Available online at www.sciencedirect.com
ScienceDirect
Unifying view of stem–loop hairpin RNA as origin of
current and ancient parasitic and non-parasitic RNAs,
including in giant viruses
Hervé Seligmann and Didier Raoult
Putatively, stem–loop RNA hairpins explain networks of selfish
elements and RNA world remnants. Their genomic density
increases with intracellular lifestyle, especially when
comparing giant viruses and their virophages. RNA
protogenomes presumably templated for mRNAs and selfreplicating stem–loops, ancestors of modern genes and
parasitic sequences, including tRNAs and rRNAs. Primary and
secondary structure analyses suggest common ancestry for t/
rRNAs and parasitic RNAs, parsimoniously link diverse RNA
metabolites (replication origins, tRNAs, ribozymes,
riboswitches, miRNAs and rRNAs) to parasitic RNAs
(ribosomal viroids, Rickettsia repeated palindromic elements
(RPE), stem–loop hairpins in giant viruses, their virophages,
and transposable retrovirus-derived elements). Results
indicate ongoing genesis of small RNA metabolites, and
common ancestry or similar genesis for rRNA and retroviral
sequences. Assuming functional integration of modular
duplicated RNA hairpins evolutionarily unifies diverse
molecules, postulating stem–loop hairpin RNAs as origins of
genetic innovation, ancestors of rRNAs, retro- and Mimivirus
sequences, and cells.
Address
Unité de Recherche sur les Maladies Infectieuses et Tropicales
Émergentes, Faculté de Médecine, URMITE CNRS-IRD 198 UMER
6236, Université de la Méditerranée, 13385 Marseille, France
Corresponding author: Seligmann, Hervé (varanuseremius@gmail.com)
Current Opinion in Microbiology 2016, 31:1–8
This review comes from a themed issue on Special section:
megaviromes
In addition, retrotransposons [3], which infest all living
cells (including vertebrates as endogenous retroviruses
[4,5]) are parasites that like viroids consist of short palindrome-forming sequences.
Interestingly, parasitism by short palindromic sequences
occurs in genomes of obligatory intracellular bacteria (Rickettsia Palindromic Elements, RPE [6]) and represent up to
35% of their reduced genome [7]. Short secondary structure
forming palindromes occur in giant viruses and their virophages [8,9], where they probably function as transcription or RNA processing signals as known for tRNA genes in
vertebrate mitochondria [10]. Reduced tRNA genes probably evolved into the short stem–loop hairpin-forming
palindromes that function as replication origins
[11,12,13–16], in line with the hypothesis of a primary
replicational function for tRNAs [17]. Aminoacylation of
rat mitochondrial replication origin [18], and euplotid
nematode mitochondrial tRNAs reduced to simple
stem–loop hairpins [19] are in line with this dual replication–translation role of stem–loop hairpins, strengthened
by hints that presumed excised, isolated mitochondrial
tRNA sidearms [20] function in translation [21,22].
Here, we aim at showing that short stem–loop hairpinforming palindromic RNAs are at the origins of genomes
and the most common form of parasitism. This point is
explored along two venues, based on taxonomic comparisons and comparisons between secondary structure properties of molecules with various functions and life
histories.
Edited by Didier Raoult and Jonatas Abrahao
Genomic hairpin density increases with parasitism
http://dx.doi.org/10.1016/j.mib.2015.11.004
1369-5274/# 2015 Elsevier Ltd. All rights reserved.
Introduction
Viroids, the smallest known parasites, are one of the most
striking biological phenomena. They consist of secondary
structure forming RNA palindromes of 300–500 nucleotides, some producing epidemic plant infections [1]. The
smallest known viroid has also striking protein coding
properties [2].
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Our hypothesis assumes that short stem–loop hairpins have
high abilities at integrating genomes and at being replicated/transcribed. This predicts that palindromes with hairpin-forming capacities associate with endocellularity/
parasitism. Our sample considers that virophages and giant
viruses have parasitism levels ‘3’ and ‘2’, respectively
(parasite of virus, also parasitic). Typical intracellulars, as
the only known intracellular archaea Nanoarchaeum, and
Rickettsia conorii (alphaproteobacteria), get level 1. Mitochondria and Wolbachia, related to Rickettsia, get levels ‘1.5’
and ‘1.25’, respectively, reflecting specialization levels to
endocellularity. Various other bacteria and archaea get
parasitism level ‘0’. Genomic palindrome density increases
with endocellularity (palindrome density highest for virophages infecting giant viruses (e.g. Sputnik, virophage of
Current Opinion in Microbiology 2016, 31:1–8
2 Special section: megaviromes
Glossary
hairpin: DNA/RNA with complementary palindromes forming stem–
loop structures.
