Archaea and the origin of eukaryotes

13 Pages·2017·0.66 MB·English

by  Laura Eme

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Archaea and the origin of eukaryotes
Laura Eme, Anja Spang, Jonathan Lombard, Courtney W. Stairs and Thijs J. G. Ettema
Abstract | Woese and Fox’s 1977 paper on the discovery of the Archaea triggered a revolution in
the field of evolutionary biology by showing that life was divided into not only prokaryotes and
eukaryotes. Rather, they revealed that prokaryotes comprise two distinct types of organisms, the
Bacteria and the Archaea. In subsequent years, molecular phylogenetic analyses indicated that
eukaryotes and the Archaea represent sister groups in the tree of life. During the genomic era,
it became evident that eukaryotic cells possess a mixture of archaeal and bacterial features in
addition to eukaryotic-specific features. Although it has been generally accepted for some time
that mitochondria descend from endosymbiotic alphaproteobacteria, the precise evolutionary
relationship between eukaryotes and archaea has continued to be a subject of debate. In this
Review, we outline a brief history of the changing shape of the tree of life and examine how the
recent discovery of a myriad of diverse archaeal lineages has changed our understanding of
the evolutionary relationships between the three domains of life and the origin of eukaryotes.
Furthermore, we revisit central questions regarding the process of eukaryogenesis and discuss
what can currently be inferred about the evolutionary transition from the first to the last
eukaryotic common ancestor.
Sister groups
Two descendants that split The pioneering work by Carl Woese and colleagues In this Review, we discuss how culture- independent
from the same node; the revealed that all cellular life could be divided into three genomics has transformed our understanding of
descendants are each other’s major evolutionary lines (also called domains): the archaeal diversity and how this has influenced our
closest relative. Eukarya (or eukaryotes), the Bacteria and the Archaea1,2 understanding of the topology of the tree of life.
(FIG. 1). In the late 1980s, phylogenetic trees that were Specifically, we discuss how the discovery of novel
Monophyletic groups
A monophyletic group is a constructed on the basis of ancient gene duplications archaeal superphyla combined with improved molec-
group of organisms that forms provided the first strong evidence that eukaryotes ular phylogenetic approaches has led to unprecedented
a clade, which consists of all and archaea were sister groups2,3. This tree topology is insights into eukaryogenesis — the processes by which
the descendants of a common
generally referred to as the three-domains tree of life eukaryotic cells evolved from prokaryotic precursors.
ancestor.
(FIG. 1a). The discovery of several molecular features We outline the main questions that need to be addressed
Eukaryogenesis that are shared between only archaea and eukaryotes to understand the process of eukaryogenesis, provide
The whole sequence of appeared consistent with this rooting of the tree of life. details on how archaeal research has allowed us to start
evolutionary events occurring
For example, archaeal RNA polymerases were found to answering some of these questions and highlight future
between the first eukaryotic
be more complex than their bacterial counterparts, and research priorities.
common ancestor (FECA) and
the last eukaryotic common their subunit composition was found to resemble that of
ancestor (LECA) explaining the eukaryotes4,5. However, the proposed evolutionary rela- Uncovering archaeal diversity
process by which eukaryotic tionship between monophyletic groups of the Eukarya and In the 1990s, the advent of DNA sequencing in molec-
cells evolved from prokaryotic
the Archaea has been challenged. The three-dimensional ular phylogenetics enabled the analysis of various genes
ancestors.
structures of ribosomes and a shared amino acid inser- (or markers) to investigate the evolutionary relationships
tion in a conserved region of the elongation factor 1α between major branches in the tree of life. Initially, these
Department of Cell and homologues indicated that eukaryotes are a sister group analyses were limited to a small number of genes that
Molecular Biology, Science of the ‘eocyte archaea’ (that is, Crenarchaeota)6,7. In other had been sequenced from a limited number of cultivated
for Life Laboratory, Uppsala
words, these analyses supported the idea that eukaryotes organisms, and for a long time, the Crenarchaeota and
University, Box 596,
Uppsala SE‑75123, Sweden. emerged from within the Archaea, which would be in the Euryarchaeota were the only recognized archaeal
Correspondence to T.J.G.E. favour of a two-domains tree of life. In this evolution- phyla. These analyses, together with the simpler phylo-
[email protected] ary scenario, Archaea and Bacteria represent the only genetic methods and evolutionary models that were
primary domains of life, and eukaryotes later emerged available at the time, yielded conflicting results, and
doi:10.1038/nrmicro.2017.133
Published online 10 Nov 2017 from lineages within these groups (FIG. 1b). the relationships among the domains of life remained
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a b
Crenarchaeota Crenarchaeota
Eukarya
Euryarchaeota
Euryarchaeota
Bacteria Eukarya Bacteria
c d
TACK Verstraetearchaeota Lokiarchaeota Asgard
TACK Crenarchaeota Geoarchaeota
‘Korarchaeota’ Crenarchaeota Thorarchaeota
‘Korarchaeota’ Odinarchaeota
Thaumarchaeota Eukarya Bathyarchaeota Heimdallarchaeota
‘Aigarchaeota’ Thaumarchaeota
Eukarya
‘Aigarchaeota’
Euryarchaeota Euryarchaeota
Bacteria
Bacteria DPANN
Figure 1 | Evolution of the tree of life. A schematic representation of our understanding of the relationships between
Nature Reviews | Microbiology
eukaryotes and archaea over the past 40 years. In a three-domains tree of life (part a), Archaea and Eukarya each represent
a monophyletic group and share a unique common ancestor to the exclusion of Bacteria2,3. By contrast, a two-domain tree
of life was proposed early on, and the topology of this tree has undergone several changes. When the Archaea was
thought to consist of the Euryarchaeota and the Crenarchaeota phyla only (part b), several kinds of molecular evidence
supported the close relationship of eukaryotes and Crenarchaeota6,7. In the early 2010s, eukaryotes were found to branch
within, or as sister to, the Thaumarchaeota, Aigarchaeota, Crenarchaeota and Korarchaeota (TACK) superphylum25,28–32
(part c). Phylogenomic analyses that included members of the Asgard superphylum strongly suggested that eukaryotes
originated from within the Asgard archaea or that they represented a sister group to them47,52 (part d). Bacteria and
Eukarya are indicated in light purple and red, respectively, whereas green and blue represent archaeal lineages. Domain
and superphylum rank-level names are bolded or italicized, respectively. Names of proposed phyla are in quotation marks.
