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Kingdom Fungi: fungal phylogeny

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Kingdom Fungi: fungal phylogeny
and systematics

THOMAS G. MITCHELL

Origin of the Fungi 1 Phylum Chytridiomycota 9

Concepts and terms 2 Phylum Zygomycota 11
Phenotypes and molecular markers to Phylum Ascomycota 11
identify fungi 4 Phylum Basidiomycota 21
Phylogenetic methods 5 Clinical applications 21
Genomics 7 Acknowledgments 24
Classification 7 References 24

Taxonomy is often regarded as the dullest of animals) as well as in extrachromosomal forms. The
subjects, fit only for mindless ordering and cytoskeleton includes major proteins that evolved early
sometimes denigrated within science as mere and have been conserved throughout the evolution of
‘stamp collecting.’ If systems of classification eukaryotes, such as tubulin (which forms microtubules)
were neutral hat racks for hanging the facts of and actin (microfilaments).
the world, this disdain might be justified. But Two major lineages arose early, one led to the algae
classifications both reflect and direct our and terrestrial plants, and the other gave rise to
thinking. The way we order represents the ways fungi and animals (Figure 1). The common origins of
we think. Historical changes in classification are animals and fungi are supported by phylogenetic
the fossilized indicators of conceptual revolu- analyses of the nucleotide sequences of several
tions. (Gould 1996) conserved genes, such as the small subunit (SSU) 18S
and large subunit (LSU) 26S of ribosomal DNA
ORIGIN OF THE FUNGI (rDNA), elongation factor, tubulin, and actin (Bruns
et al. 1991; Baldauf and Palmer 1993; Wainright et al.
The evolutionary origins of biology began with the 1993), although not by sequences of the RNA poly-
prokaryotes, the Archaea, and Eubacteria. The Eukar- merase II gene (Sidow and Thomas 1994). Based on
yota, or eukaryotes, are believed to have evolved from phylogenetic studies, molecular clock estimations of the
prokaryotes about 1.6–2.1 billion years ago with the rate of mutation, and limited fossil data, the time when
emergence of protists (Javaux et al. 2001). The protists animals and fungi diverged has been estimated at
include protozoa, certain algae, and fungal-like organ- approximately 1.5 billion years ago (Heckman et al.
isms, the Oomycota. Eukaryotic cells are distinguished 2001; Hedges et al. 2004).
by a cytoskeleton and intracellular organelles, which are Most fungi grow vegetatively as yeasts or molds, and
usually enclosed by membranes. The endomembranes of fungal cells may have more than one nucleus. Similar to
eukaryotic cells include the nuclear membrane, endo- other eukaryotes, fungi typically contain mitochondria, a
plasmic reticulum, Golgi apparatus, peroxisomes, and Golgi apparatus, and endoplasmic reticulum. They also
the plasma membrane. Most of the DNA is organized contain vacuoles, but lack chloroplasts and pseudopodia.
into chromosomes and contained with the nucleus, but Most have cell walls composed of chitin and b-glucans,
DNA is also found in the mitochondria (in fungi and as well as other polysaccharides, proteins, and lipids.
2 Kingdom Fungi: fungal phylogeny and systematics

Chytridiomycota

Zygomycota
Fungi Urediniomycetes

Basidiomycota Ustilaginomycetes

Eukaryota Hymenomycetes
Animals

Archiascomycetes
Plants Ascomycota
Hemiascomycetes
Protoctista

Euascomycetes
Figure 1 Major kingdoms of the Eukaryota, the four phyla of the Fungi, and the three classes of the Basidiomycota and the
Ascomycota.

Collectively, fungi exhibit a rich diversity, inhabit relationships among organisms. Systematicists study the
every ecological niche on the planet, and manifest a relationships of organisms and the processes by which
variety of lifestyles. Most fungi are chemotrophic and they evolved and are maintained. Classification is the
secrete catabolic enzymes that digest vicinal substrates, assignment of organisms to defined groups. Systematics
which are absorbed, as are minerals, salts, and other entails nomenclature and taxonomy, the science of
small molecules, by passive or active transport mechan- naming and classifying organisms. Because of their
isms. Fungi distinctively utilize a-aminoadipic acid in the historical association with plants, the fungi are named
biosynthesis of lysine. As saprobic fungi proliferate in according to the rules established by the International
aquatic and terrestrial locales, they degrade organic Code of Botanical Nomenclature. However, reflecting
substrates for their nutrition, and in the process recycle their affinity with animals, the higher fungal groups are
the organic detritus of plants and animals. Other fungi called Phyla, not Divisions. Major taxonomic groups of
are exploited by industry for the production of fungi are denoted by the following suffixes: Phylum, -
secondary metabolites or pharmacological compounds. mycota; Subphylum, -mycotina; Class, -mycetes;
Some serve science as model eukaryotes for the study of Subclass, -mycetidae; Order, -ales; Suborder, -ineae;
cellular, molecular, and genetic processes (e.g. Sacchar- Family, -aceae; and Subfamily, -oideae. The basic taxon
omyces cerevisiae, Neurospora crassa). Many provide is the species. However, the species name is often the
gustatory pleasure, either directly (edible mushrooms, antepenultimate rank of classification, just above the
truffles, morels) or indirectly (bread, cheese, alcoholic variety and individual (Kirk et al. 2001).
beverages). Certain groups of fungi are intriguingly Each species is identified by its genus and species
specialized, and have the ability to entrap nematodes, name, followed if necessary by a varietal or subspecies
form symbiotic relationships (lichens), nourish or protect designation. A full descriptor of a given species will
plants (mycorrhizae and endophytes, respectively), or include the binomial in Italic font followed in non-Italic
produce disease in plants or animals. More than 80 000 font by the surname(s) of the author(s) who first
species of fungi have been described, but the total described and named the species and the year of its
number of extant fungal species has been estimated to publication, for example, Cryptococcus neoformans
be about 1 500 000 (de Hoog et al. 2000; Kirk et al. (Sanfelice) Vuillemin (1901). If a species name is modi-
2001). Compared to the enormous kingdom of fungi, the fied, the names of subsequent authors may be added.
number of infectious, or mycotic, species is minuscule. Whenever possible, the original isolate from which the
Nevertheless, the medical fungi exert a profound, global species was described becomes its permanent reference
impact on human health. Their numbers continue to or the type strain for that species, and it is deposited in
increase, but no one knows how many human patho- an established culture collection (e.g. American Type
genic fungi exist. To date, approximately 400 clinically Culture Collection, Centraalbureau voor Schimmel-
relevant species have been described (de Hoog et al. cultures). If a species is inadvertently described more
2000; Kirk et al. 2001; Howard 2003). than once, its name reverts to the original description
(with sanctioned exceptions for names with longstanding
CONCEPTS AND TERMS familiarity).
There are several definitions of a fungal species
Systematics aims to describe and organize biological (Taylor et al. 2000; Burnett 2003). Members of a species
diversity, usually by determining the phylogenetic are quite similar, if not identical, in their morphology,
 Concepts and terms 3

mode of reproduction, physiology and temperature and any synanamorphs of a fungal species comprise its
range, biochemical structure, ecology, and genomic holomorph.
sequence. Species have been historically demarcated Furthermore, the reproductive structures of many
on the basis of morphological and other phenotypic fungal species are indistinguishable. Mating between
similarities. Biological species are defined by mating fungal isolates usually constitutes evidence of species
compatibility, the abilities to engage in sexual reproduc- identity. However, isolates with identical anamorphs
tion and successfully interbreed, thus sharing a common may not be recognized as different species if they are
gene pool with other members of the species (Burnett incapable of sexual reproduction. Consequently, an
2003). Other criteria have been used to define certain anamorphic ‘species’ may represent more than one tele-
species, including both ecological isolation in nature omorphic species, and vice versa. The dermatophytes
and the host specificity of pathogenic fungi. Species may offer good examples: the geophilic anamorph Tricho-
also be identified by phylogenetic analyses, using phyton terrestre may represent three different tele-
molecular markers as characters to determine evolu- omorphs, Arthroderma quadrifidum, Arthroderma insin-
tionary relationships. Phylogenetic criteria define a gulare, or Arthroderma lenticulare. Similarly, the
species as the smallest recognizable population of indivi- teleomorphic species Arthroderma uncinatum has two
duals or lineage united by shared derived characters anamorphs, Trichophyton ajelloi and Trichophyton
(synapomorphy) (Burnett 2003; Vilgalys 2004). Mole- phaseoliforme (Summerbell and Kane 1997).
cular studies have discovered situations where organisms The apparent predominance of anamorphy among
were morphologically indistinguishable, similar in mycotic fungi may be advantageous for pathogenicity.
numerous other phenotypes, and occupied the same Asexual fungal species tend to consist of one to several
habitat (sympatric), but they were not members of the distinct clones or lineages, and sexual reproduction is
same species. One such cryptic species is Candida limited or absent. Evolution occurs by various genomic
dubliniensis, which was long misidentified as Candida mechanisms, as noted above, and the gradual accumula-
albicans (Sullivan and Coleman 1998; Sullivan et al. tion of spontaneous mutations (Taylor et al. 1999b;
2004). Another example is the discovery that the Taylor et al. 2000; Xu and Mitchell 2002). The environ-
common cause of coccidioidomycosis, Coccidioides mental growth conditions will subsequently promote the
posadasii, was for decades subsumed by the phenotypi- positive selection, survival, and proliferation of clones
cally similar species, Coccidioides immitis (Fisher et al. with favorable mutations. By contrast, sexual reproduc-
2002). tion offers the opportunity to more rapidly exchange
An important route to speciation occurs when genetic information. However, in sexually reproducing
organisms become geographically and reproductively populations, favorable combinations of mutations that
isolated (allopatry). Over time, mutations accrue, selec- arise in some lineages may be lost through subsequent
tive pressure or genetic drift may impact the organisms, recombination. Many fungi exhibit a mixture of both
and they become sufficiently divergent that mating with clonal reproduction, which can be favored under
the ancestral population is no longer possible. Advances uniform growth conditions, and sexual recombination,
in fungal genomics are beginning to discover some of which can be advantageous in changing environments.
the genetic mechanisms that may drive speciation, Perhaps as commensal and pathogenic fungi become
including mitotic recombination (parasexuality), gene more entrenched on the mammalian host, their need for
duplications, and chromosomal rearrangements and genetic variation is minimized, and anamorphy becomes
translocations (Lynch 2002; Wong et al. 2002; Dujon an important survival mechanism. The dermatophytes
et al. 2004). exemplify support for this concept. Except for Tricho-
The sexually reproductive life cycle of a fungal phyton mentagrophytes and Microsporum canis, the
species is its teleomorph, which indicates that the anthropophilic and zoophilic species exist only as
species has the ability to undergo meiosis and produce anamorphs (e.g. Trichophyton rubrum, Trichophyton
meiospores. The anamorph refers to mitotic or asexual tonsurans, Trichophyton verrucosum, Trichophyton
reproduction. If a teleomorphic species produces equinum, Microsporum ferrugineum, Epidermophyton
multiple anamorphs, they may be called synanamorphs. floccosum), but most of the saprobic, geophilic species
Since many fungal species lack a known teleomorph, or have teleomorphic states (e.g. Microsporum cookei,
were described before their sexual reproductive mode Microsporum gypseum, Microsporum persicolor)
was recognized, their names were based on their (Howard et al. 2003). The evolution to anthropophilism
anamorphic or asexual reproductive morphology and can also be associated with the loss of asexual sporula-
ontogeny. This method of classification relies on tion. Routine cultures of most geophilic species regularly
morphology and other phenotypes, and it may or may manifest both macroconidia and microconidia, but many
not reflect evolutionary relationships. Many fungi have human pathogens tend to produce only, or predomi-
both a teleomorphic and one or more anamorphic nantly, microconidia (Trichophyton soudanense, T.
species names, reflecting their separate description at rubrum, T. tonsurans, Trichophyton yaoundei), macro-
different times and places. The teleomorph, anamorph, conidia (E. floccosum), or neither (Microsporum
4 Kingdom Fungi: fungal phylogeny and systematics

