The cell morphological diversity of Saccharomycotina yeasts

Abstract

The ∼1 200 known species in subphylum Saccharomycotina are a highly diverse clade of unicellular fungi. During its lifecycle, a typical yeast exhibits multiple cell types with various morphologies; these morphologies vary across Saccharomycotina species. Here, we synthesize the evolutionary dimensions of variation in cellular morphology of yeasts across the subphylum, focusing on variation in cell shape, cell size, type of budding, and filament production. Examination of 332 representative species across the subphylum revealed that the most common budding cell shapes are ovoid, spherical, and ellipsoidal, and that their average length and width is 5.6 μm and 3.6 μm, respectively. 58.4% of yeast species examined can produce filamentous cells, and 87.3% of species reproduce asexually by multilateral budding, which does not require utilization of cell polarity for mitosis. Interestingly, ∼1.8% of species examined have not been observed to produce budding cells, but rather only produce filaments of septate hyphae and/or pseudohyphae. 76.9% of yeast species examined have sexual cycle descriptions, with most producing one to four ascospores that are most commonly hat-shaped (37.4%). Systematic description of yeast cellular morphological diversity and reconstruction of its evolution promises to enrich our understanding of the evolutionary cell biology of this major fungal lineage.

Full text

FEMS Yea st Resear c h , 2024, 24 , 1–9
DOI: 10.1093/femsyr/foad055
Ad v ance access publication date: 23 December 2023
Minire vie w
The cell morphological di v ersity of Saccharomycotina
yeasts
Christina M. Chavez
1 ,2
, Marizeth Gr oenew ald
3
, Amanda B. Hulfachor
4
, Gideon Kpurubu
1 ,2
, Rene Huerta
1 ,2
, Chris Tod d Hittinger
4
,
Antonis Rokas
1 ,2 ,*
1
Department of Biological Sciences, Va nde rbi lt University, Nashville, TN 37235, United States
2
Evolutionary Studies Initiative, Vanderb ilt University, Nashville, TN 37235, USA
3
Wes terdijk Fungal Biodiversity Institute, Utrecht 3584, the Netherlands
4
Labor atory of Genetics, DOE Gr eat Lakes Bioener gy Researc h Center, Wisconsin Ener gy Institute , Center for Genomic Science Inno v ation, J. F. Cr ow Institute for the
Study of Evolution, University of Wisconsin-Madison, WI 53726, United States
∗Corresponding author. Department of Biological Sciences and Evolutionary Studies Initiative, Vander bil t University, VU Station B#35-1634, Nashville, TN 37235,
USA. E-mail: antonis.r okas@v anderbilt.edu
Editor: [Daniela Delneri]
Abstract
The ∼1 200 known species in subphylum Sacchar om ycotina are a highly diverse clade of unicellular fungi. During its lifecycle, a typical
yeast exhibits multiple cell types with various morphologies; these morphologies v ar y acr oss Sacchar om ycotina species. Here , w e syn-
thesize the ev olutionar y dimensions of variation in cellular morphology of yeasts across the subphylum, focusing on variation in cell
shape , cell size , type of budding, and lament pr oduction. Examination of 332 r e pr esentati v e species acr oss the subphylum r ev ealed
that the most common budding cell shapes are ovoid, spherical, and ellipsoidal, and that their av era ge length and width is 5.6 μm
and 3.6 μm, r especti v el y. 58.4% of yeast species examined can produce lamentous cells, and 87.3% of species r e pr oduce asexuall y by
multilater al budding, whic h does not r equir e utilization of cell polarity for mitosis. Inter estingl y, ∼1.8% of species examined have not
been observed to produce budding cells, but rather only produce laments of septate hyphae and/or pseudohyphae. 76.9% of yeast
species examined have sexual cycle descriptions, with most producing one to four ascospores that are most commonly hat-shaped
(37.4%). Systematic description of yeast cellular morphological di v ersity and reconstruction of its evolution promises to enrich our
understanding of the ev olutionar y cell biology of this major fungal lineage.
Ke yw ords: ev olutionar y cell biology; cell size; cell shape; budding; h yphae; pseudoh yphae; cell type; Sacchar om ycotina
Introduction
Yeasts are unicellular fungi and hav e e volv ed m ultiple times in-
dependentl y acr oss the fungal kingdom (Na gy et al. 2014 , Li et al.
2021 ). Yea st s are free-living organisms that inhabit diverse ter-
restrial, aquatic, and marine environments on every continent,
forming associations with many plant, fungal, and insect species
(Kurtzman et al. 2011 ). The most species-rich lineage of yeasts is
that of the ∼1200 species in the subphylum Sacc harom ycotina (phy-
lum Ascom ycota ), whic h we will her eafter r efer to as yeasts. Yeast
species display a wide diversity of ecological lifestyles (Opulente
et al. 2018 ), partaking in m utualistic, competitiv e, opportunis-
tic , parasitic , or pathogenic relationships with other organisms
(Kurtzman et al. 2011 ). Se v er al yeast species ar e of importance to
diverse industries and human affairs, such as the baker’s yeast
Sacc harom yces cerevisiae (baking, br e wing, wine-making, biotec h-
nology); the human pathogens Candida albicans , Candida auris ,
and Nakaseomyces glabratus ( syn. Candida glabrata) ; and the plant
pathogens in the genus Eremothecium.
