An N-Terminal Dimerization Domain Permits Homeodomain Proteins to Choose Compatible Partners and Initiate Sexual Development in the Mushroom Coprinus cinereus

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114

A key problem in evolutionary biology has been distinguishing the contributions of current and historical processes to the maintenance of genetic variation. Because alleles at self-recognition genes are under balancing selection, they exhibit extended residence times in populations and thus may provide unique insight into population demographic history. However, evidence for balancing selection and extended residence times has almost exclusively depended on identification of transspecific polymorphisms; polymorphisms retained in populations through speciation events. We present a broadly applicable approach for detecting balancing selection and apply it to the b1 mating type gene in the mushroom fungus Coprinus cinereus. The comparison of neutral molecular variation within and between allelic classes was used to directly estimate the strength of balancing selection. Different allelic classes are defined as encoding different mating compatibility types and are thus potentially subject to balancing selection. Variation within an allelic class, where all alleles have the same mating compatibility type, provided an internal standard of neutral evolution. Mating compatibility in this organism is determined by the complex A mating type locus, and b1 is one of several redundantly functioning genes. Consequently, we conducted numerical simulations of a model with two subloci and varying levels of recombination to show that balancing selection should operate at each sublocus. Empirical data show that strong balancing selection has indeed occurred at the b1 locus. The widespread geographic distribution of identical b1 alleles suggests that their association with differing A mating types is the result of recent recombination events.

Section: Resultsmentioning

confidence: 99%

The signature of balancing selection: Fungal mating compatibility gene evolution

May

Shaw

Badrane

et al. 1999

131

114

“…Cell fusion between compatible mates brings together two classes of homeodomain proteins that can heterodimerize in the cytoplasm via an N-terminal domain (3,28,38). NLSs on the HD1 protein permit the heterodimer to localize to the nucleus.…”

Section: Discussionmentioning

confidence: 99%

“…The two subunits are distinguished as homeodomain proteins HD1 and HD2 on the basis of conserved but distinctly different homeodomain motifs (2). After mating, HD1 and HD2 proteins heterodimerize to generate a dikaryon-specific transcriptional regulator that triggers the initial steps in sexual development (3). Heterodimerization plays a crucial role in mating partner recognition.…”

mentioning

confidence: 99%

“…The A mating type genes are multiallelic and there are an estimated 160 A mating specificities determined by three pairs of paralogous genes that encode functionally redundant proteins of both classes (the a, b, and d pairs) (4). The HD1 and HD2 proteins present in a cell before mating are unable to heterodimerize, whereas a compatible mating is one that brings together allelic versions of the proteins that can (3). Heterodimerization is mediated by the N-terminal domains of the proteins and serves the essential function of permitting only genetically different mating partners to generate the transcriptional regulator that promotes sexual development.…”

mentioning

confidence: 99%

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A role for heterodimerization in nuclear localization of a homeodomain protein

Spit

Hyland²,

Mellor³

et al. 1998

Self Cite

The A mating type genes of the mushroom Coprinus cinereus encode two families of dissimilar homeodomain proteins (HD1 and HD2). The proteins heterodimerize when mating cells fuse to generate a transcriptional regulator that promotes expression of genes required for early steps in sexual development. In previous work we showed that heterodimerization brings together different functional domains of the HD1 and HD2 proteins; a potential activation domain at the C terminus of the HD1 protein and an essential HD2 DNA-binding motif. Two predicted nuclear localization signals (NLS) are present in the HD1 protein but none are in the HD2 protein. We deleted each NLS separately from an HD1 protein and showed that one (NLS1) is essential for normal heterodimer function. Fusion of the NLS sequences to the C terminus of an HD2 protein compensated for their deletion from the HD1 protein partner and permitted the two modified proteins to form a functional transcriptional regulator. The nuclear targeting properties of the A protein NLS sequences were demonstrated by fusing the region that encodes them to the bacterial uidA (␤-glucuronidase) gene and showing that ␤-glucuronidase expression localized to the nuclei of onion epidermal cells. These observations lead to the proposal that heterodimerization regulates entry of the active transcription factor complex to the nucleus.

“…In the dikaryon the formation of one active heterodimer is sufficient for the initiation of sexual development. As in U. maydis, heterodimerization of two homeodomain proteins occurs via their Nterminal variable domains (33,34). In contrast to U. maydis, however, it has been shown for C. cinereus and S. commune that in the heterodimeric complex only one of the homeodomains is required for biological activity (35,36).…”

Section: Discussionmentioning

confidence: 99%

Single-chain fusions of two unrelated homeodomain proteins trigger pathogenicity inUstilago maydis

Romeis

Kämper

Kahmann

1997

Pathogenic and sexual development of the fungus Ustilago maydis, the causal agent of corn smut disease, is regulated by heterodimerization of two unrelated homeodomain proteins bE and bW, both encoded by the multi-allelic b mating-type locus. This complex can only be formed if the two proteins are derived from different alleles. The heterodimer is believed to function as a transcriptional regulator that binds to target sites upstream of developmentally regulated genes. We have synthesized a translational fusion in which bE is tethered to bW by a designed f lexible kink region. U. maydis strains expressing this synthetic b-fusion become pathogenic for corn illustrating that the single-chain fusion substitutes for the active bE͞bW heterodimer. Synthetic b-fusions in which bE and bW originate from the same allele as well as fusions deleted for the dimerization domains were shown to be active while both homeodomains were required for function. Such active fusion proteins are expected to be instrumental in the identification of pathogenicity genes.