audouinii, M. ferrugineum, Trichophyton concentricum, PHENOTYPES AND MOLECULAR

Trichophyton schoenleinii, T. verrucosum, Trichophyton MARKERS TO IDENTIFY FUNGI
violaceum).
Phylogenetics is the taxonomical classification of As summarized in Table 1, traditional methods of clas-
organisms that reflects their evolutionary relationships. sifying fungi utilize phenotypic differences in vegetative
Using molecular or phenotypic characters, a phyloge- and reproductive morphology (e.g. colonial and micro-
netic tree depicts the ancestor–descendant relationships morphology), physiology (e.g. patterns of assimilation
among organisms. Morphology – macroscopic, micro- and fermentation, temperature, and pH range of
scopic and ultrastructural – provided the original basis growth), the presence of structural macromolecules (e.g.
for classifying fungi, as well as other organisms, and cell wall polysaccharides, isoprene units of coenzyme Q),
proposing phylogenetic relationships. Molecular and sexual mating. Since most medical fungi do not
methods include comparative analyses of the nucleotide evince a teleomorph, their identification and classifica-
sequences of RNA and DNA and the amino acid tion have rested on phenotypic characteristics. Definitive
sequences of proteins (Hillis et al. 1996a). The most phenotypic features are often difficult to discern or
comprehensive phylogenies have been constructed from highly variable. Thus, for many pathogens, the species
comparisons of the highly conserved nucleotide boundaries are loosely defined. For example, any ellip-
sequences of ribosomal RNA, especially alignable tical, fermentative, nonpigmented, asexual yeast produ-
regions of the small (18S) and large (26S) subunits (SSU cing multilateral buds and pseudohyphae is likely to be
and LSU) of rDNA. placed in the genus Candida, which is large, multi-
A cluster of taxa on a branch of a phylogenetic tree or farious, and polyphyletic (Meyer et al. 1998; Diezmann
clade is monophyletic if all organisms in that group are et al. 2004).
known to have developed from a common ancestor, and Molecular markers are definitive and more stable than
all descendants of that ancestor are included in the most phenotypic attributes, and they are helping to
group. A group is paraphyletic if all the members have a resolve these issues. There is continuing progress in the
common ancestor but the group does not include all the biotechnology of rapid, high-throughput methods to
descendants of the common ancestor. Taxonomic groups genotype strains and the development of innovative
that contain organisms but not their common ancestor statistical approaches and software to analyze the data.
are called polyphyletic. Phylogenetic classifications aim Some of the more common DNA-based methods are
to group species such that every group is descended listed in Table 2, discussed in Laboratory
from a single common ancestor, and the elimination of diagnosis, and detailed in recent reviews (Bruns et al.
groups that are found to be polyphyletic often stimulates 1991; Taylor et al. 1999a; Mitchell and Xu 2003; Taylor
major revisions of the classification. and Fisher 2003).

Table 1 General phenotypic approaches to identify and characterize fungi

Phenotype category Observations (examples)
Morphology Teleomorph: Sexual reproduction (zygospore, ascocarp, basidiocarp)
Anamorph: Mitospore ontogeny and morphology (sporangia, conidiogenesis)
Vegetative yeast or hyphal morphology (septate, dematiaceous, Diazonium Blue B)
Colony texture, pigment, size
Septal pore type
Dimorphism
Structural Cell wall polysaccharides (chitin, glucans, mannans)
macromolecules Coenzyme Q isoprene units
Isozymes
Antigens
Metabolism Assimilation of particular compounds as sole nitrogen or carbon sources
Fermentation of various carbon compounds
Metabolic pathways
Vitamin requirements (biotin, thiamin)
Production of enzymes (proteases, phospholipases, urease, catalase, etc.)
Secondary metabolites (mycotoxins)
Growth parameters Optimum and tolerable range of temperature, pH, concentration of salts, oxygen
requirements, etc.
Susceptibility to Inorganic compounds (chlorine salts)
inhibitors Fungicides, detergents, organic compounds (canavanine, benomyl, etc.)
Drugs (antifungal antibiotics, cycloheximide)
Killer yeasts
Pathogenicity Host range
Virulence factors (adhesins, secretory enzymes, etc.)
 Phylogenetic methods 5

Table 2 General DNA-based methods in medical mycology

Application
Strain identification,
molecular epidemiology,
Method population genetics Species identification Phylogenetics and systematics
Electrophoretic karyotype X
RFLP X X
Southern hybridization X X
RAPD, PCR fingerprint, AFLP X X
Microsatellites X X
Microarrays X X
SNP, MLST, DNA sequencing X X X

Abbreviations: AFLP, amplified fragment length polymorphism; MLST, multilocus sequence typing; RAPD, random amplified polymorphic DNA; RFLP,
restriction fragment length polymorphism; SNP, single nucleotide polymorphism, detected by high-throughput, automated system. Microarray technology
is currently only theoretical.
Other methods: mol% G+C; DNA–DNA hybridization.
References: Bruns et al. 1991; Mitchell and Xu 2003; Taylor and Fisher 2003.

A molecular marker is defined as any identifiable region not widely applicable for large phylogenetic investiga-
of the genome. Some markers are better at discriminating tions. They usually reflect nucleotide sequence differ-
individual strains, discrete species or higher taxonomic ences resulting in the substitution of one or more amino
groups. For certain studies, it is desirable to use markers acids, which alter the chromatographic mobility of the
in specific genes, and for others, markers in noncoding, protein to enable detection (Brandt et al. 1993; Murphy
usually anonymous portions of the genome are preferable et al. 1996; Mitchell and Xu 2003).
because they are assumed to be neutral or unaffected by In summary, these markers and the attendant analy-
selective pressure. Molecular markers for fingerprinting tical software have greatly innovated the methods to:
medical fungi include allozymes, electrophoretic karyo-
. resolve taxonomic uncertainties
types, DNA hybridization probes, PCR-based genotypes,
. investigate the transmission of strains in local
endonuclease restriction fragment length polymorphisms
outbreaks
(RFLP), and DNA sequencing (Table 2).
. accurately identify fungi in clinical specimens
The comparison of nucleotide sequences among
. recognize strains with clinically important phenotypes
species has revolutionized phylogenetic studies. The most
(e.g. virulence factors, resistance to antifungal drugs)
reliable DNA markers identify nucleotide sequence
. analyze the genetic structure of populations of a
polymorphisms, such as single nucleotide polymorphisms
pathogen
(SNP), insertions or deletions (indels), and length varia-
. trace the evolution of mycotic species
tions in tandem oligonucleotide repeats (microsatellites).
. validate the medical relevance of strains used in basic
Such markers can be detected by an array of molecular
research, comparative genomics, and the development
techniques, such as PCR amplicon length polymorph-
of new antifungal antibiotics and diagnostic tests.
isms, differences in the lengths of RFLP, single-
strand conformational polymorphisms (SSCP), or direct
DNA sequencing of homologous genomic regions of PHYLOGENETIC METHODS
the strains or species under comparison [multilocus
sequence typing (MLST)]. These methods and their The sequences of any two or more related taxa can be
applications to fungal phylogenetics have been described compared to detect phylogenetic relationships. The
in several reviews (Berbee and Taylor 1999; Taylor et al. underlying assumptions are that with the passage of
2000; Mitchell and Xu 2003; Taylor and Fisher 2003). time, there is an increase in the number of mutations,
Some methods are more suitable for population and divergence, and phylogenetic distance between organ-
phylogenetic studies of closely related taxa and strains of isms and their genomic sequences. The ‘molecular clock’
a species, such as isozymes (see below), amplified frag- hypothesis assumes that molecules evolve in direct
ment length polymorphisms (AFLP), randomly ampli- proportion to time; consequently, the differences
fied polymorphism DNA (RAPD), and hybridization of between homologous DNA sequences (or proteins) can
nucleotide probes to electrophoretic blots of digested be used to estimate the elapsed time since the two DNA
genomic DNA (Bakkeren et al. 2000; Soll 2000; Mitchell sequences (or their taxa) last shared a common ancestor
and Xu 2003). (Hillis et al. 1996b; Hedges and Kumar 2004). However,
Protein polymorphisms, such as isozymes, provide the observed rate at which nucleotides change is not
excellent markers for population genetics, but they are constant. Some sequences exhibit less variation over
6 Kingdom Fungi: fungal phylogeny and systematics

