Significance Genomes of birds and reptiles, but not mammals, consist of a few large chromosomes and many tiny microchromosomes. Microchromosomes are gene-rich and highly conserved among birds and reptiles and share homology with one or more of the tiny chromosomes of an invertebrate that diverged from the vertebrate lineage 684 Ma. Microchromosomes interact strongly and crowd together at the center of cells, suggesting functional coherence. Many microchromosomes have been lost independently in turtles, snakes, and lizards as they have fused with each other or with larger chromosomes. In mammals they have completely disappeared, yet some chromosomes of the basal platypus line up with several microchromosomes, suggesting that they are the building blocks of the atypically variable chromosomes of mammals.