Mutation examples involving switches. What Darwin never knew (switches) video arwin-never-knew.html.

Mutation examples involving switches

• What Darwin never knew (switches) video• http://www.pbs.org/wgbh/nova/evolution/d

arwin-never-knew.html

• Watch 1:44:00 to 1:49:15

• The work highlighted in the Nova piece on Katie Pollard fits nicely with earlier studies comparing gene expression patterns in human and chimp.

2002: Gene expression differences weren’t that different in non-brain tissues…

Enard et al., Science, 2002, 296: 340-343

Gene activity, not sequence, “makes us human”

2003: Gene expression in human and chimp cerebral cortex …

Caceres et al., 2003, PNAS, 100: 13030-13035

Red = increased expression169 different genes with expression differences between human and chimp in cortexMost genes were more highly expressed in human vs. chimp

Katie Pollard’s work implicates the “switches” as the genetic mechanism behind the gene expression differences

Prx1

Cretekos et al., 2008, Genes and Development

Prx1 is naturally expressed at different levels in bat and mouse during limb development

Created knock-in mice (replaced mouse switch with bat switch for Prx1). Limb length was increased 6% (sig)

• Sean Carroll, “switches” and fly wing spots (gene expression is turned on by particular sequence)

A glimpse of the actual wing trans-regulatory landscape.

Prud'homme B et al. PNAS 2007;104:8605-8612

©2007 by National Academy of Sciences

Prud'homme B et al. PNAS 2007;104:8605-8612

©2007 by National Academy of Sciences

Body-plan evolution by compounding regulatory changes.

Prud'homme B et al. PNAS 2007;104:8605-8612

©2007 by National Academy of Sciences

Schematic comparison of Hoxc8 expression in chicken and mouse in relationship to morphological landmarks.

Belting H et al. PNAS 1998;95:2355-2360

©1998 by The National Academy of Sciences

Hoxc8 figure from Time Mag.

Examples involving gene duplication

• Can arise by unequal crossing over (gene duplication)

• Can arise by genome duplication (failure of meiosis to produce haploid gamete)

Is it common?

• Several hundred duplicated genes every million years in Drosophila

Gene Duplications• Especially important in evolution…

– Can change protein quantity (e.g., human amylase)– Duplicated gene may take on a new job if mutation

alters it– Duplicated gene may be expressed at a different

time or location if “switch” sequence is altered

Marques-Bonet et al., Nature, Feb. 12, 2009

Gene Duplication seems to be more common in our lineage than in other primate lineages

Gene duplication seems especially common in the human lineage even compared to the chimp/bonobo lineage… does this account for gene

expression diffferences we discussed earlier?

Marques-Bonet et al., Nature, Feb. 12, 2009

Color vision is useful…

http://www.neitzvision.com/content/home.html

Color vision in Old World Primates (including humans) is trichromatic

Jacobs and Nathans, Scientific American, April 2009

Red and green genes are very similar and are likely due to a duplication event (unequal crossover) and gene co-option

Jacobs and Nathans, Scientific American, April 2009

Both males and females are trichromatic…

Jacobs and Nathans, Scientific American, April 2009