miRNA: microRNA, small RNA (about 22 nucleotides) usually
silencing mRNA expression.
polinton: giant transposon encoding polymerases.
quasispecies: self-replicating, non-identical but related entities
forming a cloud of genotypes.
repeated palindromic elements, RPE: parasitic DNA frequent in
genomes of parasitic bacteria.
replication origin: stem–loop hairpin-forming sequence at which
replication initiates (Oh, Ol-on heavy, light strands). Some tRNA genes
form Ol-like structures.
ribozyme: catalytic RNA, including hammerhead ribozyme.
riboswitch: mRNA segment regulating translation by binding a
specific small molecule.
rRNA: RNA components of ribosomes.
tmRNA: transfer-messenger RNAs, bacterial RNAs regulating
translation: stalled ribosome rescue, mRNA degradation, tagging
unfinished polypeptides for proteolysis.
transposable retrovirus-derived elements: DNA from RNA viruses
changing genomic position.
viroid: sub-viral pathogens: short, occasionally coding, circular,
single-stranded, secondary structure forming RNA.
virophage: satellite viruses inhibiting auxiliary/host virus
reproduction.
Mimivirus [23]) second highest their hosts (e.g. Mimivirus
[24], Figure 1). Conceivably, parasite genomes tolerate
more parasite sequences than genomes under greater
constraints for functional efficiency.
result from fusion after inverse duplication [44,45].
The hierarchical modular structure of the 23S rRNA
suggests a similar genesis [46]. These examples indicate
links between ribosomal RNAs and shorter functional
RNAs [47], i.e. ribozymes (Tetrahymena’s rRNA intervening sequence is an autoexcising and autocyclizing ribozyme [48]) and the ribozyme-like tmRNAs [49], which
have versatile functions (recycling stalled ribosomes at
mRNAs lacking stop codons, tagging unfinished peptides
for proteolysis and inducing degradation of dysfunctional
mRNAs [50]). The ribosome’s functional core, the universal rRNA symmetrical pocket, a dimeric RNA assembly, also suggests that rRNAs evolved from protoribosome precursors that possessed tRNA-like stem–loop
hairpin structures [51].
Viroids (some including hammerhead ribozyme structures [52,53]) mimic ribosomal structures, integrate ribosomal RNA and enhance its (and their own)
transcription [1]. Their status as missing link between
ribozymes and rRNA is strengthened by a 16-nucleotide
consensus sequence and three sets of complementary
sequences in group I introns from nuclear and mitochondrial rRNAs and chloroplast tRNAs that occurs in viroids
and virusoids (plant satellite RNA) [54,55]. Viroids also
resemble the hepatitis delta virus RNA [56], whose
replication depends upon a ribozyme structure [57], suggesting common origins.
Protogenomes, rRNAs and parasitic sequences
Hypothetically, protogenomes from an early RNA world
[25] were self-replicating rRNA-like with multiple functions, templated for translational RNAs (tRNA and
rRNA ancestors), mRNAs [26], and created parasitic
sequences, including viruses. We consider that undefined entities exchanged RNAs at high rates by lateral
transfer [27,28] and that simple replication mechanisms
with low accuracy produced numerous mutations.
Hence, classical vertical genealogies only reflect small
fractions of this mega-organic system’s evolution
[29,30], requiring rethinking classical binary evolutionary processes [31]. This ancestral system reminds quasispecies clouds of related genotypes [32–34] with a touch
of cooperativity [35]. The quasispecies concept [36] fits
modern viruses, in particular retroviruses (HIV [37]).
Viruses presumably shaped this mega-organic system
that created de novo systems and transferred sequence
information [38]. For example, eukaryotic DNA polymerases resemble those of large DNA viruses, not bacterial polymerases [39]. The transition from the RNA
world to DNA-based cells in all three ribosomal lineages
(Archaea, Bacteria and Eukarya) assumes that cellular
DNA replication originated from DNA viruses [40].
