Conversion of DNA Sequences: From a Transposable Element to a Tandem Repeat or to a Gene.

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Genes 2019, 10, 1014; doi:10.3390/genes10121014 www.mdpi.com/journal/genes
Review
Conversion of DNA Sequences: From a Transposable
Element to a Tandem Repeat or to a Gene
Ana Paço
1,
*, Renata Freitas
2,3,4
and Ana Vieira-da-Silva
1
1
MED-Mediterranean Institute for Agriculture, Environment and Development, University of Évora,
7002–554 Évora, Portugal; ana.vieiradsilva@gmail.com
2
IBMC-Institute for Molecular and Cell Biology, University of Porto, R. Campo Alegre 823,
4150–180 Porto, Portugal; Renata.Freitas@ibmc.up.pt
3
I3S-Institute for Innovation and Health Research, University of Porto, Rua Alfredo Allen, 208,
4200–135 Porto, Portugal
4
ICBAS-Institute of Biomedical Sciences Abel Salazar, University of Porto, 4050-313 Porto, Portugal
* Correspondence: apaco@uevora.pt; Tel.: +351-266-760-878
Received: 19 October 2019; Accepted: 29 November 2019; Published: 5 December 2019
Abstract: Eukaryotic genomes are rich in repetitive DNA sequences grouped in two classes
regarding their genomic organization: tandem repeats and dispersed repeats. In tandem repeats,
copies of a short DNA sequence are positioned one after another within the genome, while in
dispersed repeats, these copies are randomly distributed. In this review we provide evidence that
both tandem and dispersed repeats can have a similar organization, which leads us to suggest an
update to their classification based on the sequence features, concretely regarding the presence or
absence of retrotransposons/transposon specific domains. In addition, we analyze several studies
that show that a repetitive element can be remodeled into repetitive non-coding or coding
sequences, suggesting (1) an evolutionary relationship among DNA sequences, and (2) that the
evolution of the genomes involved frequent repetitive sequence reshuffling, a process that we have
designated as a “DNA remodeling mechanism”. The alternative classification of the repetitive DNA
sequences here proposed will provide a novel theoretical framework that recognizes the importance
of DNA remodeling for the evolution and plasticity of eukaryotic genomes.
Keywords: tandem repeats; dispersed sequences; origin of tandem repeats; mobilization of tandem
repeats; DNA remodeling mechanism
1. Introduction
Eukaryotic genomes contain a high diversity of repetitive DNA sequences [1,2]. The
amplification/deletion of these sequences contributed significantly to the extraordinary variation in
genome size found between taxa [3–7]). In the animal kingdom, the genome size could vary from 20
Mb to 130 Gb, which is mainly due to differences in the content of repetitive sequences [8]. The same
large variation was identified in plants. For instance, the fraction of repetitive genomic DNA is 13–
14% (125 Mb–157 Mb) in Arabidopsis thaliana but, contrastingly, is 77% (2.5 GB) in Zea mays [9].
The biological role of this repetitive DNA fraction has been a topic of great interest namely to
understand evolution and disease [10–13]. In summary, this fraction seems to be involved in DNA
packaging, the evolutionary events of the genome (through promoting DNA instability), gene
expression, and epigenetic mechanisms [14–25]. The analysis of the DNA sequences located in
chromosomal breakpoint regions strongly suggests that repetitive sequences work as a driving force
in the occurrence of chromosomal rearrangements, since these regions are extremely rich in these
sequences [26,27]. The repetitive nature, per se, of the different classes of repeats located in these
breakpoint regions favours recombinational events between homologous sequences in non-

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homologous regions, which may culminate in chromosomal restructurings [21]. Besides, an analysis
devoted to the transcriptional activity of some repetitive sequences input a role of these sequences in
control of gene expression, cellular response to stress and centromeric function, specifically by RNA
interference mechanisms [28].
Despite the increasing evidence pointing to a functional significance of the repetitive DNA
fraction, there are still limitations to characterizing their role in different biological processes due to
their high diversity, genomic abundance, complex evolution mode, and difficulty in isolation and
sequencing [29–31]. Thus, the real biological relevance of this fraction of eukaryotic genomes is yet to
be revealed.
This review presents a compilation of evidence on the organization and evolutionary
relationship between different classes of repetitive sequences, and between repetitive sequences and
genes. This evidence shows that the classification of repetitive sequences based on its genomic
organization as “in tandem” or “dispersed repeats” is not “as black and white”, which reinforces the
need for an updated classification. Further, this evidence also shows a high remodulation of the
repetitive sequences in the eukaryotic genomes, which could culminate in the origin of a new
sequence type, namely genes. This new way to face the classification and study of the repetitive
sequences will contribute to a better understanding of genomic plasticity and its contribution to
eukaryotic species evolution and adaptation to environment.