Note that the Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota and Nanohaloarchaeota (DPANN) lineage
is represented as a monophyletic lineage, although this is a topic of debate155,156.
Metagenomics
The sequencing of genetic the subject of intense debate8–14. However, during the past During recent years, newly developed m etagenomics
material extracted directly two decades, advances in DNA sequencing technologies approaches, such as genome-resolved metagenomics, have
from environmental samples.
and cultivation-independent genomic approaches have revealed additional phyla belonging to the TACK
Genome-resolved provided genomic data from new archaeal lineages that superphylum, including the Bathyarchaeota35–37, the
metagenomics are distantly related to the cultivated Crenarchaeota and Geoarchaeota38,39 and the Verstraetearchaeota40 (FIG. 2).
The assembly of complete or Euryarchaeota. Their discovery has substantially extended Other studies have revealed a variety of archaeal lin-
draft genomes exclusively from
our knowledge of the diversity, evolution, metabolic capa- eages whose members often have small cells and small
metagenomic sequencing data.
bilities and ecological impact of archaea. These genomic genomes, and have been proposed to form a deep-
DPANN approaches first allowed the genome sequencing of rep- branching superphylum called DPANN (Diapherotrites,
A proposed archaeal resentatives of several phylum-level archaeal lineages: the Parvarchaeota, Aenigmarchaeota, Nanoarchaeota and
superphylum comprising proposed phylum Korarchaeota15–18 and, more recently, Nanohaloarchaeota)41–44. In addition to these proposed
Diapherotrites, Parvarchaeota,
the ammonia-oxidizing Thaumarchaeota19–23 and their new archaeal phyla, several euryarchaeal lineages have
Aenigmarchaeota,
Nanohaloarchaeota and sister phylum, the proposed phylum Aigarchaeota24. also been identified45,46.
Nanoarchaeota. More recently, Together, Thaumarchaeota, Aigarchaeota, Crenarchaeota Another newly discovered phylum-level lineage is the
it was suggested that and Korarchaeota (TACK) were found to form a mono- Lokiarchaeota47. These organisms were identified from
additional candidate phyla phyletic group referred to as the TACK superphylum25,26 marine sediments that were sampled near Loki’s Castle
such as Woesearchaeota,
(or the Proteoarchaeota27; FIG. 2). The use of phylog enomic (a field of five hydrothermal vents that are located in the
Pacearchaeota, Micrarchaeota
and possibly Altiarchaeales are approaches combined with improved models of sequence middle of the Atlantic Ocean between Greenland and
part of this group. evolution and broader taxon sampling (BOX 1) yielded Norway)48. Initial sequencing surveys of these samples
support for the two-domains tree of life25,28–34, in which revealed that ~10% of the 16S ribosomal RNA (rRNA)
Hydrothermal vents
eukaryotes initially appeared to branch from within the genes belonged to the Deep Sea Archaeal Group (or
Areas of the sea floor from
which geothermally heated Archaea, specifically within or as sister group to the TACK Marine Benthic Group B). This clade had been previ-
water issues. superphylum (FIG. 1c). ously hypothesized to represent an unexplored lineage
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Crenarchaeota
es
al
b
THSCG ‘Korarchaeota’ selaccocoru Sulfolo hermoproteales Geoarchaeota Lokiarchaeota
THSCG flu T
se 'Verstraete-
D
archaeota'
Thorarchaeota Heimdallarchaeota (AAG)
Thaumarchaeota
Heimdallarchaeota
(MHVG)
MHVG
MBGA
Odinarchaeota
Nitrosocaldales
Group I.1.b
Bathyarchaeota
100
95–99
‘Aigarchaeota’ 90–94
Group I.1.a 85–89
Group C3
16S rRNA genes
from genomes
0.2 substitutions
per site
Figure 2 | Genomic exploration of TACK and Asgard archaeal diversity. The tree represents our current understanding
Nature Reviews | Microbiology
of the diversity of Thaumarchaeota, Aigarchaeota, Crenarchaeota and Korarchaeota (TACK) archaea (in blue) and Asgard
archaea (in green) based on 16S ribosomal RNA (rRNA) gene sequencing surveys. Clades for which genomic data are
available are indicated by red branches and dots. All other lineages are known from 16S rRNA gene sequences only.
The phylogeny was reconstructed from 16S rRNA genes of TACK and Asgard archaea (1,471 positions) in a maximum-
likelihood framework by use of IQ-TREE157 and the GTR + F0 + G model of sequence evolution. All 16S rRNA sequences
>1,000 bp that were assigned to TACK and Asgard lineages were retrieved from the Silva rRNA database and clustered at
95% identity with the Cluster Database at High Identity with Tolerance (cd-hit) software158. Ultrafast bootstrap statistical
support values for branches corresponding to major clades are indicated by circles in different shades of grey according
to the figure label. The scale bar indicates the number of substitutions per site. Names of proposed phyla are in quotation
marks. AAG, Ancient Archaeal Group; MBGA, Marine Benthic Group A; MHVG, Marine Hydrothermal Vent Group;
THSCG, Terrestrial Hot Spring Crenarchaeotic Group. Modified with permission from REF. 45, Science/AAAS.
of the TACK archaea25, making it a lineage of potential suggesting that Lokiarchaeota represent a deep-
importance regarding the origin of eukaryotes. After fur- branching Euryarchaeota-related lineage50, although
ther metagenomic analyses, a near-complete genome was this work was itself questioned51. However, in support
reconstructed for Lokiarchaeum sp. GC14_75, and partial of the two-domains tree of life scenario, another recent
genomes were reconstructed for two l ow-abundance and study identified eight additional representatives from
distantly related organisms (Loki2 and Loki3). three novel phyla that are related to Lokiarchaeota
The discovery of the Lokiarchaeota has provided (that is, the Odinarchaeota, Thorarchaeota and
additional evidence for the two-domains tree of life Heimdallarchaeota)52. Collectively, these new archaeal
because at the time of discovery, it was shown to con- lineages represent the Asgard superphylum, and phylo-
tain the closest relatives of eukaryotes in phylo genomic genomic analyses have confirmed that they are closely
Eukaryotic signature analyses. Moreover, members of Lokiarchaeota related to eukaryotes47,52 (FIG. 1d). Furthermore, in-depth
proteins were found to carry genes encoding proteins that were analyses of the Asgard archaea genomes confirmed
(ESPs). Proteins involved in
assumed to be specific to eukaryotes47 (often called the presence of ESPs, which belong to protein families
key eukaryotic processes and
conserved across most eukaryotic signature proteins, or ESPs49). A recent study that represent building blocks that are fundamental for
eukaryotic diversity. has challenged this view of the tree of life, alternatively eukaryotic cellular complexity.
