transcription factors in fungi

M I N I R E V I E W

Transcription factors in fungiEkaterina Shelest

Department of Molecular and Applied Microbiology, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoll Institute (HKI),

Jena, Germany

Correspondence: Ekaterina Shelest,

Department of Molecular and Applied

Microbiology, Leibniz Institute for Natural

Product Research and Infection Biology, Hans

Knoll Institute (HKI), Beutenbergstrasse 11a,

07745, Jena, Germany. Tel.: 149 3641

5321114; fax: 149 3641 5320808; e-mail:

[email protected]

Received 3 June 2008; accepted 30 June 2008.

First published online August 2008.

DOI:10.1111/j.1574-6968.2008.01293.x

Editor: Derek Sullivan

Keywords

transcription factor; DNA-binding domain;

fungal-specific; horizontal gene transfer.

Abstract

Transcription factors (TFs) orchestrate gene expression control of a cell and, in

many respects, their repertoire determines the life and functionality of the cell. For

a better understanding of their regulatory mechanisms, it is essential to know the

entire repertoire of TFs of a species. The increasing number of sequenced genomes

together with the development of computational methods allow us not only to

predict whole sets of TFs but also to analyse and compare them. Such an analysis is

required in particular for fungal species, as our knowledge of the potential set of

TFs in fungi is very limited. In fact, at present we do not know which TFs can in

general be found in fungi, and which of them are strictly fungal specific. Other

interesting questions regard the evolutionary relationships of fungal TFs with

other kingdoms and the functions of fungal-specific TFs. This minireview

addresses these issues. The analysis of predicted occurrences of DNA-binding

domains in 62 fungal genomes reveals a set of 37 potential ‘fungal’ TF families. Six

families are fungal-specific, i.e. they do not appear in other kingdoms. Interest-

ingly, the fungal-specific TFs are not restricted to strictly fungal-specific functions.

Consideration of fungal TF distributions in different kingdoms provides a

platform to discuss the evolution of domains and TFs.

Introduction

Transcription factors (TFs) are essential players in the signal

transduction pathways, being the last link between signal

flow and target genes expression. The functionality of TFs

depends on many parameters, and their involvement in a

particular signalling pathway is sometimes difficult to pre-

dict. Nonetheless, the mere occurrence of a specific TF type

can already provide some information about the possible

existence of particular signalling pathways, or, in the oppo-

site case, the absence of a certain TF can be taken to indicate

that the corresponding pathway is absent. Therefore, it

would be beneficial to know the whole repertoire of TFs in

different species and in higher taxa. There are some taxon-

specific TFs, for instance those that are found only in

bacteria or in plants, or in animals, but little is known about

fungal TFs and their relatedness to TFs in other eukaryotes.

The number of experimentally verified TFs in fungi is

significantly lower than in higher eukaryotes, as reflected in

databases such as TRANSFAC (Wingender et al., 2000) and

MycoPath (both: http://www.biobase-international.com/

pages/). This can have two possible explanations: either they

are really less abundant (which would conform to the view

that organisms require additional TFs as their complexity

increases; Amoutzias et al., 2007) or they have not yet been

identified. However, we can estimate the number of poten-

tial TFs computationally, by pairwise comparisons (align-

ments, BLAST searches) or by hidden Markov models

(HMMs) and other models based on multiple alignments

of domains (Wilson et al., 2008). Large evolutionary dis-

tances, which characterize the fungal kingdom (Dujon et al.,

2004), make the application of usual (pairwise) comparative

approaches unreliable; thus, HMMs are the better choice. By

considering the HMM-based predictions from correspond-

ing databases we can estimate the possible number of fungal

TFs and list those TF families (TFfs) that can potentially

occur in fungi.

Thus far, we do not have functional verification of each

and every TF of a particular species (including those that are

very well annotated, such as human, mouse or Saccharo-

myces cerevisiae). Thus, the analysis of an entire set of TFs

cannot be based totally on experimental data. Here, I analyse

only the predictions, intentionally considering from the

start all known DNA-binding domains, independently of

FEMS Microbiol Lett 286 (2008) 145–151 c�Hans Knoll InstituteJournal compilation c� 2008 Federation of European Microbiological Societies

Published by Blackwell Publishing Ltd

their initial taxonomic assignment. The underlying idea is

that as we do not know which TFs occur in fungi, it is

reasonable simply to check them all. This gives information

not only about potential fungal TFs, but also about the

sharing of TFs between kingdoms.

