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 viruss 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 youve
discussed DNA replication. Alternatively, you may wish to incorporate this material after youve 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

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.