time than expected because their functionality is essen- genetic distance. UPGMA also assumes that all taxa are
tial and lethal mutations are lost. This problem is usually equally distant from the root (i.e. assumes a molecular
obviated by analyzing sequences of noncoding DNA. clock) and thus yields symmetrical trees. NJ is a similar
However, after sufficient time, some nucleotides may distance method but does not assume a molecular clock.
undergo further mutation(s) and revert to the ancestral NJ initially calculates the net divergence of each taxon
sequence. Most algorithms to construct phylogenetic from all the others, which is the sum of the individual
trees consider such variables and produce a consensus or differences from the taxon. Next, the program selects
single ‘best’ tree with branches of optimal length and the pair of taxa that are least diverged and calculates
likelihood. The common approaches of phylogenetic their distances from the node that connects them. This
analysis include Neighbor-Joining (NJ), parsimony, node is substituted for the pair, and the process
Maximum Likelihood (ML), and Bayesian methods (Xu continues, reducing the matrix with each step. One of
and Mitchell 2002; Baldauf 2003b; Felsenstein 2003; the accessible programs for constructing phylogenies is
Holder and Lewis 2003). PAUP* (Swofford 2002; Hall 2004). UPGMA and NJ
The usual phylogenetic methods use algorithms that programs are the least computationally demanding of
are based on genetic distances, optimality criteria, such as the common methods and run very quickly on most
parsimony or ML, or Bayesian probabilities (Swofford computers. However, their speed sacrifices accuracy, as
et al. 1996). The first step involves the alignment of neither method attempts to optimize a tree to determine
nucleotide (or protein) sequences of the taxa being the best estimate. By contrast, MP, ML, and Bayesian
compared. The most popular distance methods are NJ inferences perform iterative rounds of optimization to
and Unweighted Pair-Group Method with Arithmetic find the best tree.
Mean (UPGMA), which estimate phylogenies based on An excellent test of the statistical support for each
the nucleotide differences among the taxa. Maximum branch of the tree is bootstrapping, which can be
Parsimony (MP) or ML apply optimality criteria to infer appliedto all methods (Felsenstein 1985). There is
phylogenies that minimize the number of evolutionary some debate about the interpretation of bootstrap values
steps required to explain the data. The selection of one or in phylogenetic analyses. For parsimony analysis,
more methods is governed by the number and diversity of bootstrap values >70 percent are usually considered
the taxa, as well as the sequences that are compared. acceptable, but for the other methods, values >90
Other considerations are the types of assumptions asso- percent are considered significant support for a clade.
ciated with a particular data set (e.g. constant or varying Bayesian probabilities often achieve >95 percent support
rate) and the required computational power, as algo- for branches.
rithms such as ML are more demanding than others. Unlike distance methods, MP seeks a tree(s) that
The products of these methods are phylogenetic trees, requires the minimum number of nucleotide (or other
which estimate the evolutionary history of a group of characters) changes. Therefore, MP only needs to
sequences. A phylogenetic tree is often rooted with an analyze informative sites, namely, nucleotide changes
outgroup of some evolutionary distance from the taxa that occur in two or more sequences. The algorithm then
being analyzed, which anchors the study taxa and provides determines which one or more of the possible tree(s)
structure for the tree. Two kinds of diagrams are requires the fewest number of changes.
commonly generated with rooted trees – cladograms and The ML approach is usually applied to a particular
phylograms. A cladogram presents only the nodes and tree or evolutionary model and computes the probability
branches. In a phylogram, branch length is proportional to of generating that tree from the dataset. ML seeks to
the evolutionary distance, providing a schematic depiction infer the tree with highest probability from the observed
of the number of character state differences (e.g. nucleo- sequence alignment.
tide substitutions) between the taxa on that branch. There A Bayesian analysis (BA) undertakes a succession of
are several excellent reviews of phylogenetic methods and iterative phylogenetic analyses, each of which employs
theory (Hillis et al. 1996a; Swofford et al. 1996; Felsenstein the optimized parameters of the previous analysis, until
2003; Holder and Lewis 2003; Hall 2004). a best tree or set of trees is obtained. BA resembles ML,
Distance methods approximate a phylogenetic tree by but ML searches for the best tree that maximizes the
estimating the relative number of nucleotide differences probability of observing the data for that tree, and
between each pair of taxa in a multiple alignment. This BA seeks the tree(s) that maximizes the posterior prob-
method usually assumes that the rate of mutation for the ability of the tree for that data. BA, which is commonly
aligned sequences is neutral, independent, and constant, employed with the MrBayes program, using the Metro-
and that the occurrence of multiple changes of the same polis-coupled Markov Chain Monte Carlo sampling
nucleotide(s) can be estimated. However, corrections for method, is more robust and exhaustive and will deter-
unequal substitution rates and other variables are mine the best set of trees (Huelsenbeck and Ronquist
commonly introduced. UPGMA is the simplest clus- 2001). These programs do their work by analyzing the
tering algorithm, which starts with the two most similar alignments, sequentially and repetitively comparing tree
sequences, and then sequentially adds taxa of increasing configurations to identify the tree or trees with the
 Classification 7

highest probability (Huelsenbeck et al. 2001; Holder and genes, as well as test the validity of phylogenetic
Lewis 2003; Hall 2004). methods (Hardison 2003).
In addition to genomic sequences, other molecular
characters and phenotypes are helpful in analyzing CLASSIFICATION
phylogenies. Certain cell wall polysaccharides are asso-
ciated with specific fungi, and the chemical or immuno- It has been difficult to resolve the ancestry of fungi and
logical detection of signature motifs can be used to iden- other eukaryotes, and analyses of various taxa and genes
tify fungi within those groups. Similarly, the capacity to have generated inconsistent phylogenies. Several issues
produce secondary metabolites and metabolic bypro- contribute to the problem of parsing these ancient
ducts (e.g. arabinitol) under the appropriate conditions lineages:
have sufficient specificity in clinical settings to be useful
. there is a dearth of fossil data
in diagnostic and prognostic tests, and these properties
. extant ancestral species have saturated their available
may be significantly correlated with certain taxonomic
mutable nucleotides, even back-mutating to their
lineages. These structural and metabolic compounds
original sequences
include coenzyme Q, which is a mitochondrial electron
. the results vary depending upon the selected taxa,
carrier with a varying number of isoprene units. The
genes, methods, and outgroups (Baldauf 2003a).
length of the isoprene chain is often the same within a
monophyletic group (Yamada et al. 1977). As noted Eventually these problems will be surmounted by
below, pathogenicity is a polyphyletic trait, as it evolved, increasing the number of taxa, using multigene datasets,
and was lost, multiple times throughout the history of and refining the phylogenetic methods.
fungi. Many of the attributes required for virulence by Lacking a consensus about the classification of the
certain fungal species are absent in other pathogens, as deep branches of the eukaryotic domain, a neutral
well as present in nonpathogens. There are many exam- approach has been to place the diverse ancestral phyla
ples of such properties, including dimorphism, secretory within the Kingdom Protoctista, which contains early
enzymes that catabolize host substrates, and cell wall eukaryotes that do not qualify as plants, animals, or fungi
ligands that promote adhesion to host cell receptors. At (Figure 1). Some of the 18–20 protoctistan phyla were
least one phenotype seems to be universally required if previously thought to be fungi, such as the Acrasiomy-
not necessarily sufficient for systemic fungal infection, cota (cellular slime molds), Myxomycota (plasmodial
growth at 37 C. slime molds), and Oomycota (water molds). The Proto-
ctista also includes the protozoa and algae. Table 3 lists
GENOMICS the higher taxa containing pathogenic fungi, including for
comparison a few prominent taxa that do not contain
The new disciplines of genomics and bioinformatics mammalian pathogens. At least two human pathogens
offer panoptic approaches to integrate molecular and are included among these ‘pseudofungi,’ Rhinosporidium
phenotypic data to elucidate fungal classification and seeberi in the Mesomycetozoa (Herr et al. 1999; Mendoza
evolution. The number of complete genome sequences et al. 2002) and Pythium insidiosum in the Oomycota
of mycotic, phytopathogenic, and model fungi is (Cooke et al. 2000; Tyler 2001).
increasing (www.genome.gov/11008243). These data- The true fungi are contained within the Kingdom
bases permit the comparison of not only genes but entire Eumycota, which is comprised of four phyla, the Chytri-
genomes, and there are multiple ways to exploit these diomycota, Zygomycota, Ascomycota, and Basidiomycota
resources. Following completion of the genome (Figure 1). Multiple phylogenetic analyses of molecular,
sequence of S. cerevisiae, sequences of 13 related hemi- morphological and other phenotypic data support the
ascomycetous yeasts were compared to evaluate the view that the Kingdom Fungi is monophyletic and origi-
conservation of chromosome maps and the similarity nated with the Chytridiomycota (Sugiyama 1998). Fungi
and synteny among genes (Gaillardin et al. 2000; were classically defined by the limits of mating, and three
Malpertuy et al. 2000; Souciet et al. 2000). Data from phyla – Zygomycota, Ascomycota, and Basidiomycota –
this ongoing multilaboratory project are regularly are named according to the product of sexual reproduc-
updated at the Genolevures (‘yeast gene’) web site: tion. For asexual fungi, the morphology and ontogeny of
cbi.labri.fr/Genolevures/. A subsequent comparison of their mitosporic reproductive structures became the basis
the genomic sequences of Candida glabrata, Debaryo- for the artificial form-taxa within the Class Deuter-
myces hansenii, Kluyveromyces lactis, S. cerevisiae, and omycetes or Fungi Imperfecti. This alternative approach
Yarrowia lipolytica, which manifest different reproduc- groups anamorphs according to their morphology, such
tive modes, led to the discovery of many new genes and as yeasts (blastomycetes) and molds (hyphomycetes).
gene families and specific mechanisms whereby these However, these morphology-based schemata do not repre-
yeast lineages have evolved (Dujon et al. 2004). sent phylogenetic relationships and thus do not reflect reli-
Comparative genomics approaches are being used to able biological or evolutionary information. Using avail-
identify phyla and other taxon- or pathogen-specific able SSU rDNA sequences, the phylogram in Figure 2
8 Kingdom Fungi: fungal phylogeny and systematics

Table 3 Higher taxa of mycotic fungi and selected pseudofungi

Kingdom Phylum Class Order Mycotic family or species
Protoctista Acrasiomycota
Hyphocytriomycota
Labyrinthulomycota
Myxomycota Dictyosteliomycetes
Myxomycetes Physarales
Mesomycetozoa Mesomycetozoea Dermocystida Rhinosporidium seeberi
Ichthyophonida
Oomycota Peronosporomycetes Peronosporales
Pythiales Pythium insidiosum
Saprolegniales
Eumycota Chytridiomycota Basidiobolus ranarum
Zygomycota Trichomyetes
Zygomycetes Entomophthorales Ancylistaceae
Basidiobolaceae
Mortierellales Mortierellaceae
Mucorales Cunninghamellaceae
Mucoraceae
Saksenaeaceae
Syncephalastraceae
Thamnidiaceae
Ascomycota Archiascomycetes Neolectomycetes Neolecta
Pneumocystidales Pneumocystidaceae
Taphrinales Taphrinaceae
Schizosaccharomycetes Schizosaccharomycetales Schizosaccharomycetaeae
Hemiascomycetes Saccharomycetales Ascoideaceae
Candidaceae
Dipodascaceae
Endomycetaceae
Eremotheciaceae
Lipomycetaceae
Metschnikowiaceae
Saccharomycetaceae
Euascomycetes Chaetothyriales Herpotrichiellaceae
Clavicipitales Clavicipitaceae
Dothideales Botryosphaeriaceae
Didymosphaeriaceae
Dothioraceae
Lophiostomataceae
Mycosphaerellaceae
Piedraiaceae
Eurotiales Eremomycetaceae
Monascaceae
Pseudeurotiaceae
Thermoascaceae
Trichocomaceae
Hypocreales Hypocreaceae
Lectiales Leotiaceae
Microascales Microascaceae
Onygenales Arthrodermataceae
Gymnoascaceae
Onygenaceae
Ophiostomatales Ophiostomataceae
Pezizales Ascodesmiaceae
Phyllachorales Phyllachoraceae
Pleosporales Leptosphaeriaceae
Pleosporaceae
Polystigmatales Polystigmataceae
Sordariales Chaetomiaceae
Coniochaetaceae
Lasiosphaeriaceae
Magnaporthaceae
Myxotrichiaceae
Sordariaceae

