Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

OVERVIEW OF DEVELOPMENT
1149
Genes Involved in Cell–Cell Communication and Transcriptional
Control Are Especially Important for Animal Development
What are the genes that animals share with one another but not with other kingdoms
of life? These would be expected to include genes required specifically for
animal development but not needed for unicellular existence. Comparison of
animal genomes with the genome of budding yeast—a unicellular eukaryote—
suggests that three classes of genes are especially important for multicellular
organization. The first class includes genes that encode proteins used for cell–cell
adhesion and cell signaling; hundreds of human genes encode signal proteins,
cell-surface receptors, cell adhesion proteins, or ion channels that are either not
present in yeast or present in much smaller numbers. The second class includes
genes encoding proteins that regulate transcription and chromatin structure:
more than 1000 human genes encode transcription regulators, but only about 250
yeast genes do so. As we shall see, the development of animals is dominated by
cell–cell interactions and by differential gene expression. The third class of noncoding
RNAs has a more uncertain status: it includes genes that encode microR-
NAs (miRNAs); there are at least 500 of these in humans. Along with the regulatory
proteins, they play a significant part in controlling gene expression during
animal development, but the full extent of their importance is still unclear. The
loss of individual miRNA genes in C. elegans, where their functions have been well
studied, rarely leads to obvious phenotypes, suggesting that the roles of miRNAs
during animal development are often subtle, serving to fine-tune the developmental
machinery rather than to form its core structures.
Regulatory DNA Seems Largely Responsible for the Differences
Between Animal Species
As discussed in Chapter 7, each gene in a multicellular organism is associated
with many thousands of nucleotides of noncoding DNA that contains regulatory
elements. These regulatory elements determine when, where, and how strongly
the gene is to be expressed, according to the transcription regulators and chromatin
structures that are present in the particular cell (Figure 21–5). Consequently,
a change in the regulatory DNA, even without any change in the coding DNA, can
alter the logic of the gene-regulatory network and change the outcome of development.
As discussed in Chapter 4, when we compare the genomes of different animal
species, we find that evolution has altered the coding and regulatory DNA to
different extents. The coding DNA, for the most part, has been highly conserved,
the noncoding regulatory DNA much less so. It seems that changes in regulatory
DNA are largely responsible for the dramatic differences between one class of
animals and another (see p. 227). We can view the protein products of the coding
sequences as a conserved kit of common molecular parts, and the regulatory
DNA as instructions for assembly: with different instructions, the same kit of parts
can be used to make a whole variety of different body structures. We will return to
this important concept later.
MUSCLE CELL
DNA
transcription
regulators
gene 1 gene 2 gene 3
regulatory modules
DEVELOPMENTAL TIME
transcription
regulators
SKIN CELL
Figure 21–5 Regulatory DNA defines
the gene expression patterns in
development. The genome is the same in
a muscle cell as in a skin cell, but different
genes are active because these cells
express different transcription regulators
that bind to gene regulatory elements. For
example, transcription regulators in skin
cells recognize a regulatory element in
gene 1, leading to its activation, whereas
a different set of regulators is present in
muscle cells, binding to and activating gene
3. Transcriptional regulators that activate
the expression of gene 2 are present in
both cell types.