Hairpin duplication and de novo creation of molecular
species
Presumably, tRNAs result from fusion of tRNA halves
[41,42,43]. Similarly, the 5S rRNA molecule might
Current Opinion in Microbiology 2016, 31:1–8
Structural similarities cluster RNAs
Figure 2 hierarchically clusters RNAs according to variables in Table 1 (size excluded) into two main branches,
A1 includes most small RNA metabolites, including the
5.8S rRNA and viroids. Unfortunately, analyses exclude
giant virus and virophage secondary structure predictions
because available methods remain inadequate for large
sequences. This branch’s RNAs have high proportions of
‘out’ loops (unpaired nucleotides at the end of stems)
compared to ‘inner’ loops (unpaired nucleotides in the
midst of stems). Branch A2 includes most rRNAs. Its two
sub-branches distinguish RNAs with high stem GC (all
23S rRNA domains, tmRNAs, retroviruses, and some
other small RNAs) from those with low stem GC (all
16S rRNA domains, RPE, some small RNAs). Large 23S
rRNAs cluster with 5S rRNA.
Results reflect some RNA functional properties. High
proportions of ‘out’ loops in small RNA metabolites
indicate protein-binding ‘out’ loops, e.g. tRNA synthetase interactions with tRNA anticodon and sidearm loops
[58] and DNA polymerase gamma with OL loop [59].
High inner loop proportions in larger RNAs probably
reflect numerous degradation/splicing sites for endonucleases [60]. We repeated clustering analyses on each
RNA structural subelement, for all structural subelements of RNAs in Table 1. Results (not shown) overall
resemble Figure 2, however some subelements from
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Evolving parasitic stem–loop hairpin RNAs Seligmann and Raoult 3
Figure 1
0.01
Genomic palindrome density (ln)
0
0.5
1
1.5
2
2.5
3
R2 = 0.5745
1
2
3
7
4
0.001
8
9
10
18
19
20
21
22
23
24
25
17
5
11
6
12
13
16
15
14
26
27
28
0.0001
Endocellularity/parasitism level
Current Opinion in Microbiology
Palindromes and intracellular life history (all species/genomes as empty circles unless indicated for specific taxa). Palindrome density increases
independently with endocellularity in Archaea (Geoglobus + Pyrobaculum/Nanoarcheum,filled triangles); alphaproteobacteria (Pelagibacter/
Rickettsia; Wolbachia/mitochondrion), Gammaproteobacteria (Escherichia + Vibrio/Coxiella) and Megavirales (Mimivirus/Sputnik), but apparently
does not occur for others (actinobacteria: Mycobacterium/Mycobacterium + Tropheryma; firmicutes Staphylococcus/Listeria; Cyanobacteria
Prochlorococcus/Emiliana chloroplast, not shown). Giant viruses, filled circles 1. Yellowstone virophage; 2. Zamilon virophage; 3. Phaeocystis
virophage; 4. Sputnik virophage; 5. Mavirus virophage; 6. Organic lake virophage; 7. Megavirus; 8. Mimivirus; 9. Pandoravirus. Bacteria: 10.
Rickettsia conorii; 12. Coxiella burnetti; 13. Mycobacterium leprae; 14. Tropheryma whipplei; 15. Cimex lectularia Wolbachia; 16. Homo sapiens
mitochondrion; 17. Listeria monocytogenes; 18. Staphylococcus epidermis; 19. Pelagibacter ubique; 20. Staphylococcus aureus; 21.
Mycobacterium tuberculosis; 22. Streptococcus pneumonia; 23. Vibrio cholerae, chromosome 2; 24. Escherichia coli; 25. Yersinia pestis; 26. Vibrio
cholerae chromosome 1. Archaea, filled triangles: 11. Nanoarchaeum sp.; 27. Pyrobaculum aerophylum; 28. Geoglobus ahangari.
specific RNA types, cluster with those from other RNA
types, suggesting exchanges of structural RNA subelements.
in Figure 2. Hence, roughly 25% of the clustering in
Figure 2 reflects evolution (presumed sequence homology).
From structural similarities to RNA evolution
This analysis, separately for each RNA molecule, estimates congruence between distance and alignment homology for all RNA molecules compared to one specific
RNA molecule (Pearson correlation coefficient H in
Table 1). Common ancestry (homology) explains secondary structure similarity when H is negative. Otherwise,
other factors (random, adaptive convergence, de novo
genesis) determine structural similarities. H is statistically
significantly negative (P < 0.05, one-tailed test) for 21/44
Evolutionary interpretations of Figure 2 are unavoidable.