Yea st species in the Sacc harom ycotina can pr opa gate both
thr ough mainl y mitosis and often meiosis, gener ating differ ent
cell types (Herskowitz 1988 , Fischer et al. 2021 ). We refer to this
type of cellular mor phological v ariation as de v elopmental v aria-
tion. De v elopmental v ariation of cellular mor phology can be ob-
served in cell type differentiation that occurs during a yeast life
c ycle, as w ell as at various phases of cell cycle pr ogr ession in mito-
sis and meiosis of either haploid or diploid cells (Fig. 1 ). Yeasts un-
dergo cellular division and reproduction through mechanisms of
division, germination, and lamentous growth to result in various
cell types, such as budding cells, ascospores, and (pseudo)hyphae,
in which cells utilize polarization for successful growth (Bi and
Park 2012 ).
The de v elopmental v ariation exhibited b y y east species is often
dependent on en vironmental conditions , such as nutrient avail-
ability and temper atur e . For example , certain species primarily
grow as unicellular cells, but they can switch to a multicellu-
lar state through lamentous growth under the inuence of spe-
cic envir onmental str essors (Ruiz-Herr er a and Sentandr eu 2002 ,
Cullen and Spr a gue 2012 , Rupert and Rusc he 2022 ). Mitosis of ha p-
loid or diploid daughter cells enables yeasts to continue budding
and replicating so long as nutrients continue to be a vailable . Some
species of Sacc harom ycotina can under go mitosis to r esult in la-
mentous growth through the production of hyphae and pseudohy-
phae. Budding and pseudohyphae cells undergo polarized growth
during the G1 phase of the cell cycle, while hyphal growth does
Recei v ed 7 Mar c h 2023; revised 4 November 2023; accepted 22 December 2023
©The Author(s) 2023. Published by Oxford Uni v ersity Pr ess on behalf of FEMS. This is an Open Access article distributed under the terms of the Cr eati v e
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2 | FEMS Yea st Resear c h , 2024, Vol. 24
F igure 1. Generalized life c ycle of y east species in the subphylum Sacc har om ycotina. (1) Bud ding, including unipolar, bipolar, and m ultilater al budding
types. Note that the shapes and sizes of budding cells vary across species (see Fig. 2 ). (2) Haploid mitosis (dark blue = type a haploid, light blue = type
αha ploid). (3) Ha ploid mating of opposite types, possibl y after mating-type switc hing (Kr assowski et al. 2019 ). (4) Diploid mitosis (green = diploid a/ α).
(5) Diploid meiosis (purple = ascus with four ascospores). Note that the shapes and sizes of asci and ascospores vary across species (see Fig. 3 ). (6)
Filamentous growth as a result of an environmental change, such as a temperature increase and/or nutrient limitation (orange = pseudohyphae,
y ello w = true hy phae). Note that the known life cycles of se v er al species in the subphylum differ from this generalized version (e.g. several species are
not known to have a sexual stage).
not occur during the cell cycle, and instead depends on contin-
uous polarized growth without cell separation (Diepeveen et al.
2017 ).
In addition to de v elopmental v ariation, yeasts exhibit e volu-
tionary variation (Kurtzman et al. 2011 ). Evolutionary variation of
cellular morphology is characterized by the different morpholo-
gies of the same cell type across yeast species (Fig. 2 ). Population-
le v el v ariation in cellular morphology between individual cells
within a species has also been observed (Skelly et al. 2013 , Yvert
et al. 2013 , Jung et al. 2016 ). Although it is well known that dif-
ferent species and clades (e.g. taxonomic orders) exhibit distinct
morphologies and that the genomes of yeasts are fast-evolving
and highl y div erse (Shen et al. 2018 , 2020 , Gr oene wald et al. 2023 )
(e.g. at the le v el of pr otein sequence div er gence, S. cerevisiae is as
distantl y r elated to C. albicans as humans are to sponges), whether
this genomic variation is associated with cellular morphological
v ariation r emains poorl y understood.
Species in the Sacc harom ycotina exhibit extensiv e de v elopmen-
tal (Fig. 1 ) and evolutionary (Figs 2 –4 ) variation in their cell sizes
and shapes. Examination of cellular phenotypes across yeast
species and orders r e v eals div erse mor phologies that ar e atypical
of or absent from S. cerevisiae , the premier model organism not
just for yeasts, but for unicellular eukaryotes in general. This
e volutionary v ariation in cell sha pe and size may stem fr om
stochasticity in the form of genetic and envir onmental v ariance
(i.e. growth conditions) (Lynch et al. 2014 ). T hus , full understand-
ing of the evolutionary variation of cellular morphology requires
also examining genomic v ariation, v ariation in gene/protein
networks, and variation in environmental conditions involved in
its determination.
Although the Sacc harom ycotina subphylum harbors abundant
e volutionary v ariation of cell sha pes and sizes that allows for phy-
logenetic comparison across both closely related and highly diver-
gent taxa, this diversity of cell morphology has not been system-
aticall y c har acterized. This r e vie w aims to ll this ga p by synthe-
sizing the phenotypic diversity of cell morphology of evolutionary
variation of yeasts across the subphylum.
Dening v aria tion in yeast cell morphology
Ther e ar e se v er al attributes of the cellular mor phology of yeasts
that vary between species and can be measured across one or
more cell types, including cell shape, cell size, budding type, and
lament production. Individual cell types of each yeast species
typically exhibit one or more distinct shapes (e .g. o void, spherical,
apiculate , and bacilliform). T he cells of different species also differ
in their sizes, whic h ar e described by measuring their length and
width. Cell size av er a ges ar e determined by av er a ging the smallest
and largest lengths and widths recorded.