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Box 1 | The difficulty of inferring ancient evolutionary relationships of all extant eukaryotes, that is, the youngest ancestor of
all living eukaryotes (FIG. 3). It is important to note that
The past two decades have seen substantial changes in molecular phylogenetic even though all eukaryotes living today descend from
approaches. Of importance has been the transition from analysing individual genes to
LECA, not all descendants of LECA will have survived
reconstructing phylogenies that are based on ‘supermatrices’ of concatenated gene
to date (FIG. 3). In fact, it is well recognized that several
or protein sequences, up to several thousand. However, when trying to disentangle
mass extinctions have affected eukaryotic biodiversity
ancient evolutionary events, such as the relationships between the three domains of
long after the existence of LECA53. FECA is defined as
life, one is confronted with several persistent problems. First, the phylogenetic signal
reflecting deep relationships is usually weak because it erodes over time: the more time the oldest ancestor whose only living descendants are
has passed since the event of interest, the more nucleotide substitutions can occur eukaryotes. Similarly, it is possible (and most likely)
multiple times at a given site in the sequence. Second, tree reconstruction artefacts (for that many other now-extinct lineages descended from
example, due to functional shifts, compositional bias and evolutionary rate variation FECA, which did not have any eukaryotic features
across sites and branches139) are usually greater at this evolutionary timescale. Although (FIG. 3). FECA thus represents the first generation after
the former can, in theory, be overcome through the analysis of a large number of the divergence from its closest prokaryotic relatives
markers, in reality, studies aiming to resolve the relationships between Archaea,
that do not have any descendants that exist today other
Bacteria and Eukarya have been constrained to using a fairly small set of genes that are
than eukaryotes. As these organisms are phylogenetic
conserved in the three domains of life. Several enhancements in phylogenomic analyses
entities, we do not need to know what kind of cellu-
have helped to overcome this ‘phylogenomic impasse’ (REF. 9). For example,
lar, genetic and metabolic features they had in order
phylogenetic models, implemented in either maximum-likelihood or Bayesian
frameworks, have been improved to better fit the evolution of molecular sequence to be able to identify their precise position in the tree
data. These improvements include taking into account the heterogeneity of of life. However, it is important to keep in mind that
composition across sites140 or across time34,141. Another conceptual change proposed to LECA and FECA are moving targets; as we discover
resolve the tree of life has been to analyse not only universal markers (such as ribosomal a broader diversity of organisms, both the branching
proteins) but also different sets of carefully selected non-universal gene sets in order to points (nodes) in the tree of life corresponding to
resolve specific parts of the tree (for example, the position of the root of archaea)32,142. LECA and FECA and our inferences about their bio-
The recent increase in the characterization of novel microbial genomes43,44,47,52,143–145
logical properties will change (FIG. 3). The discovery of
has led to major breakthroughs in resolving deep splits in the tree of life. Improved
the Asgard archaea is an example of this. Before their
taxonomic sampling minimizes phylogenetic reconstruction artefacts through a better
discovery, some evolutionary scenarios suggested that
estimation of the substitution process, which is crucial for resolving difficult
eukaryotes were a sister group to the TACK archaea,
phylogenetic questions139.
and FECA was virtually indistinguishable from the last
common ancestor of the TACK archaea and eukaryotes
Although the discovery of these novel archaeal (FIG. 3). Now that the Asgard archaea are known to be
lineages has provided important insights into the ori- the closest archaeal relatives of eukaryotes that have
gin of eukaryotes, it has also raised new questions. been identified to date, FECA is inferred to be essen-
In particular, the exact position of eukaryotes in the tially identical to the last common ancestor of Asgard
tree of life with respect to the Asgard archaea remains archaea and eukaryotes. This suggests that the evolu-
unresolved to date. To identify the precise position of tionary gap that exists between FECA and LECA will
eukary otes within the tree of life, obtaining genomic decrease only if we discover closer archaeal relatives
data from broader taxonomic archaeal lineages is cru- of eukaryotes and/or ‘deeper-branching’ eukaryotic
cial. Excitingly, such efforts might be achievable, because lineages (FIG. 3). Consequently, the series of evolution-
phylogenetic analyses of environmental 16S rRNA gene ary events that are thought to have occurred during
sequences indicate that the currently available genomic eukaryogenesis (that is, in the time between FECA
data for Asgard archaea represent only a small fraction and LECA) will also have to be revised accordingly.
of the existing diversity (FIG. 2). It is important to keep in mind that as we discover
new lineages that branch between the current FECA
The archaeal ancestry of eukaryotes and LECA, and whose phenotypes may not resemble
Eukaryogenesis: the matter of definitions. An evolu- model archaea and eukaryotes, decisions will have to
tionary link between Asgard archaea and eukaryotes be made regarding the classification of new organisms
has numerous implications for our understanding of to determine whether they will be considered archaea
the process of eukaryogenesis. However, the literature or eukaryotes (FIG. 3).
on this subject can sometimes be confusing owing to In this framework, investigating eukaryogenesis
the use of terms that are not always explicitly defined involves answering the following questions: which fea-
and may have different meanings. The term, eukaryo- tures were present in LECA? When did these features
First eukaryotic common genesis, is generally used to refer broadly to the evo- emerge? How many of these features originated auto-
ancestor lutionary events that occurred during the emergence genously between FECA and LECA and how many were
(FECA). The most ancient
of the eukaryotic cell from its prokaryotic ancestor(s). inherited from their prokaryotic ancestor(s)? Which
organism whose only living
In this Review, we refer to eukaryogenesis as the prokaryotic partners participated in eukaryogenesis?
descendants are present-day
eukaryotes. whole sequence of evolutionary events that occurred What does this allow us to infer about FECA? In the
between the existence of the first eukaryotic common following sections, we address these questions in detail.
