Conservative route to extreme genome compaction in a miniature annelid

Animal genomes vary in size by orders of magnitude. While genome size expansion relates to transposable element mobilisation and polyploidisation, the causes and consequences of genome reduction are unclear. This is because our understanding of genome compaction relies on animals with extreme lifestyles, such as parasites, and free-living animals with exceptionally high rates of evolution. Here, we decode the extremely compact genome of the annelid , a morphologically miniature meiobenthic segmented worm. With a ∼68 Mb size, genome is the second smallest ever decoded for a free-living animal. Yet, it retains many traits classically associated with larger and slower-evolving genomes, such as an ordered, intact Hox cluster, a generally conserved developmental toolkit, and traces of ancestral bilaterian linkage. Unlike animals with small genomes, the analysis of epigenome revealed canonical features of genome regulation, excluding the presence of operons and -splicing. Instead, the gene dense genome presents divergent kynurenine and Myc pathways, key physiological regulators of growth, proliferation and genome stability in animal cells that can cause small body size when impaired. Altogether, our results uncover a novel, conservative route to extreme genome compaction, suggesting a mechanistic relationship between genome size reduction and morphological miniaturisation in animals.