Mutation examples involving switches What Darwin never knew

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… Gene activity, not sequence, “makes us human” Enard et al. , Science, 2002, 296: 340 -343

2003: Gene expression in human and chimp cerebral cortex … Red = increased expression 169 different genes with expression differences between human and chimp in cortex Most genes were more highly expressed in human vs. chimp Caceres et al. , 2003, PNAS, 100: 13030 -13035

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

Prx 1 is naturally expressed at different levels in bat and mouse during limb development Created knock-in mice (replaced mouse switch with bat switch for Prx 1). Limb length was increased 6% (sig) Cretekos et al. , 2008, Genes and Development

• 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 Hoxc 8 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

Hoxc 8 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

Gene Duplication seems to be more common in our lineage than in other primate lineages Marques-Bonet et al. , Nature, Feb. 12, 2009

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 cooption Jacobs and Nathans, Scientific American, April 2009

Both males and females are trichromatic… Jacobs and Nathans, Scientific American, April 2009