As the study of isochores was de facto abandoned by most scientists, an alternative theory was proposed to describe the compositional organization of genomes in accordance with the most recent genomic studies. The Compositional Domain Model depicts genomes as a medley of short and long homogeneous and nonhomogeneous domains. The theory defines "compositional domains" as genomic regions with distinct GC-contents as determined by a computational segmentation algorithm. The homogeneity of compositional domains is compared to that of the chromosome on which they reside using the F-test, which separated them into compositionally homogeneous domains and compositionally nonhomogeneous domains based on the outcome of test. Compositionally homogeneous domains that are sufficiently long (≥ 300 kb) are termed isochores or isochoric domains. These terms are in accordance with the literature as they provide clear distinction between isochoric- and nonisochoric-domains.
A comprehensive study of the human genome unraveled a genomic organization where two-thirds of the genome is a mixture of many short compositionally homogeneous domains and relatively few long ones. The remaining portion of the genome is composed of nonhomogeneous domains. In terms of coverage, only 1% of the total number of compositionally homogeneous domains could be considered "isochores" which covered less than 20% of the genome.
Since its inception the theory received wide attention and was extensively used to explain findings emerging from over dozen new genome sequencing studies.
 However, many important questions remain open, such as which evolutionary forces shaped the structure of compositional domains and the ways they differ between different species.