(Continued over)
 Phylum Chytridiomycota 9

Table 3 Higher taxa of mycotic fungi and selected pseudofungi (Continued )

Kingdom Phylum Class Order Mycotic family or species
Basidiomycota Hymenomycetes Agaricales Coprinaceae
Stereales Bjerkanderaceae
Corticiaceae
Schizophyllaceae
Tremellales Filobasidiaceae
Urediniomycetes Sporidiales Sporidiobolaceae
Ustilaginomycetes Malasseziales
Microstromatales
Tilletiales
Trichosporonales
Ustilaginales

References: de Hoog et al. 2000; Mendoza et al. 2002.

illustrates the relationships among many of the medical fungi (and countless saprobic anamorphs). Such species
fungi. are usually classified with phenotypically similar fungi
As noted above, traditional classifications of the fungi (Seifert and Gams 2001).
relied on morphological characters and sexual reproduc- The classification of fungi will continue to be a work
tion (Guarro et al. 1999; de Hoog et al. 2000). These in progress for many years. New species are constantly
approaches continue to serve well, especially for the being discovered. The phenotypic and genotypic char-
identification of taxa. Of course, clinical mycology has acterization of each new species allows it to be placed
more pragmatic goals: to obtain a rapid and accurate on the mycological tree, which will often lead to refine-
identification of a fungal isolate from a clinical ment and adjustment of various branches of the phylo-
specimen. Most human pathogenic fungi are geny. This ongoing process will further elucidate the
anamorphic, and with rare exceptions (the homothallic relationships among fungi and their evolution. Species,
ascomycete, Piedraia hortai), they are asexual when families, and orders will continue to be created,
causing an infection. Therefore, traditional and commer- conflated, and reorganized. Thus revision is constant and
cial methods have combined morphological and physio- inexorable, understandably but unfortunately causing
logical phenotypic characters to develop keys for the some confusion, as familiar fungal names and taxonomic
timely identification of fungal isolates from clinical associations are periodically supplanted. This perpetual
specimens. Expedient shortcuts utilizing physiological change is often accompanied by controversy and
tests are especially useful for the rapid identification of reasoned disagreement based on conflicting data or
yeasts (Freydiere et al. 2001). differing interpretations of the data.
Beyond the bedside, clinical mycology benefits from The protocols for naming new species and higher taxa
an authentic phylogeny of pathogenic fungi. Knowledge are well established, and mycologists follow the rules of
of the lineages and nearest relatives of the mycotic fungi Botanical Nomenclature. However, there is not a recog-
is useful because closely related species share similar nized mycological governing body to arbitrate contro-
genes, macromolecules, and biochemical processes. This versies and decide controversial issues. Lacking an offi-
information is invaluable in selecting comparative taxa cial consensus, the classification presented here is an
to investigate the specificity of new diagnostic tests and amalgam of several respected sources, including recent
antifungal antibiotics, as well as directing rational publications (de Hoog et al. 2000; Kirk et al. 2001;
studies of pathogenesis, virulence factors, and mechan- Howard 2003) and useful web sites, such as Myconet
isms of drug resistance. (www.umu.se/myconet/Myconet.html), the Fungal Tree
Modern systematics uses molecular data to assign of Life (ocid.nacse.org/research/aftol/), the Index
asexual species to their likely positions within the taxo- Fungorum (www.indexfungorum.org/Names/Names.asp),
nomic framework based on their most closely related Deep Hypha (ocid.nacse.org/research/deephyphae/index.
taxa, as determined by molecular and phenotypic simila- php?id=projects), and the Tree of Life Web Project
rities. The ultimate goal – to create a unified taxonomy (tolweb.org/tree?group=Fungi&contgroup=Eukaryotes).
that reflects the phylogenetic evolution of the fungi –
has been facilitated by advances in biotechnology, PHYLUM CHYTRIDIOMYCOTA
sequencing, and computer programs to analyze the data.
As molecular evolution is the foundation of biology, the Members of this phylum are organized into a single class
aim is to assign asexual species to their proper phyloge- with five orders. The Chytridiomycetes are characterized
netic place in the classification, and it is feasible with by motile asexual zoospores, and more than 900 species
sufficient molecular data and analyses. However, mole- have been described (de Hoog et al. 2000; Kirk et al.
cular data are lacking for many pathogenic anamorphic 2001). The Orders Neocallimasticales and Blastocladiales
 Acremonium kiliense
Paecilomyces lilacinus
100 Fusarium oxysporum
100 92 100 Scopulariopsis brevicaulis
Trichoderma viridae
100 100 Madurella mycetomatis
99 100 Neurospora crassa
Sporothrix schenckii
Alternaria alternata
Aspergillus fumigatus
Aspergillus nidulans
72 Penicillium chrysogenum
100 Lacazia loboi
Paracoccidioides brasiliensis
84 Blastomyces dermatitidis
Histoplasma capsulatum
100 100 100Microsporum canis
Trichophyton mentagrophytes
97 92
Trichophyton rubrum
Coccidioides immitis
Cladophialophora bantiana
84 Fonsecaea pedrosoi
84 Phialophora verrucosa
100 Phaeoannelomyces elegans
100 Exophiala jeanselmei
71 100 Rhinocladiella aquaspersa
Exophiala werneckii
Ashbya gossypii
100 85 Candida kefyr
Ascomycota Saccharomyces cerevisiae
100 Candida glabrata
Candida krusei
Candida guilliermondii
97 100 Candida albicans
Candida parapsilosis
100 Candida tropicalis
Candida lusitaniae
Geotrichum candidum
Taphrina pruni
Schizosaccharomyces pombe
100 Chryptococcus neoformans var. gattii
100 Cryptococcus neoformans var. grubii
100 Cryptococcus neoformans var. neoformans
Basidiomycota 100 Trichosporon asahii
100 93 Trichosporon inkin
Cryptococcus laurentii
99 98 Cryptococcus albidus
Malassezia furfur
100 Phanerochaete chrysosporium
100
94 Schizophyllum commune
76 100 Rhodotorula glutinis
78 Rhodotorula mucilaginosa
100 Sporidiobolus salmonicolor
Neolecta irregularis
Cokeromyces recurvatus
100 Rhizopus oryzae
Mucor indicus
Zygomycota 83 Mucor racemosus
76 100 Apophysomyces elegans
100 Saksenaea vasiformis
99 100 Absidia corymbifera
100 94 Rhizomucor pusillus
75 Cunninghamella bertholletiae
100 100 Syncephalastrum racemosum
81 100 Conidiobolus coronatus
100 Conidiobolus incongruous
Basidiobolus ranarum
100 Ichthyophonus hoferi (fish parasite)
93 Rhinosporidium seeberi
100 Pythium insidiosum
75 Salpingoeca infusionum (choanoflagellate)
100 Antipathes galapagensis (black coral)
91 Suberites ficus (sponge)

Figure 2 Phylogram of representative mycotic fungi. Single most likely tree based on a ML analysis of the nuclear SSU rDNA sequences. Nodes with statistically significant support by bootstrap
(>70 percent) or Bayesian (>95 percent) analysis are indicated by the values below or above the nodes, respectively.
 Phylum Ascomycota 11