Yeast species also vary with respect to budding type. In optimal
growth conditions, some species divide during mitosis by budding
at one of the poles of the cell at a time, which is termed unipo-
lar budding. Other species can bud from both poles of the cell,
which is termed bipolar budding. In some species, cell division by
budding can also occur without the use of the poles (i.e. budding
can occur at an y r egion of the cell), which is termed non-polar
or m ultilater al budding. Some species can grow continuously in
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Chavez et al. | 3
(A)
(B)
Figure 2.
Var iat ion in budding yeast cell size and shape in the subphylum Saccharomycotina . (A) For comparison, the cell shape and length of the model
bacterium Esc heric hia coli is also pr ovided (cell sha pe is bacilliform with a cell length av er a ge 1–2 μm). Starmerella bombicola (order Dipodascales ) budding
cell shape is ovoid or elongate with a cell size av er a ge of 3 ×1.5 μm. Kazac hstania transv aalensis (order Sacc harom ycetales ) budding cell shape is allantoid,
apiculate , o void, or ellipsoidal with a cell size av er a ge of 5.25 ×4.25 μm. Trigonopsis variabilis (order Trigonopsidales ) budding cell shape is spherical or
triangular with a cell size av er a ge of 4.45 ×4 μm. Candida albicans (order Serinales ) budding cell shape is spherical or ovoid with a cell size av er a ge of
6 ×4.75 μm. Sacc harom yces cerevisiae (order Sacc harom ycetales ) budding cell shape is spherical or ovoid with a cell size av er a ge of 7.5 ×5.5 μm. Candida
gotoi (order Serinales ) budding cell shape is spherical, ovoid, or elongate with a cell size av er a ge of 5.25 ×5 μm, and can produce hyphae that has an
av er a ge size of 12 ×2.5 μm. Clavispora opuntiae (order Serinales ) budding cell shape is spherical with cell size av er a ge of 9.5 ×3.5 μm. Hanseniaspora
osmophila (order Sacc harom ycodales ) budding cell sha pe is a piculate with cell size av er a ge of 12.7 ×4.75 μm. Candida dubliniensis (order Serinales ) budding
cell shape is apiculate with a cell size average of 7 ×4.9 μm and produces hyphae as large as 22 μm in length. Eremothecium sinecaudum (order
Sacc harom ycetales ) budding cell shape is cylindrical with a cell size average of 16 ×4.5 μm. (B) (i) Ovoid and elongate budding cells of Starmerella
bombicola . (ii) Ellipsoidal budding cells of Kazachstania transvaalensis . (iii) Triangular budding cells exhibited by Trigonopsis variabilis . (iv) Spherical
budding cells exhibited by Candida albicans . (v) Spherical budding cells exhibited by Sacc harom yces cerevisiae . (vi) Tr ue hyphae exhibited by Candida gotoi .
(vii) Spherical budding cells exhibited by Clavispora opuntiae. (viii) Apiculate bipolar budding cell exhibited by Hanseniaspora osmophila . (ix) True hyphae
exhibited by Candida dubliniensis . (x) Cylindrical budding cells exhibited by Eremothecium sinecaudum . Taxonomic type strains are shown, except for S.
cerevisiae S288C. Images i, ii, iii, vi, vii, ix and x were taken from theyeasts.org. Yea st s in images iv , v , and viii were taken by Amanda Hulfac hor gr own at
r oom temper atur e in YPD (yeast extr act, peptone, dextr ose) medium until visible gr o wth w as observed. Size bar = 5 μm.
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4 | FEMS Yea st Resear c h , 2024, Vol. 24
(A)
(B)
Figure 3.
Var iat ion in ascus and ascospore size and shape in the subphylum Sacc harom ycotina . (A) Wic kerhamom yces hampshirensis (order Phaffom ycetales )
ascospor es ar e hat-sha ped and hav e av er a ge sizes of 1.9 ×1.2 μm; asci contain 1–4 ascospor es and their av er a ge size is 6 ×4 μm. Cephaloascus fr agr ans
(order Serinales ) ascospores are hat-shaped and have average sizes of 2.5 ×2.15 μm; asci contain 2–4 ascospores and their average size is 6 ×3.5 μm;
ascospores and asci can be contained inside an ascophore that is stout, tapered, and can be as long as 500 μm. Lipomyces japonicus (order Lipomycetales )
ascospor e sha pe is spherical and av er a ge length is 2.75 μm; asci contain 1–4 ascospor es , ha v e saccate (or sac-like) sha pes , and ha ve an a v er a ge size of
10 ×4.5 μm. Lipomyces oligophaga (order Lipomycetales ) ascospore shape is ellipsoidal and average size of 3.25 ×1.25 μm; asci contain 4 or more
ascopsor es, ar e saccate shaped, and have an av er a ge size of 16.3 ×7.3 μm. Alloascoidea africana (order Alloascoideales ) ascospore cell shape is ellipsoidal
and its av er a ge size is 4.5 ×3.25 μm; asci contains 16–70 ascospor es, ar e ellipsoidal shaped, and their av er a ge size is 30 ×11 μm. Ambrosiozyma
monospora (order Pichiales ) ascospore cell shape is hat-shaped and average size of 7 ×3.5 μm; asci contain 1–2 ascopsores, and are spherical or ovoid in
sha pe. Pac hysolen tannophilus (order Alaninales ) ascospore cell shape is spherical; asci contain up to 4 ascospores; ascospores and asci can be contained
inside an ascophore that is curved, tube-shaped, and can be as long as 60 μm. Metschnikowia hawaiiensis (order Serinales ) ascospore cell shape is
acicular and av er a ge cell length of 160 μm; asci contain 2 ascospor es, ar e wide and tube-shaped, and can be as long as 200 μm. (B) (i) Hat-shaped
ascospores exhibited by Wickerhamomyces hampshirensis . (ii) Spherical ascospores exhibited by Lipomyces japonicus . (iii) Ellipsoidal ascospores exhibited
by Lipomyces oligophaga . (iv) Ellipsoidal ascospores inside a large ascus exhibited by Alloascoidea africana . (v) Hat-shaped ascospores exhibited by
Ambrosiozyma monospora . (vi) Spherical ascospores inside an ascus and tube-shaped ascophore exhibited by Pachysolen tannophilus . (vii) Acicular
ascospore exhibited by Me. hawaiiensis . Taxonomic type strains are shown. Images i, ii, iii, v, and vii were taken from theyeasts.org, and image vi was
ada pted fr om (Kurtzman et al. 2011 ). Ima ge iv was ada pted fr om (Kurtzman and Robnett 2013 ). Size bar = 5 μm.