Last eukaryotic common ancestor (FECA) and the existence of the last e ukaryotic
ancestor
common ancestor (LECA). Both of these organisms, What do we currently know about LECA? Phylogenomic
(LECA). The most recent
ancestor of all present-day or perhaps populations, are defined solely by phylo- and comparative genomic analyses have led to
eukaryotes. genetic criteria. LECA is the last common ancestor the hypothesis that LECA, estimated to have lived
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Other archaea TACK archaea Asgard archaea Eukarya
LECA
Time
FECA
Figure 3 | Key time points in eukaryogenesis. Several evolutionary time points relevant to the discussions about
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eukaryogenesis are represented on a schematic unrooted tree of archaea and eukaryotes. The white oval and square
represent the last eukaryotic common ancestor (LECA) and the first eukaryotic common ancestor (FECA), respectively.
The grey oval highlights that LECA would represent a more ancient organism if an early diverging eukaryotic lineage was
discovered (right-hand dashed line), whereas the grey square shows that FECA can be pushed forward in time only if we
discover an archaeal lineage that is closer to eukaryotes (left-hand dashed line). The hatched square signifies where FECA
was placed before the discovery of Asgard archaea. Grey branches depict extinct lineages. The triple line at the base of
Asgard archaea illustrates that their monophyly is still unclear and that eukaryotes might branch within them. Note that
lineages diverging between FECA and LECA (extinct or extant) will arbitrarily be considered an archaeon or a deeply
diverging eukaryote on the basis of phenotypic criteria that remain to be universally accepted; this is illustrated by the
lineages without a coloured background.
~1–1.9 million years ago54, already was a fully fledged or facultatively aerobic, mitochondria72 that descended
eukaryote and possessed a large number of features that from a once free-living alphaproteobacterium73–75. It is
are uniquely found in modern eukaryotes55,56. This organ- clear that these organelles had a respiratory electron
ism possessed the eponymous feature of the eukaryotes: transport chain that generated ATP in the presence of
the nucleus, including nuclear pores and associated com- oxygen. However, the presence or absence of anaerobic
plexes, and nuclear lamina55,57. This nucleus is believed metabolism in LECA is still intensely debated76,77.
to have contained linear chromosomes with telomeres, Despite the consensus in the field on the presence
encoding ~4,000 genes58,59 containing spliceosomal of these features in LECA, it is important to keep in
introns60. LECA is thought to have possessed complex mind that many of these inferences are based solely on
gene expression regulatory mechanisms, including the presence of (some of) these components in diverse
Telomeres an RNAi system59 and small non-coding RNAs61, and eukaryotic lineages and the assumption that they were
Repetitive nucleotide
chromatin that existed in different states dependent on vertically inherited. It is worth noting that several of
sequences located at the ends
of the linear chromosomes of histone packaging55. Transcription was uncoupled from these features are absent in various extant, and often
most eukaryotic organisms. translation and involved extensive RNA processing distantly related, eukaryotic lineages. This implies that
(including intron splicing, capping and polyadenyla- present-day eukaryotes share very few universal char-
Spliceosomal introns tion)62. This ancestor also had an elaborate protein regu- acteristics but instead contain a collection of defining
Introns in the nuclear
lation and recycling system composed of a proteasome features that are not, or are rarely, found in prokary-
protein-coding genes of
eukaryotes that are removed and a ubiquitin s ignalling system63. otes78,79; each eukaryotic organism harbours a large sub-
by spliceosomes. The cellular environment of LECA was highly com- set of typically eukaryotic features but rarely all of these
partmentalized through the presence of a sophisticated features. By inferring the existence of the entirety of
Proteasome
endomembrane system55,64,65 composed of the endo- these sometimes sparsely distributed characteristics in
A large protein complex
responsible for regulated plasmic reticulum, the Golgi apparatus, endosomes, LECA, we are contemplating an ancestor that appears to
degradation of proteins as part lysosomes and peroxisomes; this organism possessed be substantially more complex than most of its descend-
of the ubiquitin system found exocytic and endocytic pathways (including phagocyto- ants; this implies that there were important changes in
in all eukaryotes.
sis). A modern actin-based and tubulin-based cytoskele- evolutionary trends before and after LECA (that is,
ton and associated molecular motor proteins55 enabled complexification and simplification, respectively)78.
Horizontal gene transfer
(HGT). Exchange of genetic intracellular trafficking, cell motility and a complex In light of this, several additional factors need to be
material between cells and/or cell cycle66,67, including meiosis68. Additionally, LECA taken into consideration. First, and as previously sug-
organisms; sometimes called was likely able to synthesize phospholipids composed gested78, the role of horizontal gene transfer (HGT) in the
lateral gene transfer. This
of glycerol 3-phosphate and fatty acids69, as well as the evolution of eukaryotes is likely to be more influential
contrasts with the vertical
inheritance of DNA from sterols70 and sphingolipids71 characteristic of present-day than what is currently assumed, especially HGT between
parent to offspring. eukaryotes (BOX 2). LECA was also the host of aerobic, unicellular eukaryotes80–83. HGT allows several distant
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Box 2 | The membrane anomaly that only a minority of the genes that were present in
LECA (~4,000)58,59 were inherited from prokaryotic
All cells are bound by lipid membranes, of which phospholipids are the main ancestors. Among these, the main phylogenetic signal can
components. However, archaeal phospholipids are made up of isoprenoids and sn-glycerol- be traced back more often to bacteria (56–71%)88,90 than
1-phosphate (G1P) instead of the conventional fatty acid-based and sn-glycerol-3-
to archaea (18–37%)87,90. Genes with a bacterial ances-
phosphate (G3P)-based phospholipids that are found in bacteria and eukaryotes69.
