14.4 The Cell Cycle

189

Differences Between Prokaryotes and Eukaryotes (3)

The above considerations do not directly address the question of why prokaryotes

have rather compact genomes; they seem to be limited to about 10 million base

pairs (10 Mb) (and many bacteria living practically as symbionts in a highly con-

strained environment manage with far less). In a general sense, one can understand

that prokaryotes are under pressure to keep their genomes as small as practicable;

they are usually replicating rapidly under rr-selection (Sect. 14.9.4) and the need to

copy 1000 million base pairs would be physicochemically incompatible with a short

interval from generation to generation. On the other hand, most of the cells in a

metazoan are not replicating at all, and the burden of copying enormous genomes

during development is perhaps compensated for by the availability of plenty of raw

material for exploratory intraorganismal gene development (which the prokaryotes

do not need because of the facility with which they can acquire new genetic material

from congeners).

It has recently been shown that the nature of gene regulation also imposes certain

constraints on the relationship between the amounts of DNA assigned to coding (for

proteins) and those which are considered to be noncoding (i.e., corresponding to

regulatory sites such as promoters). According to what is known about the molecular

details of gene transcription (Sect. 14.8.2), to a first approximation each gene (with

an average length of about 300 base pairs) requires a promoter site (which might

have of the order of 10 base pairs). This gives 9:1 as the typical ratio of “coding” to

“noncoding” DNA in prokaryotes. ²⁸ In the spirit of Wright’s “many to many” model

of regulation, gene regulatory networks are expected to be of the “accelerated growth”

type (see Sect. 12.2), because each new gene that is added should be regulatorily

connected to a fixed fraction German rr of the existing genes. Hence, if gg is the number of

genes, then the number of regulations (edges of the graph)r equals German r g squaredr = rg². These regulations

are themselves mediated by proteins (the transcription factors) encoded by genes.

However, there is an upper limit to the number of interactions in which a protein can

participate, roughly fixed by the number of possible binding sites on a protein and

their variety; empirical studies ²⁹ suggest that the upper limitk Subscript normal m normal a normal xkmax of the degreekk of the

network is about 14. Since k equals 2 r divided by gk = 2r/g, this suggests g Subscript normal m normal a normal x Baseline equals k Subscript normal m normal a normal x Baseline divided by left parenthesis 2 German r right parenthesisgmax = kmax/(2r), which would

appear to correspond to the 10 Superscript 710⁷ base pairs maximum genome size of prokaryotes.

As is well known, however, even allowing for possible overstatement in eukaryotic

genome length, far larger eukaryotic genomes are known to occur. Given their evident

regulatory success (as evinced by the real increase in organismal complexity), one

may suppose that the “accelerated growth” network model still holds; that is, all

of the additional proteins are properly regulatorily integrated. Ahnert et al. (2008)

have proposed that the regulatory deficit implied byg greater than g Subscript normal m normal a normal xg > gmax is met by “noncoding”

RNA-based regulation (see Sect. 14.8.4), the overhead of which is much smaller

28 Some groups of genes, typically those related functionally (such as successive enzymes in a

metabolic pathway), are organized into “operons” controlled by a single promoter site and are

therefore transcribed together.

29 Kim et al. (2006).