Homogeneity and heterogeneity of functional element composition of genome units across human and seven model organisms

Abstract

Is a chromosome a miniature of its genome, with the same mix of functional elements as the whole? We ask this of eight annotated genomes: human, mouse, zebrafish, Caenorhabditis elegans, Drosophila melanogaster, Saccharomyces cerevisiae, Arabidopsis thaliana and maize. Elements are classified in a four-level hierarchy, from five major classes (protein-coding genes, ncRNA genes, transposable elements (TEs), pseudogenes, IG/TR gene segments) down to finer classes. Units are chromosomes or arms, cytogenetic bands, equal cuts of each chromosome, and random segments of matching size. We compare each unit with the genome and with other units, call compositions homogeneous when they differ by less than 5%, and score each against a random sample of the same size. The first finding is a surprising homogeneity. The level-1 compositions of the major chromosomes match each other and the genome in maize, zebrafish, yeast and C. elegans, and in fly down to the major arms. Finer classes can be homogeneous too: protein function in Arabidopsis, and the Wicker TE orders in maize. Enzyme reaction classes are interchangeable between chromosomes in all eight genomes. The second finding is a structured heterogeneity. Where a unit departs from its genome, it does so in one of three ways: clusters of named elements, such as rRNA genes or immune receptor loci; megabase-scale compartments, such as TE-rich pericentromeric heterochromatin; and lineage-specific gene families, visible only at the finest levels. Corrected for chance, the genomes fall into groups. For protein function and gene families, composition is more uniform in plants and fly than in vertebrates, and least uniform in C. elegans. For the major classes and TE orders, uniformity follows where each genome places its repeats, along the arms (maize, zebrafish) or around the centromeres (Arabidopsis, fly), not its lineage.