At present, we lack an overview of TFs in fungi, and in

fact we do not have answers to several simple questions:

which TFs can be found in fungi, and which cannot? How

many TFs (or TFfs) are strictly fungal-specific? With which

other species do fungi share their TFs? Here I address these

questions and also discuss some evolutionary insights that

arise from the consideration of TF taxon distributions.

Data sources and methodologicalbackground

Besides literature sources, here I analyse data from the DBD

database (Wilson et al., 2008), a database of predicted

sequence-specific DNA-binding TFs for all publicly available

proteomes. The method behind DBD uses profile HMMs of

DNA-binding domains [taken from the PFAM (protein

family) and Superfamily databases] to predict transcription

factors by homology. The advantage of this method is that it

can accurately identify both known and previously unchar-

acterized TFs that bind specifically to DNA; even TFs with-

out obvious sequence homology to known factors can be

identified. Therefore, DBD provides far more information

than manually curated literature-based databases such as

TRANSFAC, although with the drawback of possible false

predictions.

The Superfamily database (Madera et al., 2004) is based

on the structural classification of proteins (SCOP) (Murzin

et al., 1995). SCOP is a structural domain-based hierarchical

classification with several levels, including the ‘superfamily’.

Proteins grouped together at the superfamily level are

defined as displaying structural, functional and sequence

evidence of common evolutionary ancestry. The ‘family’ level

lies below this and groups more closely related domains. This

level is described by PFAM, a well-known collection of

protein families and domains (Bateman et al., 2004).

To collect fungal TFfs, I screened all DNA-binding

domains from DBD (‘Browse Families’) for the entry ‘Fungi’

in the ‘Taxonomic distribution’. Ultimately, the ‘Taxonomic

distribution’ links to the corresponding PFAM and Super-

family taxonomic tables, which can be downloaded and are

easy to examine. A family was considered as ‘fungal’ if it

occurred in more than three species, as single occurrences

are more likely to be false predictions. The latter statement

has been checked: every protein of a TFf, represented in

fewer than three fungal species, was examined for the level of

similarity with its counterparts from other kingdoms (by

BLAST). There were seven TFfs with low occurrence, each

represented in fungi by one to three proteins. In all cases the

percentage of identity was low (c. 30%), so they were

considered as false predictions.

Analysis of the cross-kingdom distributions was made

only on the family level. For each fungal TFf the correspond-

ing ‘Species distribution’ table of PFAM was examined,

noting only the presence (‘yes’ or ‘no’) in animals, plants,

bacteria and viruses. Here, again, the single occurrences (in

fewer than three species) were considered as nonreliable.

There are 62 fungal genomes in the DBD database, the

majority of which belong to the Ascomycetes. Nonetheless,

there are about 10 species of Basidiomycetes and several

genomes of other fungi. Thus, the representativeness of the

set is satisfactory for the current purposes.

Which transcription factors can beexpected in fungi?

The ‘fungal’ TFfs were collected as described in the previous

section and are detailed in Table 1. There is some redun-

dancy between the Superfamily and PFAM lists, when the

names of a family and a superfamily are the same (SRF,

HLH, etc.). Families are normally subdivisions of the super-

families, so the appearance of the same term on either level

is justified. If a family and a superfamily completely coin-

cide, I consider only one of them further. For fungal TFfs,

superfamilies are essentially equal to families (coincide

in 4 90% of instances) for helix–loop–helix (HLH),

SRF-like and Zn2/Cys6 (zinc cluster).

Superfamilies of DNA-binding domains presentin fungi

The total number of superfamilies of DNA-binding domains

is 37 (http://supfam.org/SUPERFAMILY), of which only 12

are predicted in fungi (Table 1). From these 12 super-

families, three are not found in other kingdoms: ‘Zn-cluster’,

‘Zinc domain conserved in yeast copper-regulated transcrip-

tion factors’ and ‘DNA-binding domain of Mlu1-box-bind-

ing protein MBP1’.

PFAM families

PFAM contains 296 entries for the term ‘DNA-binding’.

After text-mining-based filtering for sequence-specific bind-

ing, i.e. excluding general TFs, nonspecific binding and

domains involved in other processes (reparation, recombi-

nation, etc.), 145 domains remain. Of these, 37 (about one-

quarter) domains are found in fungal species. Thus, the

proportion of ‘fungal’ TFfs in PFAM families and ‘Super-

families’ is roughly the same.