contain intestinal anaerobes and invertebrate pathogens, The zygomycetous pathogens are listed in Table 4.
respectively. The Order Chytridiales has pathogens of Within the Entomophthorales, the two classically recog-
nematodes, rotifers, and amphibians. Phylogenetic nized pathogenic genera, Basidiobolus and Conidio-
evidence suggests that both the Chytridiomycota and the bolus, cause primary subcutaneous infections and are
Zygomycota are polyphyletic (Sugiyama 1998). responsible for subcutaneous phycomycosis and rhinoen-
Basidiobolus ranarum may be the sole human tomophthoromycosis, respectively (see
pathogen among the chytridiomycetes (Table 3). B. Subcutaneous zygomycoses). However, as noted above,
ranarum is now recognized as the only pathogenic species molecular phylogenies have indicated that B. ranarum
of Basidiobolus, as previously described mycotic species may be more closely related to nonflagellate chytridio-
(viz. Basidiobolus haptosporus and Basidiobolus meris- mycetes (Nagahama et al. 1995; Jensen et al. 1998;
tosporus) are considered synonymous (Ribes et al. 2000). James et al. 2000).
Based on several SSU rDNA phylogenies, B. ranarum Most of the pathogens in this phylum are members of
has been relocated from the Zygomycota to the Chytri- the Order Mucorales and agents of the more invasive
diomycota (Nagahama et al. 1995; Jensen et al. 1998; infection, mucormycosis, whose name refers to the order
James et al. 2000). As James et al. observed, Basidiobolus and not the genus, Mucor, which is a rare cause of
spp. are the only known nonzoosporic fungi that possess a disease. However, as elaborated in Systemic
nucleus-associated organelle (NAO) containing micro- zygomycosis, most clinical mycologists favor the term
tubules, although the number and arrangement of the ‘zygomycosis,’ referring to an infection caused by any
microtubules differ from those of the centriolar micro- member of the Class Zygomycetes. The most common
tubules of the chytrids (McKerracher and Heath 1985; agent of invasive zygomycosis in humans is Rhizopus
James et al. 2000). However, phylogenetic analyses of the arrhizus (Rhizopus oryzae) (Ribes et al. 2000).
a-tubulin and b-tubulin genes provided strong support for
classifying B. ranarum within the Zygomycetes (Keeling PHYLUM ASCOMYCOTA
2003). These discrepant results may be explained by the
apparently faster rate of evolution of the SSU rDNA of The Ascomycota is the largest fungal phylum, and it
the chytrids and zygomycetes compared with the tubulin embraces 90 percent of the nearly 400 pathogenic fungi
genes (James et al. 2000; Keeling 2003). Another phylo- (Table 5). Their evolution has been estimated to date
geny of these basal fungi analyzed sequences of the from 900 to 500 million years ago (Berbee and Taylor
largest subunit of the gene encoding the DNA-dependent 1993; Taylor et al. 1999; Hedges et al. 2004). Approxi-
RNA polymerase II (RPB1), and these results indicated mately 33 000 ascomycetous species have been
that B. ranarum is distantly related to the zygomycetes described, and they are unified by sexual reproduction
(Tanabe et al. 2004). that culminates in the production of asci and ascospores
(de Hoog et al. 2000; Kirk et al. 2001). In addition, most
PHYLUM ZYGOMYCOTA of the 16 000 anamorphic species of fungi, which were
first identified according to their conidial mitospores,
The Phylum Zygomycota has two classes, the Zygomy- have been placed within the existing ascomycetous clas-
cetes and the Trichomycetes, and together they contain sification based on their molecular and phenotypic affi-
about 1 100 described species (de Hoog et al. 2000; nities. The availability of nucleotide sequences has
Kirket al. 2001). The Trichomycetes are obligate para- enabled asexual fungi to be placed with confidence
sites of arthropods, but two orders of the Class Zygo- among their closest relatives. The Ascomycota is also
mycetes, Entomophthorales and Mucorales, have home to most of the lichenized fungi.
important mammalian pathogens. The vegetative During vegetative growth, ascomycetous fungi produce
hyphae of zygomycetous molds are coenocytic or spar- either budding or fission yeast cells or branching
sely septated. The zygomycetes are defined by the substrate (vegetative) and aerial (asexually reproductive)
mode of sexual reproduction, which is initiated by hyphae. Hyphal septa possess simple pores that permit
hyphal anastomosis between compatible mating types of cytoplasmic continuity between cells. Some species,
the same species. Mating compatibility is determined by including many important human pathogens, are
opposite alleles at the mating type locus. Following dimorphic, and the morphogenetic conversion to
fusion of the haploid nuclei, meiosis, and one mitotic hyphae or yeasts (or spherules) is triggered by environ-
division, one haploid nucleus usually survives to mental signals such as temperature, available nutrients,
develop into a zygospore. When exposed to the appro- or carbon dioxide concentration. The Phylum Ascomy-
priate growth conditions, the zygospore of Mucorales cota has three classes, the Archiascomycetes, the Hemi-
species will produce a sporangiophore and a spor- ascomycetes (yeasts), and the large Euascomycetes
angium, yielding asexual sporangiospores that germi- (molds). According to SSU rDNA sequence analyses,
nate to form vegetative haploid hyphae. Most members the Archiascomycetes contains taxa that arose before
of the Order Entomophthorales reproduce asexually the latter two classes, which are monophyletic lineages
with forcibly discharged conidia. (Bruns et al. 1992; Berbee and Taylor 1993; Nishida and
12 Kingdom Fungi: fungal phylogeny and systematics

Sugiyama 1994). Members of the Archiascomycetes are . asci that are formed singly or in chains (Kurtzman
highly diverse, encompassing mycelial species, fission and Fell 1998).
yeasts, and unicellular forms. The genera include many
Phylogenetic analyses of SSU rDNA and RNA poly-
nonpathogens, such as Protomyces and Saitoella, as well
merase II (RPB2) gene sequences support a single
as Taphrina, Schizosaccharomyces, and Pneumocystis
evolutionary origin of the Saccharomycetales (Berbee
(Table 5). Evidence from molecular and biochemical
and Taylor 1992; Liu et al. 1999). Perhaps the largest
studies indicates that some of these taxa are mono-
phylogenetic analysis of the Saccharomycetes entailed
phyletic, but the status of others is questionable (Sjam-
more than 500 species and a comparison of LSU rDNA
suridzal et al. 1997). Figure 3 depicts an rDNA phylo-
sequences (Kurtzman and Robnett 1998).
geny of representative ascomycetes.
The Saccharomycetales contains many yeasts of medical
importance, such as species of Candida, which are the most
Class Hemiascomycetes
prevalent pathogenic fungi (Table 5;
Management of superficial infections; 15, Superficial candi-
The Hemiascomycetes (yeasts) comprise one large
diasis; and 30, Candidiasis) (Calderone 2002). As
order, the Saccharomycetales, which was established in
mentioned earlier, Candida is a large and broadly
1960 by V.I. Kudrjavzev (Kurtzman and Fell 1998; Kirk
defined anamorphic genus with 163 species (Meyer et al.
et al. 2001). The monumental compendium of yeasts,
1998). They include C. albicans, C. glabrata, Candida
edited by Kurtzman and Fell, lists 42 teleomorphic and
parapsilosis, and Candida tropicalis. In a recent analysis
15 anamorphic genera of ascomycetous yeasts (including
of the medical yeasts and related hemiascomycetes, DNA
several genera of Archiascomycetes). The other indis-
sequences of six nuclear genes were analyzed using ML
pensable resource, written by Barnett et al. (2000),
and Bayesian phylogenetic methods to produce the phylo-
describes 678 species of ascomycetous and basidiomyce-
gram in Figure 4, which depicts the relationships of the
tous yeasts. Members of the Saccharomycetes are char-
most common mycotic yeasts with rare opportunists and
acterized by:
strict saprobes (Diezmann et al. 2004). During the transla-
. absent or only rudimentary hyphae tion of mRNA to polypeptides, several species of Candida
. vegetative cells that reproduce by budding or fission exhibit alternative codon usage; the codon CUG is
. cell walls that lack chitin translated as serine instead of leucine, as in most other

Table 4 Mycotic taxa of Zygomycota

Class Order Family Species
Zygomycetes Entomophthorales Ancylistaceae Conidiobolus coronatus
Conidiobolus incongruus
Conidiobolus lamprauges
Basidiobolaceae Basidiobolus
Mortierellales Mortierellaceae Mortierella polycephala
Mortierella wolfii
Mucorales Cunninghamellaceae Cunninghamella bertholletiae
Mucoraceae Absidia coerulea
Absidia corymbifera
Apophysomyces elegans
Chlamydoabsidia padenii
Mucor amphibiorum
Mucor circinelloides
Mucor hiemalis
Mucor indicus
Mucor racemosus
Mucor ramosissimus
Rhizomucor miehei
Rhizomucor pusillus
Rhizomucor variabilis
Rhizopus arrhizus (oryzae)
Rhizopus azygosporus
Rhizopus microsporus
Rhizopus schipperae
Rhizopus stolonifer
Saksenaeaceae Saksenaea vasiformis
Syncephalastraceae Syncephalastrum racemosum
Thamnidiaceae Cokeromyces recuvatus

References: Kurtzman and Fell 1998; Guarro et al. 1999; de Hoog et al. 2000.
 Phylum Ascomycota 13

Table 5 Mycotic taxa of the Phylum Ascomycota

Class Order Family Teleomorph Anamorph

Archiascomycetes Pneumocystidales Pneumocystidaceae Pneumocystis jiroveci

Schizosaccharomycetales Schizosaccharomycetaeae Schizosaccharomyces pombea
Taphrinales Taphrinaceae Taphrinaa
Hemiascomycetes Saccharomycetales Ascoideaceae Yarrowia lipolytica Candida lipolytica
Candidaceae Arxula
Blastobotrys
Candida albicans
Candida castelli
Candida glabrata
Candida haemulonii
Candida inconspicua
Candida intermedia
Candida maltosa
Candida norvegica
Candida parapsilosis
Candida rugosa
Candida tropicalis
Candida viswanathii
Candida zeylanoides
Dipodascaceae Geotrichum
Galactomyces geotrichum Geotrichum candidum
Dipodascus (Blastoschizomyces) Geotrichum capitatum
capitatus
Geotrichum clavatum
Endomycetaceae Stephanoascus ciferrii Candida ciferrii
Debaryomyces hansenii Candida famata
Pichia guilliermondii Candida guilliermondii
Pichia fermentans Candida lambica
Pichia norvegensis Candida norvegensis
Pichia (Hansenula) anomala Candida pelliculosa
Pichia jadinii Candida utilis
Eremotheciaceae Eremothecium gossypii Ashbya gossypiia
Lipomycetaceae Kluyveromyces marxianus Candida kefyr
Metschnikowiaceae Clavispora lusitaniae Candida lusitaniae
Clavispora opuntiaea
Metschnikowia pulcherrima Candida pulcherrima
Saccharomycetaceae Dekkera Brettanomyces
Debaryomyces
Zygoascus hellenicus Candida hellenica
Issatchenkia orientalis Candida krusei
Arxiozyma telluris Candida pintolopesii
Saccharomyces cerevisiae
Euascomycetes Chaetothyriales Herpotrichiellaceae Anthopsis deltoidea
Cladophialophora arxii
Cladophialophora bantiana
Cladophialophora boppii
Cladophialophora carrionii
Cladophialophora devriesii
Cladophialophora modesta
Exophiala bergeri
Exophiala castellanii
(Exophiala mansonii)
Wangiella dermatitidis
(Exophiala dermatitidis)
Exophiala jeanselmei
Exophiala lecanii-corni
Exophiala moniliae
Exophiala pisciphila
Exophiala salmonis
Exophiala spinifera
Fonsecaea compacta
Fonsecaea pedrosoi
Phaeoannellomyces
(Exophiala) elegans
Capronia semiimmersa Phialophora americana

(Continued over)
14 Kingdom Fungi: fungal phylogeny and systematics

Table 5 Mycotic taxa of the Phylum Ascomycota (Continued )