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Chavez et al. | 5
Figure 4. Cell morphology trait distributions within the subphylum Saccharomycotina . Phylogeny of 332 re presentati ve species of yeasts in the
subphylum Sacc harom ycotina. The phylogen y is from the study by Shen et al. ( 2018 ). The br anc h colors of the phylogeny correspond to the subphylum’s
12 taxonomic orders (Gr oene wald et al. 2023 ). Circles around the phylogeny display variation in select cell morphology traits. From inner to outer
circle: cell length av er a ge (y ello w to blue gr adient); cell sha pe including spherical (pur ple), ovoid (or ange), both spherical and ovoid (gr een), other sha pe
(blue), four or more shape states (red), or absent (white); budding type including unipolar (orange), bipolar (green), multilateral (purple), bipolar and
ssion (blue), ssion (red), or absent (white); lament type including pseudohyphae (blue), true hyphae (orange), both pseudohyphae and true hyphae
(r ed), absent (blac k), or unknown (white); ascus shape including club-shaped (orange), other shape (purple), both club-shaped and other (green), or
absent (white); ascospore shape including spherical (purple), hat-shaped (green), both spherical and hat-shaped (blue), other shape (red), or absent
(white); ascospore number including 1 to 2 (purple), 3 to 4 (orange), 5 to 100 (green), 101 to 200 (blue), 201 to 400 (red), or absent (white). The trait data
values used for the generation of this gure are provided in Ta bl e S1A .
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6 | FEMS Yea st Resear c h , 2024, Vol. 24
the form of laments, which are termed pseudohyphae or true
h yphae. Pseudoh yphae are characterized by the presence of la-
ments composed of chains or clusters of budding cells, while true
hyphae are the result of continuous polarized growth that gener-
ates laments of discrete cells separated by septa (Kurtzman et al.
2011 ).
Ther e ar e a fe w cav eats that ar e important to note regard-
ing the cell morphology of Saccharomycotina species . T he cell mor-
phologies display ed b y y east species can vary b y strain, b y ploidy,
and be inuenced b y gro wth conditions and cell age. For exam-
ple, differ ent cultur e media can induce slight variations in yeast
cell morphologies; formation of pseudohyphae is prominent in
media such as Dalmau plate culture on corn meal agar, but the
same species will have reduced formation of pseudohyphae in
other media such as glucose-yeast extract-peptone (Kurtzman et
al. 2011 ). Tim e of incubation during cell culture can also have
an inuence on cell size, with higher incubation times leading to
larger cell sizes. Cell cycle stage and phase of growth (e.g. lag vs.
stationary phase) can also inuence cell morphology. During the
beginning stages of the cell cycle, a daughter cell is growing and
ther efor e incr easing in size, wher eas at the end of the cell cycle
the parent cell partakes in cellular quiescence in which replica-
tion and growth no longer occur (Sun and Gresham 2021 ). For the
descriptions of cell size av er a ges included in this r e vie w, most of
the measurements were performed after three to ve days of cul-
ture of the taxonomic type strain of each species.
Yea st cells can also undergo meiosis to form and release sex-
ual spores known as ascospores. Although yeast species typically
have both asexual (anamorphic) and sexual (teleomorphic) stages
(Kurtzman et al. 2011 ), a consider able fr action of species are not
known to have a sexual sta ge; for example, se v er al species in the
genera Starmerella of order Dipodascales and Yamadazyma of order
Serinales are not known to produce sexual spores (or ascospores).
To synthesize available information on the variation of cell
morphology of yeasts in the Sacc harom ycotina subphylum, we r e-
trie v ed av ailable data fr om taxonomic descriptions of individual
species from The Yeasts: A Taxonomic Study (Kurtzman et al. 2011 )
and from The Yeasts website ( https:// theyeasts.org/ ), which is the
successor to The Ye as ts : A Taxonomic Study book series. Data were
r etrie v ed for 332 species r ecentl y compiled by the Y1000 + Project
( http:// y1000plus.org/ ) (Hittinger et al. 2015 , Shen et al. 2018 ).