Which TF families are fungal-specific?

Three superfamilies and three families of TFs are fungal-

specific, i.e. they are present only in fungi and are not found

FEMS Microbiol Lett 286 (2008) 145–151c�Hans Knoll InstituteJournal compilation c� 2008 Federation of European Microbiological SocietiesPublished by Blackwell Publishing Ltd

146 E. Shelest

in other kingdoms (Table 2). Here I consider them and their

functions in more detail.

The largest class of fungal-specific domains is the zinc-

cluster superfamily [this can also be found in PFAM as a

family (PF00172)]. The DNA-binding domain consists of

six cysteine residues that, unlike the other zinc-finger

proteins, bind two zinc atoms; thus, this domain can also

be found under the names Zn(II)2Cys6, or zinc binuclear

cluster. The zinc clusters can interact with DNA as mono-

mers or as homo- or heterodimers. It is a multifunctional

class of factors that regulate a plethora of cellular processes,

including the most crucial for survival and prospering of the

fungus: sugar and amino acid metabolism, gluconeogenesis

and respiration, vitamin synthesis, cell cycle, chromatin

remodelling, nitrogen utilization, peroxisome proliferation,

pleiotropic drug response and stress response (reviewed in

MacPherson et al., 2006). Many zinc cluster TFs have more

than one distinct role, and can also have overlapping

functions. Several dozens of zinc cluster proteins have been

experimentally proven in S. cerevisiae, Candida albicans,

Schizosaccharomyces pombe, as well as in several Aspergillus

species and other filamentous fungi.

Unlike the multifunctional zinc cluster, the representa-

tives of the two other fungal-specific superfamilies (‘DNA-

binding domain of MBP1’ and ‘copper-regulated Zinc

domain’) are more restricted in their functions. Factors with

the ‘DNA-binding domain of MBP1’ are involved in cell-

cycle regulation (Ayte et al., 1997, Machado et al., 1997).

MBP1, together with Swi6, comprises a complex MCB-

binding factor (MBF), a TF from budding yeast that binds

to the so-called MCB (MluI cell-cycle box) elements found

in the promoters of many DNA synthesis genes and activates

their transcription at the G1 ! S phase transition (Xu et al.,

1997). The MBP1 DNA-binding domain has some topolo-

gical similarity to the ‘winged helix’ DNA-binding domain

(SCOP, http://scop.mrc-lmb.cam.ac.uk/scop/index.html).

The ‘Zinc domain of yeast copper-regulated factors’

regulate transcription of a set of yeast genes, many of which

encode membrane proteins (Keller et al., 2001) and mediate

copper utilization and stress response (Jungmann et al.,

1993). The functions of different zinc copper-regulated TFs

can be independent and complementary: for instance, Ace1

and Mac1 undergo reciprocal copper metalloregulation in

yeast cells (Keller et al., 2005). As indicated by its name, this

family is often referred to as yeast-specific; nonetheless, it is

possible to predict its representatives in all fungal species

considered.