try are overwhelmingly linked to metabolic processes,
Although this apparent lipid divide had a historical role in the acknowledgement of
whereas archaeal genes tend to be involved in informa-
Archaea as a separate domain of life1,146, it has now become one of the main challenges
when considering different eukaryogenesis scenarios: if the eukaryotic host lineage tion processing87–90. However, tracing the identity of
originated from within archaea, how did the bacterial-like eukaryotic phospholipids the bacterial or archaeal donor lineages has been more
evolve147? This is not just a matter of lipid chemistry; it also has important implications in challenging. Consistent with the alphaproteobacterial
the evolution of many essential membrane proteins that had to adapt to a completely origin of mitochondria73–75, the most common bacte-
new membrane environment throughout the lipid transition106. rial sister lineage to eukaryotic genes in phylogenies is
Some eukaryogenesis scenarios suggest that the phospholipid transfer from the that of alphaproteobacteria. Nonetheless, this repre-
bacterial ancestor of mitochondria to the host facilitated the lipid shift, either before
sents only a minority of the total number of eukaryotic
or after the endosymbiotic event148,149. When the first Lokiarchaeum metagenome
genes of prokaryotic ancestry (5.6–8.5%)88,89. By con-
became available, it was shown to lack the homologues of both the G1P and G3P
trast, phylogenetic studies of other gene families have
dehydrogenases while containing putative mechanisms to metabolize G3P, isoprenoids
revealed a sister relationship between various specific
and fatty acids. Therefore, lokiarchaeal phospholipids were initially suggested to have a
mixed intermediate composition150. Although appealing, this hypothesis is weakened bacterial lineages and eukaryotes. There are several
by the discovery of genes that encode G1P dehydrogenase homologues in genomes of explanations for this. First, single-gene phylogenies
other Asgard archaea. can display artefactual topologies in phylogenetic trees
However, we are still limited by the scarcity of information on lipid biosynthesis owing to several causes, most notably the limited evo-
pathways in archaea151. For instance, several archaea have been postulated to have the lutionary signal that can be extracted from their charac-
capacity to synthesize fatty acids152,153 and G3P as components of phospholipids150,154, teristically short sequences (BOX 1). In fact, when branch
but this has never been confirmed. Further experimental efforts to test these
statistical support for any given tree topology is taken
hypotheses, combined with further comparative genomic analyses as more archaeal
into account88, only a few gene phylogenies strongly
genomes become available, will undoubtedly provide us with new opportunities to
support a sister relationship between eukaryotes and
tackle these questions.
non- alphaproteobacterial bacteria. Second, it has
been argued that LECA genes of bacterial origin were
descendant lineages to exhibit similar features that were acquired with the mitochondrial ancestor and that the
not necessarily present in their last common ancestor; phylogenetic signal linking many of these genes to vari-
ignoring this mechanism leads to an inevitable overesti- ous non-alphaproteobacterial ancestors was the result
mation of the gene content in LECA. Yet, although it has of continuous HGT between prokaryotic lineages89
certainly led to the acquisition of a number of individual (FIG. 4). By contrast, another study suggests that genes
enzymes and their accessory proteins, it is less likely of origins other than alphaproteobacteria were acquired
that HGT has heavily influenced the evolutionary his- before the mitochondrial endosymbiosis, reflecting
tory of complex molecular systems84. Second, although either several symbiotic associations or gradual waves
uni cellular organisms represent most of the eukary- of HGT into the host genome90 (FIG. 4). Similarly, in all
otic diversity, genome sequence data from those major these studies87–90, genes of archaeal descent in eukary-
microbial eukaryotic groups remain sparse85. Where otes grouped with Euryarchaeota as often as they did
these data do exist, they are heavily biased towards par- with TACK archaea lineages91. Although this may be
asitic organisms with reduced genomes. This can lead because of the low resolution of relationships between
to the misconception that genomic streamlining is the sequences that is typically found in single-gene trees
dominant mode of evolution in eukaryotes86. Finally, (BOX 1), it is also likely that the absence of genomic
as lineages diverge and adapt to different niches, ances- data from Asgard archaea in these analyses prevented
tral genes that are no longer essential for viability of the the detection of a clear signal from the host lineage.
organism will be lost, whereas other genes that were Likewise, given the past and current debates over the
not present in their ancestor(s) will be gained. When identity of the closest alphaproteobacterial relative of
accounting for these different evolutionary mechanisms mitochondria92–101, it is conceivable that this (possibly
during the analysis of genomic data, one does not need deep-branching) lineage has yet to be discovered and
to invoke a dramatic change in gene number or mode that its absence from current phylo genetic reconstruc-
Genomic streamlining
A form of genome evolution of evolution before and after LECA. tions prevents the precise determination of genes of
that occurs through size mitochondrial origin.
reduction and simplification Which features of LECA were inherited from prokary­ Furthermore, it should also be considered that some
in terms of gene content;
otic ancestors? Establishing which features of LECA LECA genes of putative bacterial origin were already
particularly common among
were inherited from prokaryotes and the identity of present in the archaeal ancestor, following ancient HGTs
parasitic organisms.
these prokaryotic ancestors is crucial to understand- from bacteria. Supporting this idea, genomes of Asgard
Phylogenetic signal ing eukaryogenesis. Several phylogeny-based analyses archaea appear to contain a large number of genes of
Information contained in have tried to define the subset of LECA genes with a bacterial origin47,52 (FIG. 4). Finally, some of these bacte-
homologous molecular
prokaryotic origin87–90. Although these studies vary rial genes that are sparsely distributed across the tree of
sequences used to reconstruct
the historical relationships widely in the estimated number of LECA gene families eukaryotes might have been absent in LECA. Instead,
between the sequences. of prokaryotic descent (~550–1,100), they still suggest they may have been acquired more recently by HGT
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are involved in anaerobic energy metabolism, which
Bacteria-to-
Genes of bacterial archaea HGT are found in many eukaryotic microorganisms that
origin acquired experience hypoxia76 (FIG. 4).
by HGT Regardless of the relative contribution of each of
FECA these evolutionary scenarios to the observed phylo-
Gene loss genetic patterns, it is important to distinguish cellular
ancestors from genetic ancestors. Whereas the latter
Gene of archaeal can describe any prokaryotic lineage that contributed
origin to some of the genetic material of LECA by HGT, the
Alphaproteobacterium
Gene of alpha- former refers to a prokaryotic lineage whose only exist-
proteobacterial
ing descendants are eukaryotes. Given current evi-
origin
Gene of Bacteria-to- Bacteria-to- dence, there are only two presumed cellular ancestors
cyanobacterial pre-LECA alphaproteobacteria of eukaryotes: the archaeal lineage whose descendant
origin HGT HGT was the putative host of the mitochondrial endosym-
biosis and the alphaproteobacterial ancestor of mito-
chondria. Traditionally, the evolutionary events that
occurred during eukaryogenesis are mapped on a line
running from the archaeal host to LECA. Although
this may appear to be arbitrary, it reflects the idea that
LECA many eukaryotic features could have developed in the
host lineage before the acquisition of the mitochondrial
Nucleus Bacteria-to-
endosymbiont (see below).
Bacteria-to-eukaryotes cyanobacteria
HGT and eukaryotes- HGT
to-eukaryotes HGT The relative timing of the emergence of LECA features.
