Mutation is ultimate source of all genetic variation

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Mutation is ultimate source of all genetic
variation
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Other ways populations generate or acquire
genetic variation?

• Gene flow (migration)
• Recombination
• Hybridization
• Horizontal gene transfer

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Mutations in animals

• Germ line mutations
• Somatic mutations
• Which are heritable?

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Mutations single base-pair mutations
Purines Pyrimidines
Transitions Transversions
Synonymous substitution
Non-synonymous subst. (silent)
(replacement) TGT --gt TGC TGT --gt
TGG Cys --gt Cys Cys --gt Trp
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Other silent mutations

• single-base mutations, deletions, or insertions
  within introns
• mutations within other non-coding regions such as
  repetitive DNA and pseudogenes

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However, some noncoding sequences have essential
functions

• promoters
• enhancers
• transcription termination signals
• intron splice junctions
• Mutations in these noncoding regions will have
  phenotypic effects.

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Mutation rates
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Best data from C. elegans

• Accumulated mutations in 72 inbred lines for 400
  generations
• Sequenced 62,000 bp from each line
• 30 mutations
• 13 insertions (1-500 bp)
• 4 deletions (1-66 bp)
• 13 base substitutions (8 transitions
  5 transversions)
• 2.1 mutations per haploid genome per generation
• Denver et al. (2004) Nature 430 679-683.

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Effects of mutations
Proportion of new mutations
0 (neutral)
lethal or sterile
deleterious
beneficial
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Transposable elements

• translocate from one location to another
• can cause deletions, insertions, inversions,
  rearrangements

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Hybrid Dysgenesis

• Sterility and gonad abnormalities in offspring of
  some crosses between different populations of
  Drosophila melanogaster.
• But only in one direction of the cross!

• Mv x P
• Pv x M
• Pv x P
• Mv x M
• dysgenesis normal

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Hybrid dysgenesis is due to TEs called P
elements

• Flies that can produce dysgenesis have these P
  elements, but dysgenesis only occurs when males
  that have these elements are crossed to females
  that dont have them. Eggs from P females
  suppresses transposition.
• P elements spread through natural populations
  starting abut 50 years ago.
• Suppressor of transposition also evolved in these
  pops.

• But many old laboratory populations dont have
  P elements b/c they were established from natural
  populations more than 50 years ago.

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Hybrid Dysgenesis

• Also observed in other organisms
• Mammals (marsupials)
• Plants (rice)
• Probably occurs in other organisms too.

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Are mutations random?

• With respect to selective advantage?
• That is, do mutations arise spontaneously without
  regard to whether or not they are advantageous in
  the current environment? Or, is there a tendency
  for mutations to occur that are advantageous in
  the current environment?

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Lederberg Lederberg (1952)

• Asked whether adaptation arose from a process of
  random mutation followed by selection in a new
  environment, or whether environmental stressors
  directly induce mutations that confer an
  adaptive.
• Knew that if a population of E. coli was exposed
  to antibiotic, most of the bacterial cells would
  die. But, if the original population was large
  enough, it would soon be repopulated with
  bacteria, all of which were resistant to the
  antibiotic.
• Does antiobiotic select for rare pre-existing
  cells that have the resistance mutation, or does
  the antibiotic itself induce the cells to produce
  new mutations that confer resistance?

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Sterile velvet stamp
Master Plate--bacterial colonies on a petri dish
Replica plates on selective media (streptomycin)
Replica plates on non- selective media (no
antibiotic)
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Conclusions

• Mutations arise randomly with respect to
  selective advantage in the current environment.

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Are mutations random?

• With respect to position in the genome?
• No, mutational hotspots exist
• Positions in DNA that mutate more frequently than
  expected (more often than other positions)
• Due to unusual character of those sites
• (e.g. repeated sequences, methylated bases)

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Chromosomal mutations are the source of variation
for chromosomal evolution
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Gene duplications are a source of evolutionary
novelty

• Ribosomal DNA
• Globins (alpha and beta)
• Homeobox genes

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Inversions
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Inversions Suppress Recombination!

• Organisms carrying an inversion tend to undergo
  little crossing over in the inversion region in
  both inversion and non-inversion chromosomes.

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Hybridization introgression
M. musculus
Hybrid zone
M. domesticus
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Horizontal gene transfer

• Species that cannot interbreed should not be able
  to exchange genes
• But, a few cases of transfer of genetic material
  between distantly related species
• Cross-infection by retroviruses (which can
  incorporate host DNA into their genomes) is
  suspected route of gene transfer.

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Virogenes are vertebrate genes that are similar
to, and thought to have arisen from, retroviruses