Clonal dynamics deviate from neutral drift in zebrafish spermatogenesis

Abstract

Spermatogonial stem cells (SSCs) maintain male fertility, but how their clonal dynamics change with age remains poorly understood. Here, we use in vivo CRISPR barcoding in zebrafish to label SSCs and track their contributions to sperm production through monthly sampling across the fertile lifespan. We find that only a subset of embryonic germ cells contributes to adult sperm production and that the relative contributions of individual clones shift dramatically over time. To interpret these dynamics, we developed a mathematical model that quantifies clonal drift rates and formally tests neutral versus non-neutral hypotheses. Most SSC clones show significant evidence of drift, yet their dynamics are inconsistent with a neutral model where clones have equal fitness and their dynamics are driven solely by random chance. Instead, we observe heterogeneous clonal dynamics, including a positive relationship between clone size and drift rate. Together, these findings demonstrate that SSC clonal dynamics are non-neutral across the zebrafish reproductive lifespan with important implications for allele transmission.