Abstract
How does the information in the genome program the functions of the wide variety of cells in the body? While the development of biological organisms appears to follow an explicit set of genomic instructions to generate the same outcome each time, many biological mechanisms harness molecular noise to produce variable outcomes. Non-deterministic variation is frequently observed in the diversification of cell surface molecules that give cells their functional properties, and is observed across eukaryotic clades, from single-celled protozoans to mammals. This is particularly evident in immune systems, where random recombination produces millions of antibodies from only a few genes; in nervous systems, where stochastic mechanisms vary the sensory receptors and synaptic matching molecules produced by different neurons; and in microbial antigenic variation. These systems employ overlapping molecular strategies including allelic exclusion, gene silencing by constitutive heterochromatin, targeted double-strand breaks, and competition for limiting enhancers. Here, we describe and compare five stochastic molecular mechanisms that produce variety in pathogen coat proteins and in the cell surface receptors of animal immune and neuronal cells, with an emphasis on the utility of non-deterministic variation.
Highlights
Despite the shocking complexity of eukaryotic life, eukaryotic genomes often contain less than 20,000 protein-coding genes
The successful and abundant translation of an olfactory receptor (OR) leads to downstream signaling that turns off important translation-initiation factors, ceasing translation of most other ORs while inducing expression of adenylyl cyclase type 3 (ADCY3), a molecule that is essential for odor signaling (Ron and Walter, 2007; Wang S.-Z. et al, 2012; Dalton et al, 2013)
The selected allele in these systems is found in accessible euchromatic regions, which for antigen receptors is in the nuclear center, for ORs entails the active gene escaping the repressive foci, and for variable surface glycoproteins (VSGs) genes requires the single active expression site to localize to the expression body
Summary
Non-deterministic variation is frequently observed in the diversification of cell surface molecules that give cells their functional properties, and is observed across eukaryotic clades, from single-celled protozoans to mammals. This is evident in immune systems, where random recombination produces millions of antibodies from only a few genes; in nervous systems, where stochastic mechanisms vary the sensory receptors and synaptic matching molecules produced by different neurons; and in microbial antigenic variation.
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