Variation in the embryonic cell lineages of Caenorhabditis elegans natural populations

Abstract

Developmental variation has often been appreciated as a major phenotypic substrate of evolutionary innovation in multicellular organisms. Although quantification of developmental variation in isogenic populations has a long history, it has been difficult to accomplish across natural populations until recently. Given its invariant cell lineage, Caenorhabditis elegans represents an ideal model system for studying how natural diversity in development is expressed at the resolution of single cells, cell lineages, and the whole embryo. Using embGAN, a deep-learning pipeline that enables label-free lineage tracing without the bottleneck and potential confounding effects of generating transgenic strains, we reconstructed the early embryonic lineage of 78 embryos spanning eight genetic backgrounds, including six wild strains, and quantified cell-cycle timing with a lineage-aligned graph metric that separates global rescaling of developmental rate from localized changes in lineage structure. We found that cell-cycle timing differs reproducibly among genotypes, with between-strain variation consistently exceeding within-strain variation. The magnitude of this variation was itself genotype-specific and not correlated with levels of genetic divergence. Unlike the global shifts in the tempo of development that dominate divergence between species, these differences are predominantly in lineage patterning, changing the timing of specific divisions, and they align to cell fate. Thus, the invariant lineage of C. elegans is built on a structured, genotype-specific landscape of developmental variation, a potential source of trait variation from which drift in developmental systems can emerge.