BIOLOGY 3301 Evolution Chapter 1

The virus and the whale: how scientists study evolution  
  1. Biological evolution
    • Biological evolution is the process by which inherited traits of a population change over time.
    • Any change in the inherited traits of a population that occurs from one generation to the next
  2. Evolution explains the diversity of life
  3. Understanding evolution has practical implications.
    1. How do pathogens become drug resistant?
    2. What is the source of new pathogens?
Outdoor photograph of an older man with thinning white hair, dressed in a suit.
Theodosius Dobzhansky January 24, 1900 - December 18, 1975
'Nothing in Biology Makes Sense Except in the Light of Evolution'
The American Biology Teacher, March 1973 (35:125-129)

Evolution case studies 2 --Viruses: the deadly escape artists (p. 16)

  • Populations of viruses evolve rapidly in part due to their amazing reproductive potential, and in part due to the ability of different strains to combine their genetic material.

Flu Virus

Structure of influenza, showing neuraminidase marked as NA and hemagglutinin as HA.
Image from Wikipedia

  1. Influenza Outbreaks
    1. Evolutionary biologists help solve the mystery of their appearance
    2. 2009, H1N1 Flu Outbreak (1st edition)
      1. Spread worldwide in a matter of weeks
      2. First noticed in Mexico
      3. 16,000 deaths in U.S.
    3. 2013, H7N9: a new strain of flu infects humans (Fig. 1.16)
    4. 2014, H3N2
  2. Structure of the Influenza virus (Fig 1.17)
    1. the Influenza A virus is responsible for annual flu epidemics and pandemics
    2. Influenza virus is a retrovirus with a genome of 8 RNA strands
    3. The viral RNA genome, consists of 10 genes coding for 10 proteins
      1. Polymerases, structural proteins, surface proteins
      2. The two major surface proteins are neuraminidase and hemagglutinin.
    4. .The genome is carried on eight separate pieces of RNA that can reassort during viral infection (Fig. 1.22)
    5. Retrovirus (HIV) life cycle VIDEO from HHMI
  3. Flu life cycle (Fig. 1.18)   
    1.  virion stage (extracellular, active particle) encounters a host cell
    2. The virion invades a host cell by binding to the cell's surface using hemagglutinin
    3. Virion spills its contents (RNA and 3 proteins: reverse transcriptase, integrase, and protease) into host cell
    4. Reverse transcriptase synthesizes Influenza DNA
    5. Integrase splices Influenza DNA into host's DNA
    6. The host cell's RNA polymerase transcribes the viral genome into messenger RNA
    7. the host cell's ribosomes transcribe the viral mRNA into precursor proteins
    8. Influenza protease cleaves the precursors, yielding mature viral proteins
    9. New virions assemble in the host cell's cytoplasm
    10. New virions bud from the host cell's membrane.
  4. Vaccine design .
    1. Hemagglutinin is the main target of our immune system.
    2. Amino acid sites in hemagglutinin that our immune system recognizes (and remembers) are called antigenic sites. (1st edition).
    3. Antigens in vaccine prime immune system
  5. Understanding evolution has practical implications
    1. How do pathogens become drug resistant?
    2. What is the source of new pathogens?
  6. Why do new flu vaccines need to be made each year? 
    1. Mutations may be harmful or beneficial (Fig. 1.19)
    2. Reverse transcription and mutation rate
  7. Viral strains with beneficial mutations increase in frequency through natural selection (Fig. 1.20)
    1. Viral strain no longer recognized by immune system
    2. Requires new vaccine
    devastating consequences (Fig. 1.21)
    1. Immune system cannot recognize distinct surface proteins
    2. New strains can cause significant mortality: Spanish flu (1918), Asian Flu (1957-58), and Hong Kong Flu (1968-69)
  8. The 2009 outbreak was the result of reassortment (Fig. 1.23)
  9. Molecular clock suggests virus went undetected for months
    1. May not have originated in Mexico (Fig. 1.22)

14.1 Evolving Pathogens from Herron and Freeman

  1. Pathogens have evolved in response to the selection pressures imposed by medicine.there is strong selection imposed by host's immune system for parasites that can evade detection.
  2. The evolution of flu viruses
    1. the Influenza A virus is responsible for annual flu epidemics and pandemics
    2. Influenza virus is a retrovirus with a genome of 8 RNA strands
    3. The strands can reassort
  3. The evolution of antigenic sites
    1. Hemagglutinin is the main target of our immune system.
  4. Flu Virus Evolution
    1. New genes through reassortment
    2. New alleles through mutation
  5. A phylogenetic analysis of frozen flu samples
    1. Figure 14.5a: The molecular evolution of Influenza A hemagglutinin gene over a 20-year period
  6. Flu Virus Evolution
    1. Since flu is an RNA virus, mutation frequency is higher than for a DNA virus
    2. Most strains represented extinct side branches on the phylogeny (Fig. 14.5b)
  7. Knowledge of Flu Evolution & Vaccines
    1. successful strain would have had more mutations in its antigenic versus non-antigenic sites (Fitch et al)
    2. Over 75% of the amino acid replacements in surviving lineages were in antigenic (hemagglutinin) sites (versus <50% in extinct).
  8. A typical pattern observed in most protein coding genes
    1. Evidence for the neutral model
      1. "silent" substitution rates are higher than "replacement" substitution rates.
      2. Fig. 7.21: Among 331 mutations observed in hemagglutinin Influenza A alleles: 58% were silent, 42% were replacement
  9. Evidence for positive selection among the 331 mutations in the hemagglutinin alleles
    1. positive selection occurs when the rate of replacement substitution exceeds the rate of silent substitution.
    2. positive selection is attributed to the action of selection favoring amino acid replacements.
    3. in Influenza A, there are 18 hemagglutin codons exhibiting higher ratios of silent to replacement mutations
    4. These 18 codons are in antigenic sites
    5. this allows us to predict surviving strains and thus make flu vaccines
  10. Positive selection in the hemagglutinin gene
    1. Figure 14.6 Predicting which lineages of flu will survive to cause future epidemics
      1. Usually, it is the lineage with the most amino-acid replacements in its hemagglutinin antigenic sites (indicated by colored dots). Redrawn from Bush (2001).
  11. Origins of pandemic flu strains
    1. If a host becomes infected with two different flu strains these strains could swap RNA strands
    2. Figure 14.7 A phylogeny of flu viruses based on the nucleoprotein gene (important for host recognition).
      1. for each viral strain shows the host species from which it was isolated, the year, and the type of hemagglutinin and neuraminidase it carries.
      2. Codes show that they have different neuraminidases and hemagglutins
  12. Are viruses 'swapping' genes?
    1. Novel Hemagglutinin often associated with pandemics
    2. Prior to the pandemic of 1968, no H3 hemagglutins were ever observed in human flu strains
  13. Origin of Pandemic Flu Strains
    1. Flu strains 'swap' chromosomes
    2. 14.8 A phylogeny of flu virus hemagluttinin genes
    3. Some recent work on Influenza A: recreating the 1918 Spanish Flu virus Ghedin et al. 2005; Taubenberger et al. 2005)



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