Interspecies v aria tion of cellular morphology
Variat io n in asexual cell shape
Yeast species vary in cell shape within and betw een or ders. Well-
kno wn y easts, such as S. cerevisiae and C. albicans , produce spheri-
cal and ovoid budding cells, while Hanseniaspora uvarum , a species
important to wine pr oduction, pr oduces a piculate sha ped cells.
Examination of a r epr esentativ e set of 332 yeast species (Shen
et al. 2018 ) sho w ed that most budding cells ha ve o void (63.8%
of species or 212/332), spherical (59% or 196/332), and ellipsoidal
(50.6% or 168/332) shapes (note that the numbers do not add up
to 332 because some species exhibit two or more cell shapes). Less
common shapes include elongate (19.6% or 65/332), cylindrical
(19.5% or 65/332), apiculate (3.6% or 12/332), fusiform (1.5% or
5/332), and bacilliform (1.2% or 4/332). Other less common cell
shapes that occur in two to four species include clavate ( Can-
dida orba of order Phaffomycetales , Alloascoidea hylecoeti of order Al-
loascoideales , Cephaloascus albidus and Cephaloascus fr agr ans of or-
der Serinales ), ogival ( Brettanomyces anomalus, Brettanomyces brux-
ellensis, and Brettanomyces custersianus in order Pichiales ), and ac-
uleate ( Candida tammaniensis and Aciculoconidium aculeatum , both
in order Serinales ). Shapes that occur in only one species in our
dataset include triangular ( Trigonopsis variabilis in order Trigonop-
sidales ), r ectangular ( Saproc haete clav ata in order Dipodascales ),
curv ed ( Sporopac h ydermia quercuum in or der Sporopach ydermiales ),
lunate ( Candida golubevii in order Serinales ), and “bowling-pin”
sha ped ( Wic kerhamia uorescens in order Serinales ).
Examination of the distribution of cell shapes across the phy-
logeny of Saccharomycotina suggests that evolutionary relatedness
is not always a good proxy for similarity of cell shape and that
less common cell sha pes ar e spr ead acr oss the phylogen y (Fig. 4
and Table S1 ). For example, the curv ed-sha ped species Sp. quer-
cuum and the bacilliform-shaped species Sporopachydermia lacta-
tivora ar e closel y r elated, wher eas the distantl y r elated Al. hyle-
coeti and Ce. albidus species are both clavate shaped. Similarly,
organisms with cylindrical cell shapes are spread across differ-
ent orders, such as Teunomyces kruisii (order Serinales ) , Eremothe-
cium sinecaudum (order Sacc harom ycetales ) , and Candida boidinii (or-
der Pichiales ); ellipsoidal shaped cells are produced by Kazachsta-
nia aerobia (order Sacc harom ycetales ) and Zygoascus meyerae (order
Dipodascales ); and ta per ed cells ar e pr oduced by Sacc harom ycopsis
malanga (order Ascoideales ) and Wic kerhamom yces hampshirensis (or-
der Phaffomycetales ).
Budding cell shape typically varies between species, but there
is also variation within species. Almost all yeast species exhibit
more than one type of budding cell shape (95.8% or 318/332). For
example, budding cells of Suhomyces canberraensis, of order Seri-
nales , ar e gener all y spherical, but some cells are cylindrical, el-
lipsoidal, or elongate. Species that exhibit four or more different
bud ding shapes mak e up 7.5% of our dataset and are found in
the orders Pichiales , Serinales , Alaninales , Phaffomycetales , Dipodas-
cales , Sacc harom ycetales , and Sacc harom ycodales (Fig. 4 and Table S1 ).
In some cases, this within species variation is conserved between
species; budding cells of the sister taxa Ce. albidus and Ce. fr agr ans
(order Serinales ) can be ovoid, ellipsoidal, or cla vate . Howe v er, other
taxa exhibit a gr eater degr ee of conservation in their cell shape.
For example, the ten species from the genus Debaryomyces (order
Serinales ) included in our dataset exhibit low le v els of cell sha pe
variation since all have mostly spherical and ovoid budding cells.
Similarly, all Hanseniaspora species (order Saccharomycodales ) in our
dataset generate elongated and apiculate shaped cells, likely due
to their specialized budding type (see “Budding type variation”).
Variat io n in sexual cell shape
During sexual r epr oduction, ascomycetous yeast species typically
undergo meiosis to generate ascospores that are enclosed within
an ascus before release for fungal germination (Greig 2009 ). Of
the 332 yeasts examined, 76.9% (230/332) have sexual cycle de-
scriptions; this is likely an underestimate since examination of
their genomes has r e v ealed that 330 of the 332 species exam-
ined contain a mating type locus (Krassowski et al. 2019 ). The 230
yeast species with a known sexual cycle vary in the shape of as-
cospores and asci, as well as in the number of ascospores that
each ascus contains (Figs 3 and 4 ). For example, a few species
including Al. hylecoeti (order Alloascoideales ) and Vanderwaltozyma
polyspora (order Saccharomycetales ) can produce large numbers of
ascospor es ( ∼150–400 ascospor es per ascus in the case of Al.
hylecoeti ), while most other species, such as those within the
gener a Debaryom yces , Hanseniaspora, Kazac hstania, Kluyverom yces,
Lac hancea, Priceom yces, Sacc harom yces , and Torulaspora , pr oduce onl y
one to four ascospores during meiosis . T he a v er a ge number of as-
cospor es pr oduced by species in our dataset is thr ee.
