Preprint: FBXL3 missense variant links circadian clock to out-of-season breeding in sheep
A selective sweep analysis has identified a T183M substitution in the circadian regulator FBXL3 that is enriched in sheep breeds capable of breeding outside their natural season.
A preprint posted to bioRxiv reports that a missense mutation — T183M — in *FBXL3*, a core component of the SCF E3 ubiquitin ligase complex that sets mammalian circadian period, is associated with the ability of certain sheep breeds to exhibit oestrus outside the usual breeding season. The finding emerged from a selective sweep analysis comparing breeds with and without out-of-season reproductive activity.
*FBXL3* encodes an F-box protein that targets the circadian clock protein CRY for degradation, thereby controlling the period length of the molecular clock. The T183M allele showed markedly different frequency between seasonal and non-seasonal breeds, suggesting that variation in circadian period length may underpin differences in annual reproductive timing — a trait of considerable importance to the sheep industry, where year-round breeding can improve production efficiency.
The study connects circadian genetics with the circannual timing mechanisms that regulate photoperiod-responsive reproduction in mammals. This work is a preprint and has not yet been peer-reviewed; findings should be treated as preliminary.
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Primary sourcePreprint bioRxiv (Cold Spring Harbor Laboratory) · 2026-06-19A missense mutation in FBXL3 links circadian regulation to out-of-season estrus in sheep