Interestingly, the two sex genes are differentially regulated: the promoter of the sexP genes in four known Mucorales fungi includes a CCAAT box that is not found in the promoter of the sexM genes.[28]

Indeed, sexM is expressed exclusively during mating, whereas sexP is expressed during both vegetative growth and mating. These expression patterns of the two sex gene are concordant across P. blakesleeanus, M. mucedo, and M. circinelloides.[23, 28] Interestingly, the SexM protein contains a nuclear localisation signal sequence and is localised to nuclei[28]; the localisation of SexP has not yet been established. In M. mucedo and M. circinelloides, when the mating pheromone trisporic acid is supplemented during vegetative growth, sexM is expressed at a higher level, which coincides with its LBH589 mw expression pattern during INCB024360 nmr mating[28] (S. C. Lee and J. Heitman unpublished

data). This observation provides a connection between the sex locus and trisporic acid. However, the sex locus and the genes involved in trisporic acid synthesis are unlinked[28] and a direct connection between the sex locus and trisporic acid production is yet to be addressed. High mobility group gene(s) may be a sex determinant and function during mating in another basal fungal lineage, the Arbuscular Mycorrhizal Fungi (AMF). Rhizophagus irregularis is a plant-associated AMF and its genome encodes at least 76 HMG domain proteins, which were identified based on transcript expression analysis.[29] Subsequent analysis revealed that the genome of R. irregularis encodes 146 HMG gene copies.[30] The AMF have long been known as an asexual fungal lineage; however, the presence of multiple HMG genes in the AMF genome may suggest that bona fide sexual development occurs in this fungal lineage and that the HMGs serve as a sex determinant and play roles in mating. The ascomycete Podospora next anserina encodes 12 HMG protein genes, 11 of which are sex determinants or are involved in sexual reproduction,[31] suggesting that the HMG genes can be functionally specialised or have been

adapted during mating in this fungal lineage, which further supports that this presence of HMG genes can imply the presence of sexual development in the AMF lineage. Although the RNA helicase gene rnhA flanking the sex genes is highly conserved between the two mating types, there is some evidence that the sex locus can expand to include the rnhA gene (see below). This may indicate that the RnhA helicase functions during mating in the Mucorales, especially in meiotic silencing, which can involve a suppression of expression of unpaired DNAs during mating. In Neurospora crassa SAD-3 is a putative RNA helicase that is a homolog of RnhA. SAD-3 plays a role in meiotic silencing.[32] Schizosaccharomyces pombe Hrr1 is also an RNA helicase homolog and required for RNAi-induced heterochromatin formation.[33] Both SAD-1 and Hrr1 are known to interact with an RNA-directed RNA polymerase and Argonaute.