Durham, NC, USA. Lowly places can provide clues to how the sexes evolved in higher animals, including humans. For instance, fungi don't have clear distinction between male and female varieties, but they do have sex differences. A team lead by Joseph Heitman, M.D. from Duke University Medical Center has isolated sex-determining genes from Phycomyces blakesleeanus, one of the oldest known types of fungi. The team's findings appear in the journal Nature, and have the potential for stimulating new research initiatives into sex development.

To identify the mating-type loci in Phycomyces, the researchers used a computer search to compare known mating-type loci in the genomes of other fungal lineages and then genetic mapping. "We employed a usual-suspects approach, comparing proteins between fungal types before identifying a candidate that appeared related in all lineages," says Heitman.

 

Within this stretch of DNA, they were able to isolate two versions of a gene that regulates mating, which they dubbed sexM, (sex minus) and sexP (sex plus). Strains of fungi with opposite versions of the sex genes are able to mate with each other.

 

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A pseudophore of the fungus Phycomyces blakesleeanus.

 

Pseudophores are aberrant sexual structures produced in strains of this zygomycete fungus that contain both copies of the sex genes.

 

Photo: Duke University Medical Center.

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Both versions of the gene, sexM and sexP, encode for a single protein called a high mobility group (HMG)-domain protein that leads to sex differentiation through an unknown process. This protein is very similar to one encoded by the human Y chromosome, called SRY, that when turned on leads a developing fetus to exhibit male characteristics. Heitman said this similarity suggests that HMG-domain proteins may mark the evolutionary beginnings of sex determination in both fungi and humans.

 

Heitman's team proposes that sexM and sexP were once the same gene that went through a mutation process called inversion. The new versions then evolved into two separate sex genes. The same process is most likely responsible for the evolution of the male Y chromosome, Heitman suggests.

 

Heitman hopes to next identify the sex region in another fungus, Rhizopus oryzae in order to better understand how HMG-domain proteins control sex determination in fungi. Rhizopus' genes can be cultured and chemically altered in a way that Phycomyces' sex genes can not.

 

"Rhizopus can be used to understand the influences of certain genes in lesser studied fungi much in the way we use mice to understand genetic effects in humans," explained Alexander Idnurm, Ph.D., the primary author on the study and recently appointed assistant professor at the University of Missouri-Kansas City (UMKC).

 

Another troubling mystery for Heitman is that certain younger fungal species lack HMG-domain proteins. He proposes that these proteins have been replaced with alternative transcription factors, which are proteins that turn genes on and off.

 

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Identification of the sex genes in an early diverged fungus p193. Alexander Idnurm, Felicia J. Walton, Anna Floyd & Joseph Heitman. Nature 451, 193-196. doi:10.1038/nature06453.

 

Abstract. Sex determination in fungi is controlled by a small, specialized region of the genome in contrast to the large sex-specific chromosomes of animals and some plants. Different gene combinations reside at these mating-type (MAT) loci and confer sexual identity; invariably they encode homeodomain, -box, or high mobility group (HMG)-domain transcription factors. So far, MAT loci have been characterized from a single monophyletic clade of fungi, the Dikarya (the ascomycetes and basidiomycetes), and the ancestral state and evolutionary history of these loci have remained a mystery. Mating in the basal members of the kingdom has been less well studied, and even their precise taxonomic inter-relationships are still obscure. Here we apply bioinformatic and genetic mapping to identify the sex-determining (sex) region in Phycomyces blakesleeanus (Zygomycota), which represents an early branch within the fungi. Each sex allele contains a single gene that encodes an HMG-domain protein, implicating the HMG-domain proteins as an earlier form of fungal MAT loci. Additionally, one allele also contains a copy of a unique, chromosome-specific repetitive element, suggesting a generalized mechanism for the earliest steps in the evolution of sex determination and sex chromosome structure in eukaryotes.

 

 

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