BLAST analyses between each pair of RNA molecules in
Figure 2 yield alignments whose lengths are divided by
the total lengths of compared RNAs. This homology
estimate, a proxy of evolutionary relatedness, correlates
negatively (r = 0.50) with phenotypic distance between
secondary structures, the squared Euclidean distance
between RNA pairs used for the hierarchical clustering
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Current Opinion in Microbiology 2016, 31:1–8
4 Special section: megaviromes
Figure 2
Ancestral? De novo?
Viroids
Retrovirus+23SrRNA
S
RPE+16S rRNA+tRNA
Q
U
A
0
R
E
C1
C2
D
5
E
U
B1
B2
C
D1
D2
L
10
I
D
High stem GC<->Low stem GC
rRNA<->RPE
ΔStem/loop GC
8
21
E
A
15
Out loops<->In loops
Low loop GC<->High loops GC
ΔStem/loop GC
5
25
N
D
I
20
S
T
A
A2
in loops
rRNAs
N
25
Out loops
Small RNA
A1
C
E
Current Opinion in Microbiology
Ward clustering (y axis uses the squared Euclidean distance) of RNA (four structural properties in Table 1). Arrows connect mean differences
between stem and loop GC contents for molecules on sister branches (high difference, presumably more ancient molecules).
RNAs (10/13 rRNAs (confirms rRNA monophyly), both
tmRNAs, two miRNAs, two among four ribozymes, three
among eight RPEs, one retrovirus and one tRNA cloverleaf), not for most simpler molecules, candidates for
ancestral structural RNAs and polyphyly by recent de
novo genesis (OL, riboswitches, OL-like tRNA structures
and viroids).
Rickettsia conorii (genomic RPE copy numbers should
increase with time (r = 0.715, one tailed P = 0.023,
Figure 3)), confirming that loop GC depletion indicates
time. For all Hs statistically negatively significant at
P < 0.05, H (another indicator of RNA age) decreases
with stem–loop GC content difference (for H < 0.23,
r = 0.462, one-tailed P = 0.013). Hence loop GC decay
and H reflect age, especially for ancient RNAs.
GC content reflects RNA age
GC contents are greater in stems than loops except in four
RNAs. This indicates conservation of stem GC, but not
loop GC (Table 1). Ribosomal RNA stem GC contents
increase with optimal bacterial growth temperatures [61],
rRNA loops are pyrimidine-depleted [62]. Arguably, high
GC dipole moments favor replacement by A and T (U)
[63]. Moreover, polymerases preferentially insert As and
Ts [64]. Upon RNA de novo genesis, similar stem and loop
nucleotide contents would reflect their environmental
concentrations, stem/loop GC differences should increase
with time.
This explains the increase of differences in RPE stem–
loop GC contents with RPE genomic copy numbers in
Current Opinion in Microbiology 2016, 31:1–8
Re-examination of Figure 2 considering differences in
stem/loop GC supports that branch B1 (the most diverse
in terms of types of small RNAs) includes the most
ancient RNA molecules, independently predicted by
inclusion of the OL and tRNA cloverleaf secondary
structures. Within branch A2, branch D1 includes 23S
rRNAs and retroviridae, hence probably less ancient than
branch B1. Branch D2 (primarily consisting of RPEs and
16S rRNAs), would be relatively recent, despite including
tRNAs. Hence, bacterial parasitic RNA/DNA would be
more recent than eukaryotic retroviruses. Viroids on
branch C2 would be more recent than RPEs. It is notable
that according to this criterion, branch B2 is the most
recent branch. RNA types and diversity in branch B2
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Evolving parasitic stem–loop hairpin RNAs Seligmann and Raoult 5
Table 1
Structural polynucleotide sequences and their secondary structure properties. N-sequence length; loop-percentage of nucleotides not in
stems; E-loop-percentage of nucleotides in the external loops among all nucleotides in the loops; GC stem–stem GC contents; GC loop–
loop GC contents. H is the Pearson correlation between secondary structure similarity based on the four preceding columns, and
alignment-based BLAST similarity (one tailed P < 0.05 underlined)
Molecule
Id and position
N
Loop
E-loop
