Functional Constraint and Molecular Evolution

Abstract

While having one or more specific functions, macromolecules have collective functions (e.g. Donnan equilibrium and aggregation pressure), and general functions (e.g. contribution to organism weight). Successful molecular evolution requires an appropriate balance between the constraints on these functions, which arise from selective pressures acting at the levels of conventional phenotypes (natural selection) and genome phenotypes (reprotypic selection). Genome‐wide constraints include fold pressure (nucleic acid stem‐loop extrusion pressure) and GC‐pressure (the pressure for a certain base composition). When these bring about within‐genome reprotypic selection (hybrid sterility), there is the potential for new species to emerge (speciation). Local constraints include protein pressure (the pressure to encode a protein) and purine‐loading pressure (purine‐rich messenger ribonucleic acid (mRNA) synonymous strands). As more pressures are identified, arguments for neutral evolution weaken.

Key Concepts:

  • Molecules have specific, collective and general functions.

  • Most macromolecules function by virtue of their higher ordered structure.

  • Nucleic acids have both structural and templating functions.

  • Each species achieves its own balance between the competing demands (constraints) of external and internal environments.

  • The organismal phenotype comprises the classical phenotype and the genome phenotype.

  • Natural selection operates on the classical phenotype.

  • Reprotypic selection operates on the genome phenotype.

  • By balancing natural and reprotypic selection mechanisms, the ‘hand of nature’ resolves conflicts between functions.

Keywords: conflict resolution; degenerate code; GC rule; neutralism; purine‐loading; speciation

Figure 1.

Distribution of purine‐loading among biological species. Purine‐loading of coding regions was calculated from codon usage tables for all species represented in the August 1999 release of the GenBank database by more than three genes or more than 2500 bases. The purine‐loading index (bases kb−1) for a particular species was calculated as the sum of 1000((G–C)/N) and 1000((A–T)/N), where G, C, A and T correspond to the number of individual bases, and N corresponds to the total number of bases, in the codon usage table. This measure of the purine‐loading of RNAs disregards 5′ and 3′ noncoding sequences, including poly(A) tails. The value for all human genes (excluding mitochondria) is 42 Kb−1, meaning that, on average, there are 42 more purines than pyrimidines for every kilobase of coding sequence. The shoulder with negative purine‐loading values (i.e. pyrimidine‐loading) corresponds mainly to mitochondrial genes.

Figure 2.

Szybalski's transcription direction rule evaluated as ‘Chargaff differences’ (deviations from Chargaff's second parity rule). Heavy horizontal arrows refer to the ‘top’ and ‘bottom’ strands of duplex DNA. Grey boxes refer to intergenic DNA. Green circles represent RNA polymerases with red arrows indicating the direction of transcription. In the case of leftward transcription the Chargaff difference for the top strand is in favour of pyrimidines (Y). In the case of rightward transcription the Chargaff difference for the top strand is in favour of purines (R). RNAs tend to locate purines as clusters in the loop regions of their secondary structure.

Figure 3.

Summary of potentially conflicting evolutionary pressures as manifest at the level of mRNA (purple line with arrowhead). Boxes indicate the domains over which different pressures operate. (1) (G+C)% pressure (‘GC pressure’) acting primarily at the genomic level, and secondarily affecting mRNA base composition. (2) Fold (stem–loop) pressure acting primarily at the genomic level and secondarily affecting mRNA base order and composition. (3) Purine‐loading pressure acting primarily at the cytoplasmic level to enrich loops with purines. (4) Protein‐encoding pressure derived from environmental interactions (natural selection) relating to specific, collective and general protein functions, which result in base changes in the protein‐encoding part of the mRNA. (5) Regulatory pressures (small lilac boxes) acting primarily at the cytoplasmic level, which result in base changes mainly in the 5′ and 3′ noncoding regions.

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Further Reading

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Forsdyke, Donald R(Jul 2012) Functional Constraint and Molecular Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001804.pub3]