Many hypotheses have been proposed to explain the ori-
Cyanobacterium gin of eukaryotes72,102–105. With the discovery of Asgard
archaea and the additional evidence that the eukaryotic
lineage emerged from within Archaea47,52, a number of
these models can now be excluded106,107. Nonetheless,
accepting that Bacteria and Archaea were the two pri-
mary domains of life does not solve the debate over
the relative timing of emergence of the features that
were present in LECA. In particular, controversy per-
sists in the field regarding the timing and the influence
of mitochondrial endosymbiosis, that is, about how
much time passed and which evolutionary innovations
occurred between the divergence from archaea and the
Extant eukaryotes mitochondrial acquisition. Autogenous or ‘mito-late’
models108 assume that endosymbiosis occurred in a
Figure 4 | Evolutionary scenarios for the origins of bacterial genes in eukaryotes.
Within eukaryotic genomes, most genes of bacterial origin cNanantuorte b Ree tvraiecweds b| Macikc robiology proto-eukaryotic host, that is, an organism that already
to alphaproteobacterial (mitochondrial, yellow) or cyanobacterial (plastid, green) possessed many eukaryotic cellular features (for exam-
ancestors. These genes could derive from horizontal gene transfer (HGT) into the ple, the nucleus, a dynamic cytoskeleton and a sophis-
alphaproteobacterial or cyanobacterial ancestors of organelles (pink and dark green stars, ticated endomembrane system); these features are often
respectively) before their endosymbiosis. Other bacterial genes could have been considered to be essential prerequisites in such models
transferred into the eukaryotic lineage before or after the mitochondrial endosymbiosis to explain the engulfment of the alphaproteobacterial
(blue stars) or after the diversification of eukaryotes (black stars) and propagated among ancestor of mitochondria through phagocytosis. By
eukaryotes by eukaryote-to-eukaryote HGT. Some bacterial genes were probably acquired
contrast, other hypotheses109,110, generally referred to
before the first eukaryotic common ancestor (FECA) and were already present in the
as symbiogenic or ‘mito-early’ models, postulate that
archaeal ancestor of eukaryotes (dark red stars). Outgoing lines indicate lineage-specific
mitochondrial endosymbiosis took place very early dur-
gene losses after the existence of the last eukaryotic common ancestor (LECA). These have
ing eukaryogenesis and has been the driving force that
likely affected genes of all origins; for clarity, only examples affecting genes of bacterial
origin are shown. These various evolutionary events are not mutually exclusive, and a has led to the evolutionary innovations between FECA
debate lies in their relative importance (see main text). As most genes of endosymbiotic and LECA. The absence of amitochondriate organisms
origins have been transferred to the nucleus before LECA, they are depicted in the nucleus among living eukaryotes (with one currently known
only; organelles are shown without DNA for simplicity. Circles represent genes of archaeal, exception, resulting from a secondary loss111) is often
alphaproteobacterial and cyanobacterial origins. Filled stars represent laterally acquired used as an argument against mito-late hypotheses. It
genes. Empty stars represent losses of laterally acquired genes. has been argued that this is evidence for mitochondrial
endosymbiosis being the first and the most impor-
from a bacterial donor to a eukaryotic lineage and sub- tant event that drove eukaryogenesis. However, this
sequently transferred between eukaryotic organisms. hypothesis fails to account for the fact that no living
For example, this has been one of the proposed evo- eukaryote has been observed to possess an evolutionary
lutionary scenarios regarding the origin of genes that inter mediate form of any of the multitude of complex
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features that emerged between FECA and LECA. It is was identified in Heimdallarchaeota52. Interestingly,
difficult to conceive that the entirety of eukaryotic cel- homologues of some eukaryotic RNA poly merase com-
lular complexification and the origination of thousands ponents are uniquely found in only some TACK and
of genes took place so rapidly that no speciation events Asgard lineages22,24,52,117; they have likely been lost in
occurred between FECA and LECA (FIG. 3). A more other lineages after divergence from their last common
likely explanation is that these evolutionary intermedi- ancestor (FIG. 5).
ates did exist but did not leave any living descendants. Although the proteasome has long been thought to
In addition, eukaryotic microorganisms have not been have an archaeal origin118, homologous components
studied to the same extent as multicellular eukaryotes, of the eukaryotic ubiquitin modifier system were dis-
and, although perhaps unlikely, we cannot exclude the covered only recently in archaea. Bona fide ubiquitins
possibility that deep-branching eukaryotes with inter- and potential ubiquitin-interacting proteins such as E1
mediate forms of some cellular features do exist but ubiquitin-activating enzymes were first identified in
have thus far escaped identification. ‘Candidatus Caldiarchaeum subterraneum’, a member
Owing to the absence of known intermediate lin- of the proposed phylum Aigarchaeota, whose genome
eages that lack some features of LECA, inferring the was found to encode a functional eukaryotic-like E1–
rela tive timing of emergence of these characteristics has ubiquitin- conjugating enzyme (E2)–(RING) ubiquitin
proven difficult. A recent study aimed to estimate the ligase (E3) ubiquitylation cascade24,119. Ubiquitin-related
relative age of the mitochondrial endosymbiosis event modifier 1, which is involved in protein modifica-
by utilizing phylogenetic distances between eukaryotic tion in eukaryotes, has been described in only a few
proteins and their prokaryotic homologues as a proxy Crenarchaeota120, but preliminary analyses indicate that
for divergence times90. The authors observed shorter this protein is present in Bathyarchaeota and Asgard
evolutionary distances between alphaproteobacteria- archaea as well (A.S. and T.J.G.E., unpublished obser-
derived proteins and their bacterial counterparts than vations). These observations are consistent with the dis-
between LECA proteins of other bacterial and archaeal covery of all major components of the ubiquitin modi fier
origins; this was interpreted as evidence for a moder- system in most representatives of these lineages47,52
ately late acquisition of mitochondria by a host that (FIG. 5). In Asgard archaea, these proteins are encoded
already contained bacteria-derived and archaea- derived by conserved gene clusters, which in some organisms
protein families. The results of this study have fuelled are adjacent to genes encoding components of the endo-
considerable debate112,113. Even if these conclusions are somal complex required for transport (ESCRT) machin-
correct114, we are left with few insights into the timing ery (see below). Altogether, these findings indicate that
of the emergence of all the genes and associated features FECA already harboured a sophisticated ubiqui tin
that have no recognizable prokaryotic homologues, modi fier system, which may have had a function in
which represent the vast majority of the gene content protein targeting and degradation, perhaps by using a
of LECA. pathway mediated by a n ESCRT-like machinery121.