Ascospor es r ange in sha pe and can be spherical, ellipsoidal,
hat-sha ped, Saturn-sha ped, acicular, and aculeate or needle-
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Chavez et al. | 7
sha ped. Hat-sha ped ascospor es occur in 37.4% of species with
a known sexual cycle in our dataset, including in some Ambro-
siozyma (order Pichiales ) , Barnettozyma (order Phaffomycetales ) , and
Hanseniaspora species (order Sacc harom ycodales ), as well as in Bab-
jeviella inositovora (order Serinales ). About 17% of species in our
dataset have spherical ascospores (e.g. Kazachstania species in
order Sacc harom ycetales , Citerom yces matritensis in order Pic hiales,
Starmerella bombicola in order Dipodascales , and se v er al Hanseni-
aspora species in order Sacc harom ycodales ). Debaryom yces species
(order Serinales ) contain spherical ascospores that have a warty
wall phenotype, although species, such as Debaryomyces subglobo-
sus , hav e ascospor es that contain a gear-like structur e. Lipom yces
species (order Lipomycetales ) tend to have uncommon ascospore
sha pes, suc h as cymbiform, which is a shape that appears to be
specic to this genus.
Ther e a ppears to be gr eater v ariation of budding cell shapes
than ascospore shapes within genera or orders. For example,
Metschnikowia species (order Serinales ) exhibit a diversity of bud-
ding cells (e .g. spherical, o void, elongate , ellipsoidal, and cylindri-
cal), but most species produce acicular shaped ascospores . T he
same is true for Eremothecium species (order Sacc harom ycetales ),
whic h ar e known to pr oduce spherical, o void, elongate , ellipsoidal,
and cylindrical budding cells, but their ascospores tend to be elon-
gated and acicular shaped.
Variat io n in asexual cell size
The cell size of the budding cells of different yeast species can
v ary fr om 2.5 ×1 μm in Tort ispora starmeri (order Trigonopsidales )
to as large as 28 ×7 μm in Br. bruxellensis (order Pichiales ) and
Candida tropicalis (order Serinales ) (Fig. 2 ). Ov er all, yeast species
produce budding cells that av er a ge 5.6 μm ×3.6 μm (av er a ge
cell length and width of 332 yeast species across Saccharomy-
cotina ). Ther e ar e species of yeast that hav e lar ge budding cells,
suc h as Nakaseom yces bracarensis (14 ×13.9 μm; order Sacc ha-
romycetales ), and Kurtzmaniella cleridarum (15.8 ×11.1 μm; or-
der Serinales ). Budding cells whose maximum length is larger
than 20 μm occur in species across the orders Serinales , Dipodas-
cales , and Pichiales , including the species Candida parapsilosis (20 ×
8 μm; order Serinales ) , Magnusiomyces tetrasperma (20 ×9 μm; or-
der Dipodascales ) , Kuraishia capsulata (20 ×4 μm; order Pichiales ),
Br. anomalus (22 ×5.5 μm; order Pichiales ) , and Blastobotrys musci-
cola (22 ×2.5 μm; order Dipodascales ) . Species with small budding
cells also occur across the yeast phylogeny. Examples include De-
baryomyces prosopidis (2 ×2.25 μm; order Serinales ) , Ogataea minuta
(2 ×1.8 μm) and Ogataea nonfermentans (2 ×1.8 μm) from order
Pic hiales , and Wic kerhamiella cacticola (2.5 ×1.5 μm), and Zygoascus
ofunaensis (2.05 ×3.45 μm) from order Dipodascales .
The relationship between budding cell size and evolutionary di-
v er gence is unknown, but it appears that similarly sized cells are
mor e likel y to be observ ed between closel y r elated species than
between distantl y r elated ones . For example , budding cells that
are 6 μm length on average (cell width average ranges from 2.5—
5 μm) ar e observ ed in species within the orders Serinales, Trigonop-
sidales , Pichiales , and Saccharomycetales . Ho w ever, average cell size
can sometimes vary considerably between closely related species;
for example, Kazachstania bromeliacearum , Kazachstania kunashiren-
sis, and Kazachstania martiniae (all in order Sacc harom ycetales ) hav e
budding cells that are 3 ×2.5, 5 ×4, and 7.5 ×2.5 μm wide, re-
spectiv el y.
Variat io n in sexual cell size
Asci and ascospor es ar e also highly variable in their sizes
(Fig. 3 ). In some yeast species, a larger ascus can contain
lar ger ascospor es . For example , Metsc hnikowia haw aiiensis and
Metschnikowia bicuspidata (both in order Serinales ) produce large
asci that have a maximum length of 200 μm and 60 μm, re-
spectiv el y, and also contain large ascospores that have a maxi-
mum length of 180 μm long and 50 μm, respectively. Metschnikowia
species contain highly varied asci sizes, but the number of as-
cospor es is conserv ed to one to two per ascus in the genus. In
other cases, a yeast species can generate higher numbers of small
ascospores within a large ascus. For example, Al. hylecoeti (order
Alloascoideales ) and Ascoidea rubescens (order Ascoideales ) produce
asci that can be at maximum as large as 400 μm ×24 μm or 150
×30 μm, r espectiv el y, with ascospor es that ar e 3.2 μm ×2 μm
or 10 ×9 μm, r espectiv el y, suc h that each ascus can produce as
many as 400 ascospores or 150 ascospores, respectively. Ce. fra-
grans (order Serinales ) produces asci that are at maximum 7 μm ×
3 μm and ascospores of 3 μm ×2 μm, making it one of the yeast
species with the smallest asci and ascospores.