Class Order Family Teleomorph Anamorph
Phialophora bubakii
Phialophora europaea
Phialophora reptans
Phialophora repens
Phialophora richardsiae
Phialophora verrucosa
Ramichloridium obovoideum
(R. mackenziei)
Ramichloridium schulzeri
Rhinocladiella aquaspersa
Rhinocladiella atrovirens
Sarcinomyces phaeomuriformis
Veronaea botryosa
Xylohypha (Cladophialophora)
emmonsii
Clavicipitales Beauveria bassiana
Engyodontium album
Paecilomyces fumosoroseus
Paecilomyces javanicus
Dothideales Botryosphaeriaceae Botryosphaeria rhodina Lasiodiplodia theobromae
Botryosphaeria subglobosa Sphaeropsis subglobosa
Didymosphaeriaceae Neotestudina rosatii
Dothioraceae Discosphaerina fulvida Aureobasidium pullulans
Cyphellophora laciniata
Cyphellophora pluriseptata
Sydowia polyspora Hormonema dematioides
Hortaea (Phaeoannellomyces)
werneckii
Scytalidium dimidiatum
(Nattrassia mangiferae)
Scytalidium hyalinum
Pseudomicrodochium suttonii
Lophiostomataceae Madurella grisea
Madurella mycetomatis
Pseudochaetosphaeronema larense
Pyrenochaeta mackinnonii
Pyrenochaeta romeroi
Pyrenochaeta unguis-hominis
Tetraploa aristata
Mycosphaerellaceae Cladosporium cladosporioides
Cladosporium elatum
Mycosphaerella tassiana Cladosporium herbarum
Cladosporium oxysporum
Cladosporium sphaerospermum
Mytilinidiaceae Taeniolella exilis
Taeniolella stilbaspora
Piedraiaceae Piedraia hortai
Eurotiales Eremomycetaceae Eremomyces langeronii Arthrographis kalrae
Monascaceae Monascus ruber Basipetospora rubra
Pseudeurotiaceae Pseudeurotium ovale Sporothrix
Thermoascaceae Byssochlamys
Thermoascus crustaceus Paecilomyces crustaceus
Trichocomaceae Petromyces alliaceus Aspergillus alliaceus
Aspergillus avenaceus
Aspergillus caesiellus
Aspergillus candidus
Aspergillus carneus
Eurotium chevalieri Aspergillus chevalieri
Aspergillus clavato-nanicus
Aspergillus clavatus
Aspergillus conicus
Aspergillus deflectus
Neosartorya fischeri Aspergillus fischerianus
Fennellia flavipes Aspergillus flavipes
Aspergillus flavus

(Continued over)
 Phylum Ascomycota 15

Table 5 Mycotic taxa of the Phylum Ascomycota (Continued )

Class Order Family Teleomorph Anamorph
Aspergillus fumigatus
Aspergillus granulosus
Eurotium herbariorum Aspergillus glaucus
Aspergillus janus
Aspergillus japonicus
Emericella nidulans Aspergillus nidulans
Emericella echinulata Aspergillus nidulans
Aspergillus niger
Fennellia nivea Aspergillus niveus
Aspergillus ochraceus
Aspergillus oryzae
Eurotium repens Aspergillus reptans
Aspergillus restrictus
Aspergillus sclerotiorum
Aspergillus sydowii
Aspergillus tamarii
Aspergillus terreus
Emericella quadrilineata Aspergillus tetrazonus
Neosartorya pseudofischeri Aspergillus thermomutatus
Neosartorya spinosa Aspergillus spinosus
Emericella unguis Aspergillus unguis
Aspergillus ustus
Aspergillus varians
Aspergillus versicolor
Eurotium amstelodami Aspergillus vitis (Aspergillus hollandicus)
Paecilomyces lilacinus
Paecilomyces marquandii
Paecilomyces puntonii
Paecilomyces variotii
Paecilomyces viridis
Penicillium aurantiogriseum
Penicillium brevicompactum
Penicillium chrysogenum
Penicillium citrinum
Penicillium commune
Penicillium decumbens
Penicillium expansum
Penicillium griseofulvum
Penicillium marneffei
Penicillium piceum
Penicillium purpurogenum
Penicillium rugulosum
Penicillium spinulosum
Penicillium verruculosum
Polypaecilum insolutum
Hypocreales Hypocreaceae Neocosmospora vasinfecta Acremonium
Acremonium atrogriseum
Acremonium blochii
Acremonium curvulum
Acremonium falciforme
Acremonium hyalinulum
Acremonium kiliense
Acremonium potronii
Acremonium recifei
Acremonium roseogriseum
Acremonium strictum
Acremonium spinosum
Cylindrocarpon cyanescens
Nectria radicicola Cylindrocarpon destructans
Cylindrocarpon lichenicola
Fusarium antophilum
Cosmospora episphaerica Fusarium aquaeductuum
Fusarium chlamydosporum
Fusarium dimerum
Fusarium incarnatum

(Continued over)
16 Kingdom Fungi: fungal phylogeny and systematics

Table 5 Mycotic taxa of the Phylum Ascomycota (Continued )

Class Order Family Teleomorph Anamorph
Fusarium napiforme
Gibberella nygamai Fusarium nygamai
Fusarium oxysporum
Gibberella fujikuroi Fusarium proliferatum
Gibberella fujikuroi Fusarium subglutinans
var. subglutinans
Nectria haematococca Fusarium solani
var. breviconia
Gibberella moniliformis Fusarium verticillioides
Metarhizium anisopliae
Trichoderma harzianum
Hypocrea koningii Trichoderma konigii
Trichoderma longibrachiatum
Hypocrea pseudokoningii Trichoderma pseudokoningii
Hypocrea rufa Trichoderma viride
Leotiales Leotiaceae Ochroconis constricta
Ochroconis gallopavum
Ochroconis humicola
Ochroconis tshawytschae
Pleurophoma cava
Pleurophomopsis lignicola
Pleurophoma pleurospora
Microascales Microascaceae Petriella setifera Graphium
Pseudallescheria boydii Graphium eumorphum
Graphium putredinis
Petriella setifera Scedosporium
Pseudallescheria boydii Scedosporium apiospermum
Scedosporium prolificans (S. inflatum)
Microascus cinereus Scopulariopsis cinereus
Microascus cirrosus Scopulariopsis paisii
Microascus manginii Scopulariopsis candida
Scopulariopsis acremonium
Scopulariopsis asperula
Microascus brevicaulis Scopulariopsis brevicaulis (S. koningii)
Scopulariopsis brumptii
Scopulariopsis candida
Scopulariopsis flava
Scopulariopsis fusca
Onygenales Arthrodermataceae Epidermophyton floccosum
Keratinomyces ceretanicus
Arthroderma corniculatum Microsporum
Arthroderma borellii Microsporum amazonicuma
Microsporum audouinii
Arthroderma otae Microsporum canis
Arthroderma cajetani Microsporum cookei
Microsporum equinum
Microsporum ferrugineum
Arthroderma fulvum Microsporum fulvum
Arthroderma grubyi Microsporum gallinae
Arthroderma gypseum Microsporum gypseum
Arthroderma incurvatum Microsporum gypseum
Arthroderma obtusum Microsporum nanum
Arthroderma persicolor Microsporum persicolor
Microsporum praecox
Arthroderma racemosum Microsporum racemosum
Arthroderma grubyi Microsporum vanbreuseghemii
Arthroderma uncinatum Trichophyton ajelloi
Trichophyton concentricum
Trichophyton duboisii
Trichophyton equinum
Arthroderma gloriae Trichophyton gloriaea
Trichophyton gourvilii
Arthroderma vanbreuseghemii Trichophyton mentagrophytes

(Continued over)
 Phylum Ascomycota 17

Table 5 Mycotic taxa of the Phylum Ascomycota (Continued )

Class Order Family Teleomorph Anamorph
var. interdigitale
Trichophyton kanei
Trichophyton krajdenii
Trichophyton megninii
Arthroderma benhamiae Trichophyton mentagrophytes
Trichophyton phaseoliformea
Trichophyton raubitschekii
Trichophyton rubrum
Trichophyton schoenleinii
Arthroderma simii Trichophyton simii
Trichophyton soudanense
Arthroderma insingulare Trichophyton terrestrea
Arthroderma lenticulare Trichophyton terrestrea
Arthroderma quadrifidum Trichophyton terrestrea
Trichophyton thuringiense
Trichophyton tonsurans
Arthroderma gertleri Trichophyton vanbreuseghemii
Trichophyton verrucosum
Trichophyton violaceum
Trichophyton yaoundei
Gymnoascaceae Gymnoascella dankaliensis
Gymnoascella hyalinospora
Narasimhella hyalinospora
Malbranchea gypsea
Malbranchea pulchella
Arachnomyces nodosetosus Onychocola canadensis
Onygenaceae Ajellomyces dermatitidis Blastomyces dermatitidis
Aphanoascus fulvescens Chrysosporium
Arthroderma tuberculatum Chrysosporium
Nannizziopsis vriesii Chrysosporium
Chrysosporium inops
Aphanoascus keratinophilus Chrysosporium keratinophiluma
Chrysosporium pannicola
Uncinocarpus queenslandicus Chrysosporium queenslandicum
Chrysosporium tropicum
Uncinocarpus orissi Chrysosporium zonatum
Coccidioides immitis
Coccidioides posadasii
Ajellomyces crescens Emmonsia crescens
Emmonsia parva
Emmonsia pasteuriana
Ajellomyces capsulatus Histoplasma capsulatum
Ajellomyces capsulatus Histoplasma capsulatum
var. duboisii
Histoplasma capsulatum
var. farciminosum
Lacazia loboi
Uncinocarpus reesii Malbrancheaa
Neoarachnotheca keratinophila Myriodontium keratinophilum
Paracoccidioides brasiliensis
Ophiostomatales Ophiostomataceae Ophiostoma stenoceras Sporothrix
Sporothrix schenckii
Pezizales Ascodesmiaceae Cephaliophora irregularis
Phyllachorales Phyllachoraceae Plectosphaerella cucumerina Plectosporium tabacinum
Pleosporales Leptosphaeriaceae Leptosphaeria coniothyrium Coniothyrium fuckelii
Leptosphaeria senegalensis
Leptosphaeria thompkinsii
Microsphaeropsis olivacea
Pleosporaceae Alternaria alternata
Alternaria chartarum
Alternaria chlamydospora
Alternaria dianthicola
Lewia infectoria Alternaria infectoria
Alternaria longipes
Alternaria tenuissima

(Continued over)
18 Kingdom Fungi: fungal phylogeny and systematics

Table 5 Mycotic taxa of the Phylum Ascomycota (Continued )