Actin and tubulin represent the basic units of micro-
The nature of the last common ancestor of Asgard filaments and microtubules, key components of the
archaea and eukaryotes. Although determining the eukaryotic cytoskeleton, and they both belong to large
order of events in eukaryogenesis is difficult, defin- protein families. Members of these superfamilies are
ing the gene content of the last common ancestor of present in almost all prokaryotic cells; however, the
Asgard archaea and eukaryotes is more feasible. When precise origin of the eukaryotic cytoskeleton (either
attempting to reconstruct the gene content of this from Bacteria or Archaea) could not be inferred until
common ancestor, it is crucial to keep in mind that recently122. Additional members of these superfamilies,
extant Asgard archaea diverged from this ancestor as more closely related to their eukaryotic counterparts,
long ago as extant eukaryotes did. All the features of have now been identified in archaea (FIG. 5). Distant
the Asgard–eukaryotic common ancestor are therefore homologues of actins (that is, crenactins) were shown
unlikely to have been conserved in all its living archaeal to be present in Korarchaeota, Crenarchaeota and
descendants115. In light of this, the patchy distribution of Aigarchaeota and were found to assemble into actin-like
ESPs across different archaeal lineages (FIG. 5) is perhaps filaments123–126. Subsequently, analyses of the genomes
less surprising. of some members of the Thaumarchaeota revealed
The first features that were traced back to the archaeal distant tubulin homologues (that is, ar-tubulins)127.
ancestor of eukaryotes included components of the Detailed analyses of Asgard archaea genomes helped
DNA replication, transcription and translation machin- to identify the origin of several eukaryotic cytoskele-
eries, as well as those of the proteasome, exosome and tal components47,52. All Asgard archaea possess vari-
a ubiquitin modifier system116. Subsequent analyses of ous bona fide actin-related proteins, which are more
TACK and Asgard archaea genomes have revealed addi- closely related to eukaryotic actins than to archaeal
tional components of these systems. The presence of homologues. Furthermore, these genomes encode
homologues of the eukaryotic ribosomal proteins L22e homologues of eukaryotic profilin and gelsolin domain
and L28e in the genomes of Asgard archaea47,52 suggests proteins, which are key regulators of actin filament
that these archaea carry genes for the most eukaryote- dynamics. Finally, Odinarchaeota carry genes for tubu-
like ribosomes that have been identified thus far. In lin homologues that are considerably more similar to
addition, a homologue of a putative DNA polymerase-ε eukaryotic tubulins than previously described archaeal
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Ribosomal proteins Informational Trafficking machinery Cytoskeleton Ubiquitin system
proteins
46 78 45 L41eL14eL34eL8aeS25eS30eL13eL38eL22eL28e ELF1RNA pol *αRPB8 or RpoGRPC34TOPOIBDNA pol ε ESCRT-I: VPS28‡ESCRT-I: steadiness box domainESCRT-II: EAP30 domainESCRT-II: VPS25§ESCRT-III: VPS2/24/46§ESCRT-III: VPS20/32/60Roadblock/LC7TRAPP domain proteinSEC23 and SEC24Arrestin domain proteinWD40-Armadillo gene cluster ¶ActinARP 2/3 complex, subunit 4ProfilinGelsolin domain protein#Tubulin Ubiquitin-related modifier 1Ubiquitin domain proteinUb-activating protein E1Ub-conjugating protein E2Putative E3UFM1 domain (Ub-like protein)Putative deubiquitin protein
3 9 3 7 Eukarya 1 2 3 4 5 6 7 8 9 10 1 2 3 4 5 6 1 2 3 4 5 6 7 8 9 1011 1 2 3 4 5 1 2 3 4 5 6 7
9 5 2 10 2 6
8 4 4 10 6 1 11 1 5 Lokiarchaeota
7 3 3 Odinarchaeota
6 2 2
Thorarchaeota
5 1 5 1
Heimdallarchaeota
4
3 Verstraetearchaeota
2
Crenarchaeota
1
‘Korarchaeota’
Bathyarchaeota
‘Aigarchaeota’
Thaumarchaeota
Euryarchaeota
Figure 5 | Origins of eukaryotic signature proteins present in FECA. This figure indicates the presence of
homologues of eukaryotic signature proteins (ESPs) in various archaeal lineages (filled circNleast)u, raes Rweevlile aws st h| eMiric irnofebriorelodg y
time of emergence along the schematic tree of Archaea. The origin of each ESP is indicated on a schematic tree of life
(left-hand side). Owing to the involvement of ESPs in often complex structures, and sometimes even in informational
processes, our inferences assume that they were vertically inherited84. This would be in line with recent analyses
suggesting that during archaeal evolution, the majority of genetic transmission events appear to be vertical rather
than horizontal142. Eukaryotes and Asgard archaea are shown as a multifurcation (the occurrence of several branches
splitting in the tree from the same point) because their relationships are not yet clearly resolved. Diapherotrites,
Parvarchaeota, Aenigmarchaeota, Nanoarchaeota and Nanohaloarchaeota (DPANN) archaea are not represented
because of the current uncertainty regarding their phylogenetic placement. Names of proposed phyla are in quotation
marks. *Light shading indicates the presence of RNA polymerase A homologues encoded by two separate genes,
whereas dark shading indicates single subunit homologues, similar to what is found in eukaryotes. ‡Putative
homologues are lightly shaded. §Vps2/24/46 and Vps20/32/60 represent paralogous protein families belonging to the
endosomal complex required for transport (ESCRT)-III. In contrast to other archaea, Asgard archaea genomes encode
homologues of both families. ¶Light shades indicate distant actin homologues (that is, crenactin). #Light shades indicate
distant tubulin homologues (that is, ar-tubulins). Ub, ubiquitin. Modified and expanded with permission from
REFS 47,52, Macmillan Publishers Limited.
homologues52. Altogether, these results suggest that view changed with the discovery of Asgard archaea.