Variat io n in budding type
Yea st s can divide by budding in the following ways: utilizing one
cell pole (side), or unipolar; utilizing both cell poles, or bipolar;
and without r el ying on cell polarity, or m ultilater al (Fig. 1 ). Most
species r epr oduce by m ultilater al budding (87.3% of species or
290/332); bipolar yeasts make up 3.9% (13/332), unipolar yeasts
4.5% (15/332), one species that onl y r epr oduces by ssion ( Magnu-
siomyces tetrasperma of order Dipodascales ) and two yeasts that re-
produce by both ssion and bipolar budding ( Nadsonia fulvescens
var. fulvescens and Nadsonia fulvescens var elongata of order Dipo-
dascales ). As discussed pr e viousl y, ther e ar e six species that hav e
not been observed to produce budding cells, and there are 12
species that do not have budding cell information in Kurtzman
et al. ( 2011 ). Unipolar budding is spr ead acr oss the phylogen y of
Sacc harom ycotina yeasts and is found in small numbers of species
within orders Sacc harom ycetales , Serinales , Pichiales , and Dipodas-
cales , whereas bipolar budding is highly conserved in the order
Sacc harom ycodales (Fig. 4 and Table S1 ). Multilateral budding is
also typically conserved, including in all species within the orders
Alaninales , Lipomycetales , Phaffomycetales , and Dipodascales .
Variat io n in lament production
Many yeast species can grow laments in the form of pseudo-
hyphae or true hyphae; sometimes these occur during growth
under stressful conditions (e.g. nutrient limitation, high temper-
ature), but this is not always the case. Not e v ery yeast species
has been observed to generate pseudohyphae or true hyphae; ap-
pr oximatel y 36.7% (131/332) of species are not known to produce
hyphae (Fig. 3 ). Filament morphological diversity is high among
those species that can produce laments, ranging from poorly
de v eloped pseudohyphae (rudimentary and poorly developed) to
highl y br anc hed true hyphae (highl y br anc hed septate). For ex-
ample, 12 species in the genus Kazachstania do not produce hy-
phae or pseudohyphae, while six other species do. Similarly, of the
species included in our dataset, most Barnettozyma species (order
Phaffomycetales ) do not produce laments, except for Barnettozyma
hawaiiensis and Barnettozyma populi, while most Ambrosiozyma (or-
der Pichiales ) and Hanseniaspora (order Saccharomycodales ) species
generate hyphae, except for Ambrosiozyma kashinagicola, Ambro-
siozyma pseudov ander kliftii, Hanseniaspora pseudoguilliermondii , and
Hanseniaspora vineae .
Filament production can vary drastically within orders, even
between closel y r elated species . For example , in the order Seri-
nales , Me. haw aiiensis can pr oduce true hyphae with dark septa,
Metschnikowia cerradonensis produces abundant pseudohyphae,
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8 | FEMS Yea st Resear c h , 2024, Vol. 24
and Metschnikowia hamakuensis can only produce poorly developed
pseudohyphae (Kurtzman et al. 2011 ). Similarly, species within
the genus Blastobotrys (order Dipodascales ) produce various forms
of hyphae; for example, Blastobotrys adeninivorans , Blastobotrys atti-
norum , and Blastobotrys parvus produce true hyphae with distinct
septa, while Blastobotrys aristata, Blastobotrys nivea, and Blastobotrys
proliferans produce true hyphae that are hyaline or tr anspar ent
(von Klopotek 1967 , Sesma and Ramirez 1978 ; Kurtzman and Rob-
nett 2007 ).
The dimensions of pseudohyphae and true hyphae are often
unc har acterized, but data fr om 17 species suggest that the aver-
age width of hyphae is 3.5 μm. The width of hyphae and pseudo-
hyphae ranges from 1 μm in Ce. fr agr ans (order Serinales ) to up to
8 μm in Al. hylecoeti (order Alloascoideales ) . The diameter of hyphae
does not vary as much as the size of other yeast cell types. For
example, the size of budding cells of Ce. albidus and Ce. fr agr ans
(order Serinales ) range from 3 μm to 6 μm but generate hyphae
with diameters of 1 μm to 3 μm.
Conclusions
We have characterized cell morphology traits of a representa-
tive set of 332 species in the subphylum Sacc harom ycotina , whic h
has r e v ealed extensiv e div ersity of cell sha pes and sizes, as well
as budding types and lament production (Kurtzman et al. 2011 ,
Shen et al. 2018 ). Model species of yeasts exhibit cellular morpho-
logical diversity that differs from the typical spherical and ovoid
budding displayed by S. cerevisiae ; their ascospore morphologies
also differ from those observed in S. cerevisiae . Across the yeast
phylogen y, budding cells ar e typicall y r ound (i.e . o void or spher-
ical) with an av er a ge diameter twice the size of a typical bacte-
rial species, such as Escherichia coli (Fig. 2 ). Most yeast species do
not utilize the poles of the cells and instead r epr oduce asexuall y
via m ultilater al budding. Furthermor e, mor e than half of yeasts
can generate pseudohyphae or true septate hyphae . T he sexual
cell morphology of yeasts includes ascospores that are typically
spherical or hat-sha ped, mostl y found in pairs or quartets within
an ascus (Fig. 3 ). The great interspecies diversity is nicely exem-
plied in the cell morphology traits of asexual cell shape and size,
lament production, and sexual cell shape (Fig. 4 and Table S1 ).