2. Tandem Repeats and Dispersed Repeats: Is Their Organization So Different?
Repetitive sequences are classified in two classes, tandem and dispersed repeats, according to
the genomic organization of their copies (Figure 1) [32,33]. In turn, each class is divided into several
subclasses or families [3–6,34–37]. With the goal to facilitate the annotation and classification of the
repetitive elements in eukaryotic genomes, an open access database for repetitive sequence families
(Dfam) was built [37,38].
Figure 1. Repetitive DNA sequences in eukaryotic genomes. This schematization collects the information of
several works [16,20,33,39–42]. Here, only the largest subclasses of tandem and dispersed repeats are
represented, not including the genic repetitive DNA sequences families, as tandem paralogues genes, ribosomal
genes (tandem organization), retropseudogenes, transfer RNA genes, and dispersed paralogues genes
(dispersed organization).
2.1. Tandem Repeats Organization
Traditionally, tandem repeats have been structurally characterized by a sequential arrangement
of repeat units, positioned one after the other in two possible repeat orientations, head-to-tail repeats
(direct repeats) or head-to-head repeats (inverted repeats) [33]. Excluding the genic repetitive DNA
sequences (e.g., ribosomal genes), three distinct subclasses are mainly recognized, namely
microsatellites, minisatellites, and satellites (satellite DNAs—satDNAs; nongenic tandem repeats)
(Figure 1).
It is generally considered that the main difference between micro, mini, and satellites relates to
the length of their array of repeat units in a chromosomal location [33,39,43]. Micro and minisatellites

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are classified as short tandem repeats, composed by shorter arrays of copies: ranging from 10 to 100
repeat units for microsatellites, and up to 100 repeat units for minisatellites [39,44]. However, it is
important to mention that there is no consensus on the definition of microsatellites and minisatellites,
since there is also no consensus in the repeat unit size, or in the minimal number of repeat units in an
array of copies differentiating micro and minisatellites. The threshold for repeat unit size varies
between six and 10 nucleotides [33,39,45].
The SatDNAs have traditionally been considered as organized into long arrays, with millions of
copies and, thus, have been named as long tandem repeats [39,46]. However, satDNAs with a
different organization have already been reported. Louzada and colleagues (2015) [47], identify a
satDNA (PMsat) with high sequence conservation in the genomes of five rodents. However, the
PMSat is not always organized into long array repeat units, even in species where it is highly
abundant, as is the case of Peromyscus maniculatus bairdii. In this species the authors found short
PMSsat arrays and even dispersed isolated monomers, which reinforces that the limitation of
techniques to isolate and analyse the repetitive fractions of genomes (as sequencing, assembly and
mapping technologies) is a determining factor for the study of repetitive sequences, as well as for its
accurate classification. Other reports have also come to prove the same, showing a dispersed genomic
organization of short arrays of satDNA repeat units [44,48].
Besides the length of arrays, the repeat units of satDNA (monomers) can also show a great
variation in size, ranking from five nucleotides, as in human satellite III [49], which is similar to a
micro or a minisatellite, but with longer arrays of repeat units, up to several hundred base pairs as in
the Microtus MSAT-2570 [50]. However, for plants and animals, the most common length is 150–180
bp and 300–360 bp, respectively, which is believed to be associated with the requirements of DNA
length wrapped around one or two nucleosomes [11,51,52].
The genomic distribution presented by micro, mini, and satDNAs is also traditionally
considered distinct in the literature. Generally, both microsatellites and minisatellites are distributed
throughout the genome (dispersed), in both euchromatic and heterochromatic regions [33,45].
Nevertheless, minisatellites are also characterized by their accumulations in (sub)telomeric regions
[43,53]. The satDNAs are mainly located in heterochromatic regions of the chromosomes, thus
satDNAs are preferentially found in and around centromeres [54–57]. However, once again,
exceptions have been reported as to what is generally assumed. Indeed, satDNA can also be located
at interstitial and terminal positions of chromosomes [26,47,48].
2.2. Dispersed Repeats Organization
Dispersed repeats are mainly represented by transposable elements (TEs). With the recent
proliferation of genomic sequencing studies, TEs have emerged as highly diverse, ubiquitous and
abundant genomic elements, constituting approximately half of the human genome and up to 95%
of DNA in plants [58–61]. The diversity of TEs reflects their evolutionary mode [62]. By the
accumulation of mutations, TEs generate new families and subfamilies, “escaping” to selection [63].