FECA already carried some of the key building blocks Comparative analyses of Asgard archaea genomes
of the eukaryotic cytoskeleton. revealed the presence of the major components of
Genomic analyses have also led to the sugges- all three ESCRT complexes, ESCRT-I, ESCRT-II and
tion of an archaeal origin of the eukaryotic traffick- ESCRT-III47,52 (FIG. 5). The Asgard archaeal ESCRT com-
ing machinery128. Initial insights came from studies ponents are encoded in gene clusters, which seem to be
of the cren archaeote Sulfolobus acidocaldarius129,130 conserved in all known members52. Perhaps even more
that showed that a distant homologue of eukaryotic surprising was the discovery of an unexpectedly large
ESCRT-III sub unit proteins (that is, an SNF7-domain set of small GTPases in all Asgard archaea in addition to
protein) together with a Vps4-like ATPase were the presence of proteins that contain the longin domain
involved in cytokin esis in these archaea. Later, an and the roadblock/LC7 domain, which could represent
ESCRT-based cell division system was also identified in GTPase-interacting proteins47,52,133. This is remarkable
Thaumarchaeota131, Aigarchaeota and Bathyarchaeota132 because some of these elements are important regulators
(FIG. 5). Nonetheless, the differences in complexity and of the active eukary otic transport machineries and are
components between the archaeal and eukaryotic rarely or never found in other prokaryotic genomes. The
systems were found to be considerable; therefore, the genomes of Thorarchaeota were also found to encode
existence of components of the eukaryotic trafficking homologues of eukaryotic proteins that are involved
machinery in FECA remained unclear. However, this in vesicle budding and trafficking, such as transport
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protein particle complex proteins52, which are involved Nevertheless, many questions regarding the process
in the tethering of vesicles to target membranes134,135. of eukaryogenesis remain unresolved. Even though many
In addition, these genomes encode homologues of the ESPs have recently been traced back to FECA, the evolu-
Sec23 and Sec24 subunits of the coat protein complex II tionary gap between this archaeal-like ancestor and any
(COPII), which mediates anterograde transport from bona fide eukaryote is vast. The order of events and the
the endoplasmic reticulum to the Golgi apparatus135. evolutionary forces that led to the increase in cellular
Surprisingly, all Thorarchaeota genomes that have been complexity, the emergence of at least ~3,000 genes and
analysed to date possess neighbouring genes encod- the loss of many typical archaeal features (for example,
ing proteins with predicted β-propeller or α-solenoid archaeal type lipids; see BOX 2) continue to be obscure.
secondary structures. In eukaryotes, these domains In addition, the origin of bacterial genes in eukaryotes
are fused and are typically found in many vesicle coat and the role of HGT during the evolution of LECA from
complexes. This suggests that a protocoatomer gene FECA remain unclear.
repertoire was p resent in FECA52. Future research priorities should focus on obtain-
Altogether, comparative genomics of archaea, and in ing both genomic and functional data from the many
particular of members of the TACK and Asgard super- underexplored lineages of deep-branching eukaryotic
phyla, has furthered our understanding of the origin microorganisms and from Asgard archaea. Indeed,
and evolution of fundamental ESPs and provided cru- exploring archaeal diversity further might reveal even
cial insights into the nature of FECA. The discovery closer relatives of eukaryotes, uncovering a FECA that
of homologues of ESPs in these archaea suggests that is younger than previously thought and with even more
the genetic basis for some aspects of eukaryotic cellu- eukaryotic features. Similarly, it is possible that unknown
lar complexity emerged early on, before mitochondrial deeper-branching ‘eukaryotes’ that display intermediate
endosymbiosis. Identifying the likely origin of these forms of certain eukaryotic cellular features exist; this
genes during archaeal evolution (FIG. 5) could help would imply the existence of a simpler and older LECA.
to determine the relative timing of the emergence of Overall, exploring the genomic and cellular diversity
specific cellular systems that are found in eukaryotes, of archaea and eukaryotes will be crucial to revealing
before the origin of the eukaryotic lineage. the exact breadth and nature of the evolutionary gap
However, functional studies on these components between prokaryotes and eukaryotes. Improved taxo-
in archaea are much needed, not only for better under- nomic sampling among archaea will also be essential
standing the biology of these organisms but also for to confidently resolve the phylogenetic placement of
elucidating their potential biological roles in FECA. eukary otes in the tree of life. Additionally, it will clar-
The latter will be a challenging task because these func- ify the mechanisms and patterns underlying genome
tions are likely to have changed over ~2 billion years of evolution in archaea and how these have influenced the
evolutionary time, both in archaeal and in eukaryotic evolutionary history of ESPs along the archaeal tree of
lineages. life through gene loss and gain, and HGT.
Future reconstructions of the entire FECA gene rep- Concomitantly, the cultivation of members of the
ertoire will entail exploring sets of genes with different Asgard archaea will be crucial for elucidating the cellular
evolutionary fates. Indeed, this ancestor contained genes biology of these archaea and for functionally characteriz-
that were maintained both in extant Asgard archaea and ing ESPs in these organisms. This, in turn, will improve
eukaryotic genomes; the previously discussed ESPs are our understanding of the cellular nature of FECA and
part of this set. However, FECA also contained genes the functional shifts that occurred during eukaryogen-
that have been lost during eukaryogenesis and are now esis. However, this will certainly be challenging because
found only in archaea and genes that are present only in most of these archaea have so far been found in anoxic
extant eukaryotes and have been lost during ‘asgardo- environments that contain low levels of nutrients, sug-
genesis’. Finally, the eukaryote–Asgard common ances- gesting that these organisms have long generation times.
tor must have had a number of genes that were lost in In addition, Asgard archaea are difficult to isolate and
both lineages. Efforts have so far been focused on the cultivate because they usually represent low- abundant
investigation of genes that have been maintained in members of the microbial communities in which they
both lineages until today; in the long term, eukaryo- are found. Extending our understanding of the metabo-
genesis research will require an in-depth examination lism of the various Asgard archaea136–138 will be an
of the other subsets of genes. This will lead to a greater important research priority. The reconstruction and
understanding of the nature of this ancestor and could comparative analysis of the metabolic potential of mem-
improve our understanding of the origin of eukaryotes. bers of these groups not only will be essential to guide
strategies for cultivation but will also help us to under-
Conclusions and future perspectives stand the metabo lism of the pre-mitochondrial ancestor
The discovery of archaea 40 years ago led to long- of eukaryotes and to further formulate hypotheses about
lasting debates on their evolutionary relationships with the nature of the syntrophic interactions between the
eukary otes. Recent methodological improvements that mitochondrial endosymbiont and the host.
have enabled the genomes of uncultivated archaea to be Evidently, exciting times are ahead of us, and many
sequenced and explored have brought us much closer research avenues remain to be explored to lead to a
to understanding the origin and early evolution of more complete picture of the origin of eukaryotes and
eukaryotes. their early evolution from prokaryotic ancestors.
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