Correlations between Quantitative Measures of Genome Evolution, Expression and Function

Abstract

addition to multiple, complete genome sequences, genome-wide data on biological prop properties of genes, such as knockout effect, expression levels, protein-protein interactions, and others, are rapidly accumulating. Numerous attempts were made by many groups to The questions addressed pertain to the most fundamental aspects of biology: what determines the effect of the knockout of a given gene on the phenotype (in particular, is it essential or not) and the rate of a gene’s evolution and how are the phenotypic properties and evolution con- nected? Many significant correlations were detected, e.g., positive correlation between the ten- dency of a gene to be lost during evolution and sequence evolution rate, and negative correla- tions between each of the above measures of evolutionary variability and expression level or the phenotypic effect of gene knockout. However, most of these correlations are relatively weak and explain a small fraction of the variation present in the data. We propose that the majority of the relationships between the phenotypic (“input”) and evolutionary (“output”) variables can be described with a single, composite variable, the gene’s “social status in the genomic community”, which reflects the biological role of the gene and its mode of evolution. “High-status” genes, involved in house-keeping processes, are more likely to be higher and broader expressed, to have more interaction partners, and to produce lethal or severely im- paired knockout mutants. These genes also tend to evolve slower and are less prone to gene loss across various taxonomic groups. “Low-status” genes are expected to be weakly expressed, have fewer interaction partners, and exhibit narrower (and less coherent) phyletic distribution. On average, these genes evolve faster and are more often lost during evolution than high-status genes. The “gene status” notion may serve as a generator of null hypotheses regarding the connections between phenotypic and evolutionary parameters associated with genes. Any de- viation from the expected pattern calls for attention—to the quality of the data, the nature of the analyzed relationship, or both. Quantitative genomics involves numerous measures reflecting different aspects of the evo- lutionary history and the physiological role of a given gene (protein). One can estimate the evolution rate of a gene, measured in different organisms; its expression level in different tissues and in different taxonomic groups; the tendency of a gene to be lost during evolution of differ- ent lineages of organisms or its tendency to produce paralogous copies via duplication; its *Eugene V. Koonin—National Center for Biote