Quantifying structural variants in chromosomes using landmark-based disparity

Abstract Chromosomal architecture has played a key role in the evolution of biodiversity. Detecting structural variants (SVs) on chromosomes has informed the study of speciation, sex determination, adaptation, and some of the earliest divergences in the tree of life. Here we present a computationally non-intensive approach, based on geometric morphometrics, that uses conserved DNA sequences as landmarks to quantify structural disparities of focal chromosomes across multiple species, individuals, or cell types. Based on two approaches, we show that this ‘geno-metric’ method can be applied at micro– and macroevolutionary scales to discover and diagnose SVs. Using human X-linked genes and ultraconserved elements as landmarks, we provide empirical demonstrations with amniote sex chromosomes, the Drosophila virilis group, and placental mammal genomes. Landmark-based structural disparity analysis effectively identifies chromosomal rearrangements and has parallels with traditional morphometrics regarding chromosome size, landmark orientation and landmark availability. Using simulations, we show that structural disparity inferred from ultraconserved elements is correlated with overall levels of chromosome evolution; an attribute which is consistent with observed disparity between and within mammalian orders. We found that the disparity patterns of SVs have significant phylogenetic signal, giving them broad importance for studying evolutionary biology. Structural disparity analyses are a valuable addition to the comparative genomic toolkit in that they offer an intuitive, rapid mechanism for detecting SVs associated with single copy genetic landmarks and the potential to reveal broader patterns of chromosome evolution related to expansions, contractions, rearrangements and phylogeny.