The second largest TF class after the zinc cluster is the

‘fungal-specific transcription factor domain’ (Fungal_trans,

PF04082). Interestingly, in all experimentally proven factors

listed in the TRANSFAC database, the Fungal_trans domain

is always located downstream of the zinc cluster domain (the

zinc cluster tends to locate near the N-terminus). The

Table 1. Twelve superfamilies and 37 PFAM families of TF DNA-binding

domains, predicted to occur in fungal species

Family name Database ID

PFAM family PFAM ID

APSES domain PF02292

bZIP TF 1 PF00170

Basic region leucine zipper 2 PF07716

TFIIH C1-like domain PF07975

CCAAT-binding TF (CBF-B/NF-YA) subunit B PF02045

CP2 TF PF04516

DDT domain PF02791

Putative FMN-binding domain PF04299

Fork head domain PF00250

Fungal-specific TF domain PF04082

Fungal Zn(2)-Cys(6) binuclear cluster domain PF00172

GATA zinc finger PF00320

GRF zinc finger PF06839

Helix–loop–helix DNA-binding domain PF00010

Homeobox domain PF00046

HSF-type DNA-binding PF00447

Helix–turn–helix PF01381

Bacterial regulatory HTH proteins, AraC family PF00165

Helix–turn–helix, Psq domain PF05225

Mating-type protein MAT a1 PF04769

MIZ zinc finger PF02891

Myb-like DNA-binding domain PF00249

NDT80/PhoG-like DNA-binding family PF05224

NF-X1-type zinc finger PF01422

CCR4-Not complex component, Not1 PF04054

PAS fold PF00989

RFX DNA-binding domain PF02257

SART-1 family PF03343

SGT1 protein PF07093

SRF-type TF (DNA-binding and dimerization domain) PF00319

STE-like TF PF02200

TEA/ATTS domain family PF01285

YL1 nuclear protein PF05764

BED zinc finger PF02892

Zinc finger, C2H2 type PF00096

Zinc finger, C5HC2 type PF02928

Zinc knuckle PF00098

Superfamily Superfamily

ID

C2H2 and C2HC zinc fingers 57667

DNA-binding domain of Mlu1-box-binding protein

MBP1

54616

Glucocorticoid receptor-like (DNA-binding domain) 57716

Helix–loop–helix DNA-binding domain 47459

Homeodomain-like 46689

Lambda repressor-like NA-binding domains 47413

Nucleic acid-binding proteins 50249

p53-like transcription factors 49417

SRF-like 55455

Winged helix DNA-binding domain 46785

Zinc domain conserved in yeast copper-regulated TFs 57879

Zn2/Cys6 DNA-binding domain 57701



147Transcription factors in fungi

domain is also predicted in proteins without a zinc cluster

domain (InterPro), but these predictions have not been

confirmed experimentally. Thus, it remains questionable

whether the Fungal_trans domain can act independently.

There is also no single literature reference concerning the

functional characterization of this domain so, although the

domain is clearly present in many functionally characterized

TFs, its own role remains obscure. Factors having this

domain are involved in sugar metabolism, amino acid

metabolism, gluconeogenesis and respiration, fatty acid

catabolism, etc (TRANSFAC, PFAM).

The APSES domain is a sequence-specific DNA-binding

domain that can be modelled as a basic HLH (bHLH)-like

structure (Dutton et al., 1997). APSES proteins (ASM-1,

Phd1, StuA, EFGTF-1 and Sok2) represent a conserved class

of fungal TFs regulating cellular differentiation in ascomy-

cetes. They are involved in regulation of morphogenesis and

metabolism in yeast (Doedt et al., 2004), developmental

complexity in filamentous fungi (Dutton et al., 1997),

regulation of the cell cycle (Whitehall et al., 1999) and

reversible yeast–hyphal transitions (Wang & Szaniszlo,

2007). Moreover, some APSES proteins may be involved in

determining virulence [shown for Efg1p of C. albicans (Lo

et al., 1997)]. APSES proteins might act both as activators

and repressors of gene expression, because they stimulate

reversible transitions between spherical and filamentous

cells (Doedt et al., 2004).

The MAT a 1 family includes S. cerevisiae mating type

protein a 1. It activates mating-type a-specific genes with

the help of the MADS-box-containing MCM1 transcription

factor. They bind cooperatively to PQ elements, common

sequence motifs in the upstream regions of a-specific genes

(Sengupta & Cochran, 1991). a 1 interacts in vivo with

STE12, linking expression of a-specific genes to the

a-pheromone response pathway; STE12 interaction is species-

specific (no interaction with Kluyveromyces lactis STE12)

(Mukai et al., 1993; Yuan et al., 1993).

As it can be seen from Table 2, the number of associated

functions correlates with the mean occurrence of corre-

sponding genes (last column). This suggests that these TFs

are quite function-specific.

It would be logical to expect that fungal-specific TFs exert

fungal-specific functions. This holds true for APSES and

MAT a1 [APSES proteins apparently have general functions,

which are not specific for fungi (e.g. regulation of cell cycle),

but these functions are achieved through regulation of

fungal-specific morphogenetic processes]. The functions of

other fungal-specific TFfs remain quite ubiquitous. The

question of why these functions have been delivered to

highly taxon-specific genes requires further investigation.