Despite this diversity, it was possible to group them into two major classes according to their modes
of transposition (mobilization in genomes): retrotransposons (RE, class I elements) and DNA
transposons (class II elements) (Figure 1) [60,61].
Traditionally, the dispersed repeats consist of sequences represented several times in the
genome, whose copies are not clustered or are organized in short clusters, presenting a wide
distribution throughout the genome [39,43,64]. However, some works show dispersed repeats with
an accumulated genomic organization [65–70], which can lead to the supposition of some tandem
organization for these sequences. As referred to previously, the genomic accumulation of tandem
repeats is common in certain genomic locations, such as the telomeric sequences (microsatellites of
(TTAGGG/CCCTAA)n) in the genomes of all mammals at telomeric and interstitial positions [71–73],
and satDNAs at centromeric regions [57]. In fact, different works have specifically explored the
organization of tandem repeats at telomeric and centromeric regions [26,66]. Nevertheless, how TE
blocks accumulated in certain regions of the genome are in fact organized is not reported in many

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studies. Only a few works have revealed that TE clusters could be interrupted by other TEs or also
by genes, where there might also be a short tandem arrangement of some TEs [67,69].
2.3. Repetitive Sequences: A New Classification Based on the Presence or Absence of
Retrotransposons/Transposon Specific Domains
In this review, we suggest an alternative to the traditional classification of DNA repetitive
sequences mainly based on the genomic organization of its copies. We suggest that the repetitive
sequences should not be divided as tandem repeats and dispersed repeats, once repeats organized in
tandem could also present a dispersed organization, and vice-versa. As referred to previously,
several tandem repeats have a dispersed organization in distinct genomes. In contraposition, some
TE copies may be positioned one after the other in tandem organization, presenting some
chromosomal regions several complete or incomplete copies of a specific TE. As such, these sequences
should be classified regarding other characteristics, namely the presence or absence of
retrotransposons/transposon specific domains in the sequence of its copies. Therefore, the repetitive
sequences could perhaps be classified as repeats presenting retrotransposons/transposon specific
domains or repeats not presenting retrotransposons/transposon specific domains.
3. Repetitive DNA Remodelling
Different studies show that a repetitive element can be remodelled into a different sequence,
repetitive or not, which proves an evolutionary relationship among DNA sequences, and suggests
that the evolution of the genome is characterized by a frequent repetitive sequence reshuffling, a
process that we have called a “DNA remodelling mechanism”. In fact, some authors show that the
tandem repeats could have their origin in TEs [74], and that satDNAs could also evolve to coding
sequences [75].
3.1. Transposable Elements in Origin and Genomic Distribution of Micro, Mini and Satellite DNAs
Sequence similarities between tandem repeats and TEs [76–78] indicate a strong evolutionary
relationship between these repetitive sequences. In addition, it is also believed that TEs are involved
in the origin of some sequence motifs that characterized some satDNAs, as the CENP-B box,
presenting this sequence motif strong similarity with the terminal inverted repeats of pogo
transposons [79]. In fact, computer simulations have suggested that satDNA monomers could be
generated from a wide variety of non-satellite sequences and propagated into an array by unequal
crossing-over [80]. These non-satellite sequences are often TEs [26,31,76,81–88]. In Table 1, different
examples known in the literature are listed where TEs or parts of TEs were converted into other
repetitive sequence or altered genes.
Table 1. Transposable elements in the origin of other repetitive sequence or altered genes.
Transposable element New sequence or new sequence variable Reference
SINE-like elements Satellite 1 of Xenopus leavis [89]
LTR retrotransposons RPCS satDNA of Ctenomys rodents [81]
SINE-like elements Hy/Pol III satDNA european salamander [82]
pDv mobile element pvB370 satDNA of Drosophyla virilis [83]
LINE-1 elements Common cetacean satDNA [76]
TART and HeT-A retrotransposons 18HT satDNA of Drosophila melanogaster [90]
Atenspm2 transposons Ensat1 of Arabidopsis thaliana [84]
Crwydryn retrotransposon E3900 satDNA of rye [91]
MITE elements D1100 satDNA of rye [91]
SGM-IS transposons SGM satDNA Drosophila guanche [92]
Ty3/gypsy-retroelement 250 elements of satDNA of wheat [93]
MITE-like elements Xstir satDNA of Xenopus leavis [94]
MITE elements HindIII satDNA of oysters [95]
Sore1 retrotransposon Sobo satDNA of potatoes [96]

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Table 1. Cont.
