284

18

Transcriptomics and Proteomics

Another approach is to search for global parameters characterizing the proteome.

Considering it as “vocabulary” transferring information from genotype to phenotype,

it has been found that the distribution of protein abundances p Subscript rpr follows the same

canonical law as the frequency of words in literary texts: ¹⁸

p Subscript r Baseline equals upper P left parenthesis r plus rho right parenthesis Superscript negative 1 divided by theta Baseline comma r equals 1 comma 2 comma ellipsis comma upper Rpr = P(r + ρ)^−1/θ,r = 1, 2, . . . , R

(18.5)

where the two parameters are the informational temperature thetaθ, which is low for

limited expression of the potential gene repertoire and high for extensive expression,

and the effective redundancy rhoρ, which is high when many alternative pathways are

active, and low otherwise. upper RR is the total number of proteins that can be synthesized

in the cell and upper PP is a normalizing coefficient chosen such that the p Subscript rpr sum to unity;

they are ordered according to decreasing magnitude and rr is the rank in this list.

Equation (18.5) is well suited to following the evolution of, for example, a syn-

chronized culture of cells: the parameters are determined for each epoch sampled.

The spatially differentiated expression of proteins is much more difficult to follow

experimentally. The most effective technique is probably time of flight secondary

ion mass spectrometry (Tof-SIMS): secondary ions are sputtered from the sample

by a primary ion gun firing, typically, gallium or oxygen ions. The secondary ions

are extracted into the flight tube of a mass spectrometer and quantified. ¹⁹ One use-

ful way to exploit this technology is to feed the organism under investigation with

isotopically labelled food (Superscript 15¹⁵N is a popular choice since it is not radioactive and the

slight difference in mass from the naturally far more abundant Superscript 14¹⁴N is likely to have

a negligible physiological effect). Any molecules containing Superscript 15¹⁵N will give a clear

signature in the mass spectrometer. The spatial resolution is determined, inter alia

by the fineness of the collimated primary ion beam.

18.7

The Kinome

One of the most fundamental mechanisms for reversible enzyme activation is phos-

phorylation. This reaction is catalysed by enzymes generically called kinases. Several

hundred human kinases are known; collectively they comprise the kinome. Most com-

monly, serine or threonine residues are phosphorylated, but also tyrosine, histidine,

and others are known. The so-called mitogen-activated protein kinases (MAPK),

including MAPK kinases (MAPKK) and MAPKK kinases, comprise perhaps the

best known family. ²⁰ Phosphorylation introduces a bulky, negatively charged (at

neutral pH) group into the amino acid. These changes in both the size and the charge

of the residue typically induce significant conformational changes in the protein;

it is easy to understand in these general terms how phosphorylation of an enzyme

18 See Ramsden and Vohradský (1998) and Vohradský and Ramsden (2001).

19 Fearn (2015).

20 See, e.g., Kolch et al. (2002).