An organism will display various cell morphology phenotypes,
whic h ar e likel y r eected in the collectiv e inter actions of pr otein
components and their r elativ e abundances (Chiou et al. 2017 , Bar-
ber et al. 2020 ). Regarding cell morphology, cellular functions, such
as division and r epr oduction, ar e contr olled by the m ultiple path-
ways within the cell polarity network (CPN). In the baker’s yeast
S. cerevisiae , cell polarity is responsible for the localization of pro-
teins to sites of division for successful budding, mating, and l-
ament pr oduction. Highl y conserv ed pr oteins in the CPN include
the GTP ase Cdc42, whic h r ecruits downstr eam pr oteins for polar-
ization at the plasma membrane or can detach following polar-
ization to diffuse fr eel y (Chiou et al. 2017 , Diepe v een et al. 2018 ).
Cell size in S. cerevisiae is closely regulated during the cell cy-
cle phases, with incr eased pr otein abundance of Whi5 correlated
with larger cell sizes (Barber et al. 2020 ). Whi5 phosphorylation
activity is maintained by two CPN proteins, Swi4 and Cln3; ac-
tivation is mediated by Whi3, but how these and other proteins
work together in Sacc harom ycotina yeasts to control cell morphol-
ogy is unknown. Functional relationships between genes can be
r e v ealed by orthologous gene coevolution networks; for example,
coe volutionary anal ysis of ∼2 400 orthologous genes acr oss the
332 Sacc harom ycotina yeasts found that CDC6 , a gene essential for
replication, is connected to 96 other orthologs (Steenwyk et al.
2022 ). Furthermore, the genes that were found to coevolve with
CDC6 acr oss Sacc harom ycotina sho w ed substantial ov erla p with the
genes found to geneticall y inter act with CDC6 in S. cerevisiae (Con-
stanzo et al. 2010 ). An example of budding cell shape that is tightly
associated with budding type occurs in the genus Hanseniaspora,
in which all species reproduce by bipolar budding and exhibit
a piculate-sha ped budding cells. Inter estingl y, most Hanseniaspora
species have lost over 700 genes in comparison to S. cerevisiae , in-
cluding WHI5 and many others involved in the cell cycle (Steen-
wyk et al. 2019 ).
Another a ppr oac h for identifying candidate genes and path-
ways that have likely contributed to variation in yeast cellular
morphology is experimental evolution. Experimental evolution
studies have shown that both new cell morphologies, including
m ulticellular structur es, and consider able differ ences in existing
traits (e.g. cell size) can arise quite rapidly and via diverse mu-
tational r outes (Bozda g et al. 2021 , Farkas et al. 2022 ). Interest-
ingl y, experimental e v olution of S. cerevisiae follo wing the deletion
of genes involved in the CPN can r ecov er quic kl y and r epr oducibl y.
For example, deletion of the gene encoding the CPN protein Bem1
can be rescued by subsequent compensatory mutations in BEM2
and BEM3 , which encode Rho GTPase -activating proteins, after
∼1 000 generations (Laan et al. 2015 ). Future evolutionary experi-
ments that focus on yeast cell morphologies should be performed
to further understand the genetic mechanisms involved in their
generation and evolution.
The cellular morphology of Saccharomycotina asexual and sex-
ual cells is highly diverse, with various patterns observed within
and across its taxonomic orders, but the association of morpho-
logical traits within and between species is not well c har acterized.
For example, as mentioned pr e viousl y, the genus Hanseniaspora
r epr oduce asexuall y by bipolar budding whic h r esults in a picu-
late shaped cells, but it is unknown whether this is due to co-
incidence or whether it reects functional constraints between
the type of budding and specic cell sha pes. Futur e studies of
how the cell morphology network is evolving across yeasts could
benet with studies of association between and within the diver-
sity of asexual cell traits and sexual cell traits of Saccharomycotina
yeasts.
Ac kno wledgements
We thank Marie-Claire Harrison for help with Fig. 4 , members of
the Rokas lab and the Y1000 + Project for helpful discussions and
comments, and Robert A. Sclafani for strain S288C. This material
is based upon work supported by the National Science Foundation
under Grant Nos. DEB-1442148, DEB-2110403, DEB-1442113, and
DEB-2110404; in part by the DOE Great Lakes Bioenergy Research
Center (DOE BER Ofce of Science DE-SC0018409); and the USDA
National Institute of Food and Agriculture (Hatch Projects 1020204
and 7005101). CTH is an H. I. Romnes Facu lty Fellow, supported by
the Ofce of the Vi ce Chancellor for Research and Graduate Edu-
cation with funding from the Wisconsin Alumni Research Foun-
dation. MARC Scholar G.K. is supported by a grant from the Na-
tional Institute of General Medical Sciences of the National Insti-
tutes of Health: T34 GM136451. Research in AR’s lab is also sup-
ported by the National Institutes of Health/National Institute of
Allergy and Infectious Diseases (R01 AI153356), and the Burroughs
Wellcome Fund.
Supplementary data
Supplementary data is available at FEMSYR Journal online.
Downloaded from https://academic.oup.com/femsyr/article/doi/10.1093/femsyr/foad055/7492805 by guest on 23 January 2024

Chavez et al. | 9
Conict of interest : Antonis Rokas is a scientic consultant for LifeM-
ine Ther a peutics, Inc.
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Recei v ed 7 Mar c h 2023; revised 4 November 2023; accepted 22 December 2023
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