocortis viroid)

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Viroids (Continued)

• Infection can be symptomless or severe in symptoms, even lethal

• Severe syptoms tend to be growth related suggesting that viroid is a form of “regulatory RNA” that “rebelled”

• None known in animals or prokaryotes as yet

• Single-stranded but may appear to be ds based on secondary structure