Protein complexity, gene duplicability and gene dispensability in the yeast genome

Abstract

Using functional genomic and protein structural data we studied the effects of protein complexity (here defined as the number of subunit types in a protein) on gene dispensability and gene duplicability. We found that in terms of gene duplicability the major distinction in protein complexity is between hetero-complexes, each of which includes at least two different types of subunits (polypeptides), and homo-complexes, which include monomers and complexes that consist of only subunits of one polypeptide type. However, gene dispensability decreases only gradually as the number of subunit types in a protein complex increases. These observations suggest that the dosage balance hypothesis can explain well gene duplicability of complex proteins, but cannot completely explain the difference in dispensabilities between hetero-complex subunits. It is likely that knocking out a gene coding for a hetero-complex subunit would disrupt the function of the whole complex, so that the deletion effect on fitness would increase with protein complexity. We also found that multi-domain polypeptide genes are less dispensable but more duplicable than single-domain polypeptide genes. Duplicate genes derived from the whole genome duplication event in yeast are more dispensable (except for ribosomal protein genes) than other duplicate genes. Further, we found that subunits of the same protein complex tend to have similar expression levels and similar effects of gene deletion on fitness. Finally, we estimated that in yeast the contribution of duplicate genes to genetic robustness against null mutation is approximately 9%, smaller than previously estimated. In yeast, protein complexity may serve as a better indicator of gene dispensability than do duplicate genes.

Fig. 1

Cumulative fitness distribution of gene deletions of WGD (A, C, E) and non-WGD (B, D, F) duplicate genes for hetero-complexes (A, B), homo-complexes (C, D), and proteins without complex annotation (E, F). Duplicate genes are further subdivided according to the K_A of each gene to its most similar paralogue in the genome. N indicates gene number.

Fig. 2

Fitness distribution of gene deletions after exclusion of duplicate genes. Homo-complexes include monomers, homo-dimers, and homo-multimers. The number in the parentheses for hetero-complexes indicates the number of subunit types. N indicates gene number.

Fig. 3

Fitness distribution of gene deletions for polypeptides subdivided according to their domain annotation after exclusion of duplicate genes. Single-domain polypeptides are, on average, more dispensable than multi-domain polypeptides (proportion of weak effect genes, p < 0.05; proportion of lethal genes, p < 10⁻⁶), while polypeptides with 2 or > 2 domains have similar dispensability (p > 0.1). N indicates gene number.