GC stem
GC loop
H
Replication
OL
tRNA-OL Ala
Asn
Tyr
RPE1
RPE2
RPE3
RPE4
RPE5
RPE6
RPE7
RPE8
Viroid1 peach
Viroid2 potato
Viroid3
NC_001665: 5153–5184
NC_001665: 5010–5078
NC_001665: 5081–5152
NC_001665: 5256–5321
NC_003103: 738440–738588
NC_003103: 1143182–1143237
NC_003103: 580172–580232
NC_003103: 319964–320066
NC_003103: 249326–249451
NC_003103: 355012–355147
NC_003103: 1207290–1207425
NC_003103: 503584–503727
M83545
AY492082: 3–358
Y14700
30
70
72
65
141
104
116
103
123
134
136
144
329
336
398
33.33
37.14
55.56
38.46
31.54
55.77
39.66
28.16
38.21
28.36
39.71
22.22
27.05
29.17
31.16
100.00
19.23
52.50
72.00
12.77
51.72
26.09
34.48
31.92
42.11
35.19
18.75
60.67
66.33
62.90
80.80
31.82
28.13
45.00
45.10
43.48
37.14
41.89
40.79
38.54
45.12
20.54
53.33
58.40
62.41
30.00
23.10
40.00
40.00
36.17
37.93
36.96
24.14
36.17
18.42
25.93
37.50
46.07
48.98
42.74
0.07
0.11
0.10
0.05
0.35
0.28
0.16
0.26
0.20
0.01
0.04
0.23
0.13
0.05
0.11
Retrovirus
Retro1
Retro2
Retro3
M14008, Avian carcinoma
NC_005947, Avian EAV-HP
NC_001618, UR2 sarcoma
2830
4302
3166
41.13
37.15
39.23
18.56
24.59
20.21
63.51
59.47
55.51
36.51
42.30
36.15
0.44
0.07
0.08
Translation
tRNA cloverleaf Ala
Asn
Tyr
miRNA1
miRNA2
miRNA3
Riboswitch1
Riboswitch2
Riboswitch3
Ribozyme1
Ribozyme2
Ribozyme3a
Ribozyme3b
tmRNA E. coli
tmRNA
NC_001665: 5010–5078
NC_001665: 5081–5152
NC_001665: 5256–5321
XM_005174677: 1035–938
NR_030650: 1–103
NR_039379: 1–103
AP012050: 401275–401190*
*
CP004870: 169080–169223*
DQ680806: 56–3
*
*
*
CP005998: 4284089–4283780
HG526588*
70
72
61
97
73
68
100
92
158
191
93
57
95
360
334
37.14
47.22
37.71
38.14
53.43
48.53
58.00
47.83
53.17
42.31
50.54
47.37
60.00
40.56
38.92
19.23
73.53
21.74
29.73
20.51
42.42
77.59
47.73
57.14
50.00
38.30
59.26
91.23
11.64
11.54
31.82
36.84
42.11
68.33
50.00
52.86
54.76
64.58
45.95
46.67
47.83
56.67
44.74
65.89
88.24
23.08
23.53
52.17
78.38
41.03
54.55
17.24
22.73
36.91
45.46
36.17
44.44
42.11
34.25
44.62
0.25
0.16
0.14
0.34
0.23
0.39
0.12
0.06
0.10
0.26
0.26
0.19
0.10
0.37
0.60
rRNA
5S rRNA
5.8S rRNA
CP005998: 2761924–2761864
*
120
155
29.17
66.45
28.57
76.70
60.94
59.09
54.69
41.24
0.42
16S rRNA
Dom 1
Dom 2
Dom 3
Dom 4
JQ951605:
JQ951605:
JQ951605:
JQ951605:
1–561
562–916
917–1396
1397–1460
482
337
480
64
40.40
40.65
39.07
36.99
34.96
27.01
32.74
14.82
31.78
32.00
31.88
27.17
40.10
37.23
41.67
42.59
0.42
0.34
0.35
0.18
23S rRNA
Dom 1
Dom 2
Dom 3
Dom 4
Dom 5
Dom 6
AF053966:
AF053966:
AF053966:
AF053966:
AF053966:
AF053966:
1–561
561–1269
1271–1645
1646–2014
2015–2624
2624–2903
562
710
375
369
610
280
49.11
38.42
40.43
50.00
43.84
40.50
28.26
28.68
36.18
20.65
29.59
29.20
76.92
62.39
63.84
70.65
65.50
62.65
34.42
39.71
41.453
35.33
37.83
43.36
0.29
0.43
0.48
0.44
0.41
0.37
remind presumed ancestral branch B1. Hence, branch B2
would cluster recent de novo-generated small RNA metabolites. Accordingly, some RPEs are relatively recent
(RPE2, as Figure 3 independently suggests), others are
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more ancient. The avian carcinoma retrovirus would be
ancient compared to the two other retroviruses in Table 1
according to both GC content and H. Analyses suggest
ongoing genesis of various structural RNAs and their
Current Opinion in Microbiology 2016, 31:1–8
6 Special section: megaviromes
Figure 3
Figure 4
20
RPE6
RPE7
RPE4
ancestral RNA hairpin
Δ stem-loop GC contents
viroids
RPE1
ancestral rRNA-like genome
RPE2
RPE5
RPE3
endogenous retroviruses
y = 0.1138x - 1.7093
2
R = 0.5116
RPE
0
Prokarya: Rickettsia
Eukarya
Virophage: Sputnik
Giant viruses
RPE8
Current Opinion in Microbiology
–20
0
100
Number of RPE genomic copies
200
Current Opinion in Microbiology
GC contents difference in RPE stems and loops for different RPE
families as a function of genomic copy numbers for these RPE families
in the Rickettsia conorii genome. Genomic copy numbers (x axis) are
assumed proportional to time since infection, high differences between
stem and loop GC contents presumably reflect sequence age.