Class Order Family Teleomorph Anamorph
Cochliobolus australiensis Bipolaris australiensis
Cochliobolus hawaiiensis Bipolaris hawaiiensis
Bipolaris papendorfii
Cochliobolus spiciferus Bipolaris spicifera
Botryomyces caespitosus
Corynespora cassiicola
Curvularia brachyspora
Curvularia clavata
Cochliobolus geniculatus Curvularia geniculata
Cochliobolus lunata Curvularia lunata
Cochliobolus pallescens Curvularia pallescens
Curvularia senegalensis
Cochliobolus verruculosus Curvularia verruculosa
Dichotomophthoropsis nymphaearum
Dissitimurus exedrus
Drechslera biseptata
Exserohilum longirostratum
Exserohilum mcginnisii
Setosphaeria rostrata Exserohilum rostratum
Mycocentrospora acerina
Papulaspora equi
Phaeosclera dematioides
Phaeotrichoconis crotalariae
Phoma dennissiii var. oculo-hominis
Phoma eupyrena
Phoma glomerata
Phoma herbarum
Phoma hibernica
Phoma minutella
Phoma minutispora
Phoma sorghina
Polycytella hominis
Ulocladium botrytis
Ulocladium chartarum
Polystigmatales Polystigmataceae Colletotrichum coccodes
Colletotrichum crassipes
Colletotrichum dematium
Glomerella cingulata Colletotrichum gloeosporioides
Glomerella tucumanensis Colletotrichum graminicola
Sordariales Chaetomiaceae Thielavia terrestris Acremonium alabamense
Ascotricha chartarum Dicyma ampullifera
Chaetomium atrobrunneum
Chaetomium funicola
Chaetomium globosum
Chaetomium murorum
Chaetomium perlucidum
Chaetomium (Achaetomium) strumarium
Corynascus heterothallicus Myceliophthora thermophila
Myceliophthora lutea
Phaeoisaria dematidis
Staphylotrichum coccosporum
Coniochaetaceae Acrophialophora fusispora
Coniochaeta ligniaria Lecythophora hoffmannii
Lecythophora mutabilis
Phaeoacremonium inflatipes
Phaeoacremonium parasiticum
Phaeoacremonium rubrigenum
Phialemonium curvatum
Phialemonium obovatum
Lasiosphaeriaceae Arnium leporinum
Arthrinium phaeospermum
Nigrospora sphaerica
Magnaporthaceae Omnidemptus sp. Mycoleptodiscus indicus
Myxotrichiaceae Myxotrichum deflexuma

(Continued over)
 Phylum Ascomycota 19

Table 5 Mycotic taxa of the Phylum Ascomycota (Continued )

Class Order Family Teleomorph Anamorph
Geomyces pannorum
Oidiodendron cerealis
Ovadendron sulphureo-ochraceum
Sordariaceae Neurospora sitophila Chrysonilia sitophila
Thermomyces lanuginosus
(Humicola lanuginosa)
Xylariaceae Nodulisporium

References: Summerbell & Kane 1997; Kurtzman & Fell, 1998; Guarro et al. 1999; de Hoog et al. 2000; Machouart-Dubach et al. 2002; Revankar et al.
2002; Barron et al. 2003; Schell 2003; Sigler 2003a, b; Summerbell 2003; Cano et al. 2004; Sutton et al. 2004.
a) Questionable human pathogen.

eukaryotes (Massey et al. 2003). However, Candida is not a Microsporum, Paracoccidioides, and Trichophyton. The
monophyletic genus, and species vary in codon usage as Arthrodermataceae, Onygenaceae, and Gymnoascaceae
well as the number of isoprene units in coenzyme Q and were subjected to a masterful phylogenetic investigation
other characters (Diezmann et al. 2004). that involved a comparison of sequences of both the SSU
Unlike molds, which are identified primarily by obser- and LSU rDNA using NJ and ML methods (Sugiyama et al.
ving their colonial and microscopic morphology, yeasts 2002). From this analysis of 80 taxa, four major clades
vary little in morphology and are routinely speciated emerged. One clade included saprobes and systemic patho-
according to a battery of physiological criteria (Frey- gens, while the Arthrodermataceae were ensconced in a
diere et al. 2001; Hazen and Howell 2003). However, a different clade. Two pathobiological phenotypes, keratino-
commercial method has been recently developed for the lysis and dimorphism, are likely apomorphic, deriving
automated sequencing of the D2 region of LSU rDNA independently by convergent evolution, as they occurred
to identify both yeast and mold cultures within 24 hours in taxa in different clades. For example, since C. immitis
(Hall et al. 2003, 2004). was in a different clade from the Ajellomyces spp., patho-
genicity and dimorphism are apparently apomorphic
Class Euascomycetes (Sugiyama et al. 2002).
Initially described in the 1840s, the dermatophytes are
This large class of molds holds most of the Ascomycota, among the earliest documented human pathogens
including most of the anamorphic taxa (see Table 5). (Howard et al. 2003). The many species of Microsporum
The phylogenies of numerous groups of Euascomycetes and Trichophyton are closely related and similar in their
have been analyzed using a number of gene sequences morphology, physiology, degradative enzymes (e.g. kera-
(e.g. SSU and LSU rDNA, RPB1, EF2) and phyloge- tinases, elastases), and antigens (Kane et al. 1997).
netic approaches (e.g. MP, NJ, Bayesian) (Prillinger et al. However, some species exhibit marked differences in
2002; Reeb et al. 2004). The number of orders and ecology and host range. As mentioned above, the evolu-
families remains in flux, and the classification of the tion of dermatophytes toward zoophilism and anthro-
Euascomycetes will likely be mutable for many years as pophilism correlates with the loss of both sexual and
there is a steady and natural accrual of new information asexual sporulation. Most of the clinical species are reso-
(Kirk et al. 2001; Prillinger et al. 2002; Eriksson et al. lutely anamorphic and defined by subtle phenotypic
2004). Some of the more medically relevant groups are features. After decades of taxonomic revisions, several
described below. molecular phylogenies are finally resolving the phylo-
geny of the dermatophytes, but classifying dermato-
ORDER ONYGENALES phytes remains a dynamic enterprise (Gräser et al. 1999;
Many notable pathogens are members of the Order Makimura et al. 1999).
Onygenales, which was originally defined using detailed
ORDER EUROTIALES
morphological observations and other phenotypic data
(Currah 1985). This order is noted for the production of In the Order Eurotiales, sexual reproduction results in
enclosed ascomata, either cleistothecia or gymnothecia. perithecia or cleistothecia, and the anamorphs produce
The anamorphs produce distinctive thallic conidia, such as a variety of morphologically distinct conidiophores and
macroconidia, microconidia, chlamydospores, and arthro- phialoconidia. As indicated in Table 5, the family
conidia. Two medically prominent families are the Arthro- Trichocomaceae includes Penicillium and Aspergillus
dermataceae, which contains the dermatophytes and (Berbee et al. 1995; LoBuglio and Taylor 1995;
related keratinophilic saprobes, and the Onygenaceae, Summerbell 2003). The Order Ophiostomatales
which includes the endemic, dimorphic pathogens contains the dimorphic Sporothrix schenckii and a
(Table 5). The more famous onygenalean genera are number of closely related phytopathogens (de Beer
Blastomyces, Coccidioides, Epidermophyton, Histoplasma, et al. 2003). Numerous dematiaceous pathogens are
20 Kingdom Fungi: fungal phylogeny and systematics

Acremonium kiliense
Paecilomyces lilacinus
100 Fusarium oxysporum
100 100 Lomentospora prolificans
97 100 Scopulariopsis brevicaulis
100 Trichoderma viride
100 79 Chaetomium globosum
100
Madurella mycetomatis
99 100 Neurospora crassa
Lecythophora hoffmannii
70 Sporothrix schenckii
100 Alternaria alternata
100 Curvularia brachyspora
Peziza quelepidotia
Aspergillus flavus
96 Aspergillus nidulans
Aspergillus versicolor
Aspergillus terreus
Aspergillus fumigatus
Aspergillus niger
99 Penicillium chrysogenum
79 Penicillium freii
Paecilomyces variotii
Blastomyces dermatitidis Euascomycetes
100
100 100 Histoplasma capsulatum subsp. duboisii
100 100 Histoplasma capsualtum subsp. farciminosum
Histoplasma capsulatum var. capsulatum
Lacazia loboi
98 Malbranchea gypsea
97 Paracoccidioides brasiliensis
Coccidioides immitis
Microsporum canis
100 100 Trichophyton georgiae
87 100 99 Trichophyton mentagrophytes
Trichophyton rubrum
Trichophyton tonsurans
100 Capronia pilosella
97 100 Cladophialophora carrionii
100 100 Phialophora verrucosa
70 100 Cladophialophora bantiana
100 Exophiala dermatitidis
97
97 Fonsecaea pedrosoi
99
Phaeoannellomyces elegans
70 Rhinocladiella aquaspersa
Cladosporium sphaerospermum
Dothidea insculpta
91 Exophiala werneckii
98 Scytalidium hyalinum
81 Ashbya gossypii
95 100 Candida kefyr
100 Candida sphaerica
95 87 Saccharomyces cerevisiae
70 Candida castellii
Candida glabrata
97 Candida krusei
100 100 Pichia fermentans
100 Pichia membranifaciens
70 Candida norvegica
100 Candida utilis
Candida guilliermondii
Debaryomyces carsonii Hemiascomycetes
Candida albicans
Candida dubliniensis
100 Candida maltosa
100 Candida parapsilosis
Lodderomyces elongisporus
97 Candida viswanathii
Candida norvegensis
100 Candida zeylanoides
100 Candida lusitaniae
100
100 Candida pulcherrima
Geotrichum candidum
Stephanoascus ciferrii
Yarrowia lipolytica
Neolecta irregularis
Schizosaccharomyces pombe Archiascomycetes
Taphrina pruni
Coprinus cinneraeus
Athelia bombacina Outgroup

0.005 substitutions/site

Figure 3 Phylogram of representative and related mycotic ascomycetes. Single most likely tree based on a ML analysis of the nuclear
SSU rDNA sequences. Nodes with statistically significant support by bootstrap (>70 percent) or Bayesian (>95 percent) analysis are
indicated by the values below or above the nodes, respectively. Vertical lines on the right denote the three classes of the Ascomycota.

classified in the Order Dothideales (Spatafora et al. taxa is the subject of ongoing investigations, many
1995; de Hoog et al. 1999; Sterflinger et al. 1999). familial relationships have been resolved; for example,
Although the exact phylogenetic placement of these the family Herpotrichiellaceae contains species of
 Clinical applications 21

