Transcript DNA replication - Understanding Evolution

Evolution connection: DNA replication
Learning goals:
Students will understand that 1) molecular mechanisms that preserve the fidelity of the genetic sequence have
been favored by natural selection, 2) some entities, such as HIV, lack some of these mechanisms and so have a
higher rate of mutation and evolution, and 3) many challenges posed to medical science by HIV can be attributed
to the virus’s rapid evolution.
For the instructor:
This short slide set explains molecular features of DNA replication, such as the proof-reading ability of DNA
polymerase, using evolutionary theory and explores an alternate evolutionary scenario (with implications for
human health) in which mutation rates are higher. To integrate it best, use this slide set immediately after you’ve
discussed DNA replication. Alternatively, you may wish to incorporate this material after you’ve covered the topic
of mutation. To save time, you may wish to condense the material on slides two through five by simply listing the
mechanisms and selecting one image to include.
Each of the following slides comes with a sample script for the instructor. To review this script, download the
PowerPoint file and view the Notes associated with each slide.
Evolution Connection slideshows are provided by Understanding Evolution (understandingevolution.org) and are
copyright 2011 by The University of California Museum of Paleontology, Berkeley, and the Regents of the
University of California. Feel free to use and modify this presentation for educational purposes.
Evolution connection: DNA replication
Many mechanisms that help cells avoid mutations have evolved
• Base-pairing specificity
Evolution connection: DNA replication
Many mechanisms that help cells avoid mutations have evolved
• Base-pairing specificity
• DNA polymerase proofreading
Evolution connection: DNA replication
Many mechanisms that help cells avoid mutations have evolved
• Base-pairing specificity
• DNA polymerase proofreading
• Mismatch repair
Evolution connection: DNA replication
Many mechanisms that help cells avoid mutations have evolved
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Base-pairing specificity
DNA polymerase proofreading
Mismatch repair
Excision repair and more
After all these corrections,
mistakes are rare: 1 in 30
million base pairs.
Evolution connection: DNA replication
On average, mutations decrease fitness . . . but there are exceptions.
Mutations maintain genetic variation in populations.
Evolution connection: DNA replication
What happens when proof-reading and repair mechanisms are
missing?
Evolution connection: DNA replication
What happens when proof-reading and repair mechanisms are
missing?
Reverse transcriptase: sloppy copying
(one mistake per thousand base pairs) 
high mutation rate  quick evolution
DNA polymerase: accurate copying (one
mistake per billion base pairs)  low
mutation rate  slow evolution
Molecule images © 2012 David Goodsell & RCSB Protein Data Bank
Evolution connection: DNA replication
The evolutionary trade-off of high-fidelity copying
Evolution connection: DNA replication
HIV evolves quickly
• HIV evades our immune system
• HIV evolves resistance to our
antiviral drugs
• High level of genetic variation
challenges vaccine development
Reprinted by permission from Macmillan Publishers Ltd: Wagner, A. Neutralism and
selectionism: a network-based reconciliation. Nature Reviews Genetics 9, 965-974,
copyright (2008)
Evolution connection: DNA replication
Nowak, M. (1990). HIV mutation rate. Nature. 347:522.
Shankarappa, R. Margolick, J. B., Gange, S. J., Rodrigo, A. G., Upchurch, D., . . .
Mullins, J. I. (1999). Consistent viral evolutionary changes associated with the
progression of Human Immunodeficiency Virus Type 1 infection. Journal of
Virology. 73: 10489-10502.
Xue, Y., Wang, Q., Long, Q., Ng, B. L., Swedlow, H., Burton, J. . . . Tyler-Smith, C.
(2009). Human Y chromosome base-substitution mutation rate measured by
direct sequencing in a deep-rooting pedigree. Current Biology. 19: 1453-1457.