integration into genomes and cellular biomolecular machineries.
Overall discussion and conclusions
OL or ribozyme as ancestral RNA?
Analyses confirmed links between parasitism and hairpins, and parasitic RNAs and rRNAs, suggesting common
origins for retroviruses and 23S rRNA. Cluster B1 in
Figure 2 fits best the ancestral structural RNAs. It is also
the most diverse in terms of RNA types, including the
OL, a riboswitch, a ribozyme, an rRNA, and tRNA as
cloverleaf and Ol-like structure, molecules presumably
close to ancestral RNAs. Its sister cluster B2 subdivides
into C1 (also diverse, likely recent de novo generated small
RNAs (miRNA, ribozyme, riboswitch)) and the viroids
(C2).
Branch A2 (especially D1, Figure 2) clusters retroviruses
with 23S rRNAs. The 16S rRNA relates structurally with
bacterial repeated elements (RPEs). Putatively, the latter
in bacteria would play a role corresponding to that of
retroviruses in eukaryotes.
Results expand the network between viruses, transposons
and other selfish elements, to rRNAs, tRNAs and other
non-parasitic RNA metabolites. Structural similarities
with rRNAs may reflect common ancestry, indicating that
subelements from different origins generated rRNAs by
integration. An ancestral RNA stem–loop hairpin integrated genomes and assumed various roles as a singleton
Current Opinion in Microbiology 2016, 31:1–8
Schematic representation of hairpins in evolution. Hairpin-forming
palindromes, likely primordial functional RNAs, occur in all life forms,
and are over-represented in intracellular parasites, especially giant
viruses and their virophages.
(replication origin), doubleton (tRNAs) or more complex
structures (ribozymes and rRNAs). This process also
produced parasitic elements, from the short RPEs, viroids, to retroviruses, and in particular giant viruses and
virophages (Figure 4). Furthermore, the immunity mechanism by genomic retrovirus integration suggests ongoing
genomic integration of exogenous RNAs [65,66]. The
cluster including the most probable ancestral RNA molecules is also the most diverse in terms of types of RNAs.
Additionally, RNA molecules from most types apparently
recently evolved de novo independently from the major
RNA evolutionary axis (OL–tRNA–rRNA–viruses).
Analyses strengthen previous hypotheses that the first
functional RNAs were short stem–loop hairpins [67] (hairpins still play multiple roles [68]) and are a major source
for gene creation, at life’s origins and in current evolution.
They are congruent with the ribosomal protogenome
hypothesis [26] and the view that viral RNA hairpins
produced the translational machinery [69], and complement the similar-minded study based on protein 3D
structure on polyphyletic, cellular origin of viruses [70].
Competing interests
The authors declare no competing interests.
Author’s contributions
Both authors contributed equally to the manuscript.
Appendix A. Supplementary data
Supplementary material related to this article can be
found, in the online version, at http://dx.doi.org/10.
1016/j.mib.2015.11.004.
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Evolving parasitic stem–loop hairpin RNAs Seligmann and Raoult 7
Acknowledgements
For HS, this work has been carried out thanks to the support of the
A*MIDEX project (no. ANR-11-IDEX-0001-02) funded by the «
Investissements d’Avenir » French Government program, managed by the
French National Research Agency (ANR).
References and recommended reading
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have been highlighted as:
of special interest
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