SummarySkin sun exposure induces two protection programs: stress responses and pigmentation, the former within minutes and the latter only hours afterward. Although serving the same physiological purpose, it is not known whether and how these programs are coordinated. Here, we report that UVB exposure every other day induces significantly more skin pigmentation than the higher frequency of daily exposure, without an associated increase in stress responses. Using mathematical modeling and empirical studies, we show that the melanocyte master regulator, MITF, serves to synchronize stress responses and pigmentation and, furthermore, functions as a UV-protection timer via damped oscillatory dynamics, thereby conferring a trade-off between the two programs. MITF oscillations are controlled by multiple negative regulatory loops, one at the transcriptional level involving HIF1α and another post-transcriptional loop involving microRNA-148a. These findings support trait linkage between the two skin protection programs, which, we speculate, arose during furless skin evolution to minimize skin damage.

In this study, we conduct an in-depth analysis of annexin proteins from a diverse range of invertebrate taxa, including the major groups that contain the parasites and vector organisms that are harmful to humans and domestic animals. Using structure-based amino acid sequence alignments and phylogenetic analyses, we present a classification for this protein group and assign names to sequences with ambiguous annotations in public databases. Our analyses reveal six distinct annexin clades, and the mapping of genes encoding annexins to the genome of the human blood fluke Schistosoma mansoni supports the hypothesis of gene duplication as a major evolutionary event in annexin genesis. This study illuminates annexin diversity from a novel perspective using contemporary phylogenetic hypotheses of eukaryote evolution, and will aid the consolidation of annexin protein identities in public databases and provide a foundation for future functional analysis and characterisation of these proteins in parasites of socioeconomic importance.