Taxonomic distributions of fungal TFfsand some insights into domain evolution

I now focus on those TFfs that occur in fungal species but

are not restricted to them. For simplicity, I will refer to them

as ‘fungal TFfs’. I analysed the distribution of such TFfs

across the four kingdoms: animals, plants, bacteria and

Table 2. Fungal-specific TFfs and their functions

Name

Database and

accession no. Function Reference(s)

Mean

occurrence�

Zn2/Cys6 (Zn cluster) Superfamily,

57701

Sugar and amino acid metabolism,

gluconeogenesis, respiration, vitamin synthesis,

cell cycle, chromatin remodelling, nitrogen

utilization, peroxisome proliferation, drug

resistance, stress response

MacPherson et al. (2006) 11

DNA-binding domain of

Mlu1-box-binding

protein MBP1

Superfamily,

54616

Cell cycle Ayte et al. (1997), Machado et al.

(1997)

0.6

Zinc domain conserved

in yeast copper-

regulated TFs

Superfamily,

57879

Copper utilization and stress response Jungmann et al. (1993), Keller et al.

(2001, 2005)

0.2

Fungal-specific

transcription factor

domain

PFAM, PF04082 Sugar metabolism, amino acid metabolism,

gluconeogenesis, respiration, fatty acid

catabolism, nitrate assimilation, etc.

TRANSFAC, PFAM 4.2

APSES PFAM, PF02292 Morphogenesis and metabolism, developmental

complexity, yeast–hyphal transitions, cell cycle

Dutton et al. (1997), Whitehall et al.

(1999), Doedt et al. (2004), Wang &

Szaniszlo (2007)

0.5

MAT a 1 PFAM, PF04769 Activation of mating-type a-specific genes Tatchell et al. (1981), Sengupta &

Cochran (1991)

0.06

Thirty-five species were considered for the calculation of mean occurrences. MAT a 1 was found in 21 species, DNA-binding domain of MBP1 in 32

species, and the remainder were present in all 35 species.�Mean occurrences are given per species per 103 proteins.


148 E. Shelest

viruses. Most of the fungal TFfs are eukaryotic, and some are

ubiquitous (spread over all kingdoms). The most-interest-

ing cases from an evolutionary point of view are those where

a fungal TFf is shared either with bacteria or with viruses

(Table 3). I will consider these in more detail.

There are five domain families that are found in eukar-

yotes and in viruses, but not in bacteria. The first two classes,

bZIP domains, belong to one of the second largest families

of dimerizing TFs, and are normally referred to as eukar-

yotic. The high degree of functional conservation of the

bZIP proteins highlights the ancient origin of this class of

TFs. These domains are also predicted in viruses, although

in very few species. Remarkably, they occur only in herpes-

virus and retroviruses, which might indicate that they have

been recruited by the viruses from the hosts. A similar

situation can be observed for HLH domain family and zinc

fingers (zf), only HLH domains are predicted in more

divergent virus species. The occurrence and functionality of

these TFs in viruses has to be confirmed experimentally,

after which it would be interesting to speculate on their

origin. The evolution of bZIP, bHLH and ZF domains in

eukaryotes has been investigated (e.g. Deppmann et al.,

2006; Landais et al., 2006; Amoutzias et al., 2007), but the

question of the viral domains has not been raised.

There is only one eukaryotic TFf, HTH_psq, representa-

tives of which are found in animals, fungi and bacteria. The

distribution of the family is rather broad in animals. In

fungi, it occurs in the evolutionarily divergent Ascomycota

and Basidiomycota. The domain is also predicted in several

distantly related bacterial species. Thus, it is difficult to

define the origin of the domain without detailed phyloge-

netic sequence analysis.

A more interesting situation is seen when the domains are

shared only between fungi and bacteria (FMN_bind_2 and

HTH_AraC). Both domains are referred to as ‘bacterial’ in

PFAM and the number of occurrences confirms this state-

ment: HTH_AraC is found in 13 fungal (all ascomycetes)

and 598 bacterial species, and FMN_bind_2 is found in 19

fungal and 130 bacterial species. Both types of domain-

containing proteins are quite conserved in fungal species

(80–90% similarity), although the level of overall protein

similarity to the bacterial proteins is modest (around

40–50%). The functionality of the fungal genes has not yet

been proven experimentally (as is also the case for the vast

majority of the bacterial FMN_bind_2 and HTH_AraC-

containing proteins). Nonetheless, the occurrence of such

highly conserved genes, possessing a binding domain and

exhibiting reasonable similarity to their bacterial counter-

parts, cannot be coincidental. It is logical to suppose that

these domains have been acquired from bacteria by means of

horizontal gene transfer. Whether or not they retain the

regulatory function requires further investigation.

