Evolution, 4th Edition

EvoluTion And dEvEloPmEnT 387

integration” [51]. (The term phenotypic integration is

more frequently used today.) At about the same time, the

Russian geneticist Raissa Berg found that correlations

among flower structures and among vegetative struc-

tures were higher than correlations between floral and

vegetative elements [5]. Such observations led others,

such as the Austrian zoologist Rupert Riedl [60], to pro-

pose that natural selection shapes genetic correlations, so

that functionally interdependent features become more

strongly integrated. Population genetic models by Günter

Wagner and others show that pleiotropic correlations

among characters can be shaped by natural selection, so

that evolvability itself can evolve [15, 26, 53, 83].

We have seen that a transcription factor often binds

to enhancers (cis-regulatory sequences) of diverse genes,

and that the many enhancers that affect transcription of a

gene can bind diverse transcription factors. Gene regula-

tory networks therefore have great potential for extensive

pleiotropy: one TF might affect expression of many genes,

or one gene might be responsive to different TFs in dif-

ferent cells. But there is also great opportunity for speci-

ficity. In mammals, for example, expression of two Hox

genes, Hoxd13 and Hoxa13, is required for development of

both digits and external genitals. The expression of these

genes depends on their enhancers. Some enhancers

enable expression in both digital and genitalic primordia,

while other enhancers govern expression in one or the

other developing structure (FIGURE 15.21).

Pleiotropy can evolve if variation in one gene alters the

effect of another locus on two or more different charac-

ters. For example, a change of a transcription factor could

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Mandible length

A 1 A 2

A 2 A 2

A 1 A 1

Maxilla length

1 4

3 2 FIGURE 15.20 How pleiotropy might facilitate

or constrain evolution. Suppose there is a positive

genetic correlation between two features, such as

the length of the upper and lower parts (maxilla

and mandible, respectively) of a bird’s bill. Usually,

several or many pleiotropic genes will contribute

to the correlation; here only the effects at locus A

are shown. Suppose the ancestral state is short for

both bill parts (1). Often, selection for a longer bill

(arrow pointing up and to the right) will favor both

parts maintaining equal length (perhaps because this

aids in picking up food). Then the positive genetic

correlation enhances the response to selection. But

the positive pleiotropic correlation may prevent

or slow down the response to selection for a long

maxilla and short mandible (arrow pointing up and

left), or for a short maxilla and long mandible (arrow

pointing down and right). The birds shown are the

Hawaiian honeycreepers Hemignathus virens (1), H.

obscurus (2), and H. lucidus (3); the latter two spe-

cies are extinct. Bird 4, the black skimmer (Rynchops

niger), is very distantly related to the honeycreepers.

Skimmers are the only birds with a longer mandible,

which is used for snatching fish as the birds fly above

the water surface.

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II-1 GT2

Prox II-1 + GT2

FIGURE 15.21 Different enhancers of the Hoxd13 gene in mouse

embryos vary in whether or not they are pleiotropic. Blue-green

staining shows sites of Hoxd13 expression in transgenic embryos

with the II-1, GT2, or Prox enhancer, or with a combination of II-1

and GT2. In each panel, the entire embryo is shown on the left and

close-ups of the digits (above) and the genital tubercle (below) are

on the right. The Prox enhancer causes the gene to act pleiotropi-

cally: it is expressed in both digits and the genital tubercle. Without

Prox, enhancers II-1 and GT2 cause gene expression only in the

digits or the genital tubercle, respectively. Neither of the latter en-

hancers is pleiotropic; without Prox, both Il-1 and GT2 are needed

to express Hoxd13 in both sites (Il-1 + GT2). (From [38].)

15_EVOL4E_CH15.indd 387 3/22/17 1:30 PM