The basic thesis of Your Inner Fish is that we can learn something about ourselves by studying other organisms and observing the similarities between us. Chapter 2 examines the anatomy of the limbs of a number of different organisms. That chapter began with the observations of Sir Richard Owens who saw how many diverse organisms shared a common body plan, as exemplified by the structure of the limbs.

Darwin explained these similarities by proposing that the source of this commonality was that there exists a real relationship between even apparently diverse species. If this hypothesis is correct, we can expect that more similarities can be found and that these comparisons go well beyond skin deep.

Chapter 3 expands on this theme, retaining the focus on limb / hand construction and moving from simple anatomical comparisons to the underlying genetics that control the development of these structures.

If you study genetics for long you will see patterns in the way that genes work together. There often exists a number of genes responsible for some specific structure that are all controlled by a more limited number of regulator genes, these too are controlled by some master regulator. The master regulator often acts as a toggle switch that turns on or off certain other genes in a system leading to a cascade of effects. Possibly even more interesting is that these same master regulator genes may be found again and again initiating different outcomes in different locations.

In the case of the ZPA, it was found that this patch of tissue secretes a substance that provides a gradient across the developing limb leading to differential developmental patterning in digits according to the dose of hormone cells receive.  This effect was most clearly demonstrated by inserting a second ZPA in a fashion that creates a mirror image gradient, leading to a corresponding mirror image limb structure  (see below.)

Shubin describes one of these regulatory pathways as being controlled by a patch of tissue called the zone of polarizing activity (ZPA). This patch controls the development of limbs by providing chemical cues to cells in the area. Later, the chemical entity that is secreted from the ZPA and controls this behavior was identified and named Hedgehog / Sonic Hedgehog.  Further experiments have been performed using variable quantities of Sonic Hedgehog or modified hormone resulting in similar malformations of limbs.

One trick that Shubin highlights several times throughout Your Inner Fish is how genes or proteins from one animal may be swapped into another animal and work perfectly normally. The reason he likes to point out the success of these experiments is that that provide excellent support for his hypothesis that all life is related.

An alignment of Sonic Hedgehog proteins is presented below to illustrate the similarities across a number of species. Each organisms’ primary amino acid sequence is presented stacked upon other organisms’ sequences. Identical amino acids are highlighted in yellow.