The other way that fungal TFs may evolve is via capture of

viral domains. An example of such a process is provided by

the APSES domain, which appears to have evolved through

the capture of a viral KilA-N-like precursor early in fungal

evolution (Iyer et al., 2002).

Discussion and conclusions

A specific repertoire of TFs is partly the result of adaptive

evolution. The more signalling pathways and regulatory

networks a species can exploit, the more flexible can be its

reaction to disturbance. By contrast, there should be a

balance between the number of pathways and the robustness

of the response, which are, obviously, not in linear depen-

dence. Finally, successful adaptation can be achieved

through various evolutionary scenarios, which are now

reflected by the specific sets of TFs. New TFs can be gained

in different ways, including duplication with following

mutations, or horizontal gene transfer. With regard to the

future of the signalling pathways, gain of TFs may have two

important evolutionary consequences: (1) delegation of the

functions of ‘old’ TFs to new TFs, and (2) gaining new

functionality together with the new TFs (probably leading to

the appearance of new regulatory networks). Investigation

and comparison of the TF sets can help us to reconstruct the

evolutionary history of the signalling pathways. Knowing

the specific repertoire of TFs has more practical conse-

quences: for instance, it allows us to make a preselection of

corresponding positional weight matrices (PWMs) for pro-

moter analysis. Sometimes it may be even more useful to

know not which TFs are present in a species but which are

Table 3. Fungal DNA-binding domains in different taxa

Kingdoms Shared domains

Fungi1animals1plants1viruses bZIP_1 (bZIP transcription factor 1,

PF00170)

bZIP_2 (Basic region leucine zipper

2, PF07716)

zf-GRF (GRF zinc finger, PF07716)

bHLH (Helix–loop–helix DNA-

binding domain, PF00010)

ZF-C2H2 (Zinc finger, C2H2 type,

PF00096)

Fungi1animals1bacteria HTH_psq (Helix–turn–helix, Psq

domain, PF05225)

Fungi1bacteria FMN _bind_2 (Putative FMN-

binding domain, PF04299)

HTH_AraC (Bacterial regulatory HTH

proteins, AraC family, PF00165)

Four kingdoms (animals, plants, bacteria and viruses) were screened for

fungal domains. Besides the purely eukaryotic TFs (not shown), three

groups of fungal TFs were shared by eukaryotes either with viruses or

with bacteria.




lacking. This enables a researcher to exclude some potential

pathways from consideration, thus saving time. By contrast,

if it is known that a particular pathway takes place and the

corresponding TF does not occur in the genome, it is

challenging to identify an alternative TF.

The first step in identification of specific TF sets for

fungal species is to confine the set of those TFs that can in

general be found in fungi.

This minireview lists for the first time all TFfs that are

predicted to occur in fungi. There is no specific database for

fungal TFs so far.

Only about one-quarter of known DNA-binding domains

of TFs can be predicted to occur in fungi. This observation is

in agreement with the suggestion that the complexity of an

organism correlates with an increase in both the absolute

number of TF genes and the proportion of TFs in a genome

(Levine & Tjian, 2003; Amoutzias et al., 2007). In total, fungi

have 37 domains and domain families, assigned to 12

superfamilies. Three superfamilies and three families are

fungal-specific.

Most of the fungal-specific TFfs are not restricted to

strictly fungal-specific functions, at least not on the level of

domain families. This means that some of the general

functions that are fulfilled in other kingdoms by other TFs

have been transferred at some moment of evolution to

fungal-specific TFs. The reasons, mechanisms and conse-

quences of this transfer (which could be the result of

convergent evolution of TFs in different kingdoms) are of

great interest and require further investigation.

Analysis of taxonomic distributions gives us some insight

into the evolution of TFs in general and their evolution in

fungal species in particular. There are indications that

several eukaryotic domains could have been acquired by

viruses (in particular retroviruses). The two bacterial do-

mains (FMN_bind_2 and HTH_AraC) are highly conserved

in fungi and could have been horizontally transferred to

fungal genomes.

Acknowledgements

I would like to thank Edgar Wingender, Reinhard Guthke,

Daniela Albrecht and especially Anthony Pugsley for critical

reading and useful comments on the manuscript.

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