Cladophialophora, Exophila, Fonsecaea, and Phialo- 1993, 1995b; McLaughlin et al. 1995; Prillinger et al.
phora (Haase et al. 1999). 2002).
In a superb review of the Eurotiales, which was Most described basidiomycetes are members of the
published in 2003 but apparently written in 2000, Class Hymenomycetes, and they share the feature of
Richard Summerbell questioned the validity of many distinctive, perforated, dolipore septa (Moore 1978). The
case reports attributable to species of Aspergillus largest subdivision of the Hymenomycetes is the Homo-
(Summerbell 2003). The following species are listed as basidiomycetes, which houses mushrooms, puffballs, and
pathogens in Table 5, but their status as agents of other higher fungi. The classification of the higher taxa
aspergillosis is questionable because of the lack of defi- of Hymenomycetes is not completely resolved (Binder
nitive documentation: Aspergillus glaucus group, Asper- and Hibbett 2002). Another significant clade of the
gillus reptans, Aspergillus restrictus, Aspergillus unguis, Hymenomycetes is the Tremellales, which contains
Aspergillus janus. Of course, many other species of many of the basidiomycetous yeasts (Swann and Taylor
Aspergillus have been recovered from patients but are 1995a, c; Fell et al. 2000). The genera of greatest clinical
not listed because they were isolated only as contami- importance are Filobasidiella (Cryptococcus) (Sivaku-
nants from nonsterile clinical specimens (e.g. skin, sputa, maran et al. 2003), Malassezia (Kano et al. 1999)
sinuses). Other Aspergillus spp. are listed even though Rhodosporidium (Rhodotorula), Sporidiobolus (Sporo-
they have to date only caused infection in nonhuman bolomyces), and Trichosporon (Gu eho et al. 1992; Sugita
mammals, such as Aspergillus rugulovalvus (Emericella et al. 2002).
rugulosa) in cattle and Aspergillus deflectus in dogs.
Nevertheless, they have been cited in numerous texts CLINICAL APPLICATIONS
and reviews. Exclusively nonmammalian pathogens are
not listed. As mentioned earlier, DNA sequences have been
exploited not only to determine phylogenetic relation-
PHYLUM BASIDIOMYCOTA ships but to develop molecular methods to identify
cultures and detect fungal DNA in clinical material, to
Each of the three classes of the Phylum Basidiomycota – genotype species and strains for molecular epide-
Urediniomycetes, Ustilaginomycetes, and Hymenomy- miology, and to analyze the population structure of
cetes – contains species of yeasts and molds, as well as pathogens (Taylor et al. 1999a; Burnett 2003; Xu and
species that are capable of infecting mammalian hosts. Mitchell 2003).
Similar to the Ascomycota, the basidiomycetes are Phylogenetic studies have greatly abetted efforts to
ubiquitous. Many are phytopathogens, such as the rusts develop more accurate methods to identify species (and
and smuts, which are found in the Orders Uredinales strains) of many pathogenic fungi. Signature DNA
and Ustilaginales, respectively. Approximately 30 000 sequences of the target species are identified, often
basidiomycetous species have been described, yet only within the rDNA gene cluster, and specificity can be
a dozen or so cause human infection (Table 6). (Toxi- evaluated by including the closest taxa based on phylo-
genic fungi, such as poisonous mushrooms, are not genies of the target species (Iwen et al. 2002). PCR
included in Table 6.) methods are rapid, definitive, specific, and considerably
The basidiomycetes are characterized by the sexual more accurate and reliable than conventional methods
production of basidia and basidiospores. Sexual repro- of identification. Increasing reports confirm the utility of
duction is initiated by the fusion of compatible mating PCR methods to identify isolates of dermatophytes
partners, and a dikaryon is often formed in which each (Kanbe et al. 2003; Shin et al. 2003), dimorphic patho-
cell contains two haploid nuclei, one from each partner. gens (Walsh et al. 2003), and opportunistic molds
This dikaryophase may be protracted, and the hyphae (Kanbe et al. 2002; de Aguirre et al. 2004) and yeasts
develop clamp connections to ensure that each cell (Elie et al. 1998; Ahmad et al. 2002; Luo and Mitchell
maintains the requisite two nuclei. The clamp connec- 2002; Selvarangan et al. 2003). A new commercial
tions are accompanied by complex septal pores. Clamp method, originally developed for the identification of
connections are only produced by basidiomycetes, but bacteria, has proven successful in identifying fungal
they are not made by every member of the Basidiomy- cultures (Hall et al. 2003, 2004). After amplifying the D2
cota. The signature feature of basidiomycetes is the region of the LSU rDNA of the isolate, the amplicon is
production of basidia, which culminates the sexual cycle. then purified, cycle-sequenced, and the nucleotide
The basidium is the site of karyogamy, which is followed sequence is compared with a database of D2 sequences
by meiosis and mitosis, typically yielding four haploid of >1 000 mycotic fungi to identify the closest taxon.
basidiospores. The basidiospores germinate to form Multiple isolates of the same species usually exhibit
vegetative septate hyphae or budding yeast cells. Similar <1.00 percent variation (Hall et al. 2003, 2004).
to the Ascomycota, much phenotypic and molecular The natural next step is to develop methods to recog-
evidence suggests that the Basidiomycota is nize and diagnose mycotic infections directly from
monophyletic (Oberwinkler 1987; Swann and Taylor clinical specimens, and many DNA probes and PCR
22 Kingdom Fungi: fungal phylogeny and systematics

38 Candida albicans CBS 1905

37 Candida albicans CBS 562

34 Candida dubliniensis
35 Candida maltosa

36 Candida tropicalis

Candida viswanathii Clade 1

29
33 Candida parapsilosis genotype I

31 Candida parapsilosis CBS 604

32
Candida parapsilosis genotype II
30
Candida parapsilosis genotype III

Lodderomyces elongisporus

Candida guilliermondii mmRL 1635

27
28 25 Candida guilliermondii mmRL 1636
26
Pichia guilliermondii

Candida guilliermondii mmRL 1759

19 Candida intermedia
24
23 Clavispora lusitaniae
20 22 Clade 2
Clavispora opuntiae
16
Metschnikowia pulcherrima

21 Candida zeylanoides
Pichia norvegensis
18
17 Debaryomyces carsonii
15
Debaryomyces etchellsii

Debaryomyces hansenii

14 Candida castellii
13 Candida glabrata

Saccharomyces cerevisiae
9
12 Eremothecium gossypii

10 Saccharomyces kluyveri
3 7
11 Kluyveromyces lactis
Clade 3
Kluyveromyces marxianus

8 Candida norvegica
4
Pichia jadinii
2
6 Issatchenkia orientalis
5 Pichia membranifaciens

1 Pichia fermentans

Yarrowia lipolytica

Stephanoascus ciferrii

Schizosaccharomyces pombe

Neurospora crassa

0.05 substitutions/site
 Clinical applications 23

Table 6 Mycotic taxa of the Phylum Basidiomycota

Class Order Family Teleomorph Anamorph
Hymenomycetes Agaricales Coprinaceae Coprinus cinereus Hormographiella aspergillata
Hormographiella verticillata
Stereales Bjerkanderaceae Bjerkandera adusta
Corticiaceae Phanerochaete Sporotrichum pruinosum
chrysosporium
Schizophyllaceae Schizophyllum commune
Tremellales Filobasidiaceae Cryptococcus albidus
Cryptococcus ater
Cryptococcus curvatus
Cryptococcus laurentii
Cryptococcus macerans
Filobasidiella bacillispora Cryptococcus neoformans
var. gattii
Filobasidiella neoformans Cryptococcus neoformans
var. grubii
Filobasidiella neoformans Cryptococcus neoformans
var. neoformans
Filobasidium Cryptococcus uniguttulatus
unigutttulatum
Trichosporonales Cryptococcus humicola complex
Trichosporon asahii
Trichosporon asteroides
Trichosporon cutaneum
Trichosporon inkin
Trichosporon loubieri
Trichosporon mucoides
Trichosporon ovoides
Urediniomycetes Sporidiales Sporidiobolaceae Rhodosporidium Rhodotorula glutinis
diobovatum
Rhodosporidium Rhodotorula glutinis
sphaerocarpum
Rhodosporidium Rhodotorula glutinis
toruloides
Rhodotorula minuta
Rhodotorula mucilaginosa
(R. rubra)
Sporidiobolus Sporobolomyces salmonicolor
salmonicolor
Sporidiobolus Sporobolomyces holsaticus
johnstonii
Sporobolomyces roseus

Ustilaginomycetes Malasseziales Malassezia furfur

Malassezia globosa
Malassezia obtusa
Malassezia pachydermatis
Malassezia restricta
Malassezia slooffiae
Malassezia sympodialis
Moniliella suaveolensa
Microstromatales Fugomyces (Cerinosterus)
cyanescens
Tilletiales Tilletiopsis minor

References: Kurtzman and Fell 1998; Guarro et al. 1999; de Hoog et al. 2000; Fell et al. 2000; Takashima et al. 2001.
a) Questionable human pathogen.

Figure 4 Combined ML analysis of six genes (ACT1, EF2, RPB1, RPB2, SSU and LSU rDNA) for 38 taxa of Hemiascomycetes and two
outgroup species, an Archiascomycetes (Schizosaccharomyces pombe) and a Euascomycetes (Neurospora crassa). The following nodes
are supported by heterogeneous Bayesian posterior probabilities >95 percent as calculated in the combined analysis: 2, 4, 5, 7–11, 13,
15, 16, 21–23, 25–38. Branch lengths leading to Yarrowia lipolytica (0.19157), and the outgroup taxa (0.31967) were shortened to fit
the figure. Vertical lines on right indicate the three major clades (Diezmann et al. 2004).
24 Kingdom Fungi: fungal phylogeny and systematics

tests have been developed to identify specific fungal Currah, R.S. 1985. Taxonomy of the Onygenales: Arthrodermataceae,
DNA in clinical specimens (Yeo and Wong 2002). These Gymnoascaceae, Myxotrichaceae and Onygenaceae. Mycotaxon, 24,
1–216.
topics are amplified in Laboratory diagnosis;
de Aguirre, L., Hurst, S.F., et al. 2004. Rapid differentiation of
and 5, Mycoserology and molecular diagnosis. Aspergillus species from other medically important opportunistic
molds and yeasts by PCR-enzyme immunoassay. J Clin Microbiol, 42,
3495–504.
ACKNOWLEDGMENTS de Beer, Z.W., Harrington, T.C., et al. 2003. Phylogeny of the
Ophiostoma stenoceras Sporothtix schenckii complex. Mycologia, 95,
This review was supported by grants from the NIH, AI 434–41.
25783, AI 28836 and AI 44975. Invaluable comments de Hoog, G.S., Zalar, P., et al. 1999. Relationships of dothideaceous
black yeasts and meristematic fungi based on 5.8S and ITS2 rDNA
were generously provided by Stephanie Diezmann and
sequence comparison. Stud Mycol, 43, 31–7.
Rytas J. Vilgalys. I am most grateful to Stephanie Diez- de Hoog, G.S., Guarro, J., et al. 2000. Atlas of clinical fungi, 2nd edition.
mann for generously creating the figures. Utrecht, The Netherlands: Centraalbureau voor Schimmelcultures.
Diezmann, S., Cox, C., et al. 2004. Phylogeny and evoluation of
Candida and related taxa: a multilocus analysis. J Clin Microbiol, 42,
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