CR1 retrotransposons HinfI satDNA of chicken [97]
Ty3/gypsy-like ogre elements PisTR-A satDNa of pea [31]
MITE-like elements BIV160 satDNA of bivalves [77]
CR1-C retrotransposons Cen2, 3, 4, 7 and Cen11 satDNAs of chicken [98]
CRM1 and CRM4 retrotransposons CRM1TR satDNA of maize [87]
Helytrons elements CTRs satDNA of Drosophyla [88]
LINE-1 elements PROsat of Phodopus roborovskii [26]
Alu elements A-rich primates’ microsatellites [99]
SINE elements BARE-1, WIS2-1A and
PREM1 microsatellites of barley [100]
LINE-1 elements A-rich mammalian microsatellites [101]
Alu elements (GAA)n human microsatellite [102]
MITE elements GTCY(n) microsatellites of insects [86]
Alu elements pλg3 human minisatellite [103]
MaLR retrotyransposon Ms6-hm mouse minisatellites [104]
SINE B1 elements (GGCAGA)n mouse minisatellite [105]
Alu elements (CGGGAGGC)n human minisatellite [106]
Alu elements Minisatellites of human [107]
Gmr9/Gm ogre retrotransposons Gmr9-associated minisatellites of soybean [108]
LINE-1 elements TRIM5 gene with a cyclophilin A domain [109]
SINE: Short interspersed nuclear element, LTR: Long terminal repeats retrotransposons, LINE: Long
interspersed nuclear element, MITE: Miniature inverted repeat transposable elements, satDNA:
Satellite DNA.
The evidence for TE conversion into new non-coding repetitive sequences or genes are
reinforced by the fact that, in humans and mice—the first fully-sequenced genomes—it was estimated
that the repetitive DNA derived from TEs comprises from 40% to almost half of these genomes
[110,111]. These values could be quite underestimated, with substantial amounts of older sequences
not being detected due to their already highest divergence compared to the consensus sequences
used for their detection. Ahmed and Liang (2012) [107], for example, considered that the ability of
TEs to contribute to genome expansion is due, not only to retrotransposition (increasing its copy
number in the genomes), but also by generating tandem repeats.
The exact mechanisms underlying the origin/expansion of tandem repeats from TEs are not yet
completely known, but probably involved more than one mechanism. A tandem repeat sequence
arises after amplification events followed by subsequent molecular mechanisms. It is widely accepted
that the first repetitions of microsatellites may have originated by chance, and then expanded by
slipped-strand mispairing, as proposed by Levinson and Gutman (1987) [112]. However, some
studies suggested that TEs contain one or more sites predisposed to the formation of microsatellites.
The Poly(A) tract at the 3’ end of mammalian non-LTR retrotransposons (autonomous
LINEs/nonautonomous SINEs) provides a susceptible site to reverse transcription errors, which
could lead to the genesis of A-rich microsatellites [113]. The description of microsatellites located at
the 5’ end and internal regions of retroelements is also available in the literature [100].
Regarding minisatellites, several reports point to their origin from a variety of TE families and
subfamilies [103–106,108], namely from nonautonomous non-LTR retrotransposons as Alu and B1
SINE elements [105,106] or from LTR retrotransposons [103,104,108]. According to Haber and Louis
(1998) [114], the origin (initial event) of the first repetitions of some minisatellites appears to have
been mediated by replication slippage or unequal crossing-over, involving very short repeats (5–10
bp) that flank a motif which will be amplified as the repetition unit of these minisatellites (Figure 2).
The evidence that repetitive elements, such as Alu elements, commonly have short direct repeats in
their sequences, makes them very prone to the origin of minisatellites by this mechanism [106].
Subsequently, the amplification of the duplicated motifs into a minisatellite array could then occur
by additional replication slippage events, gene conversion, or by unequal crossing-over between the
longer homologous regions [114]. This mechanism seems plausible to explain the origin of

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minisatellites; however, it cannot explain the origin of the satDNA with larger repeat units, due to
the distance over which the initial event must have occurred (replication slippage or unequal
crossing-over involving flanking short repeats). Nevertheless, a very similar mechanism was
proposed to explain the origin of satDNAs, as for maize centromeric repeats, with most of their
monomers presenting more than 700 bp [87].
Figure 2. Initial event in the origin of the first minisatellites repetitions. Origin of a duplication by replication
slippage or unequal crossing-over between short flanking repeats, followed by a subsequent expansion into a
minisatellite.
Other interesting theories on the origin of satDNAs from TEs have been suggested. Wong and
Choo (2004) [74] proposed the “first steps” hypothesis for the origin of satDNA repetitions, based on
the duplication of part of a TE sequence by unequal crossing-over between homologous TE elements,
which could be in the same or in different chromosomes (Figure 3). Once a tandem repetition of full
or partial TEs is generated in a genome, the expansion of these novel repeat units can slowly occur
over time. Mutational changes, followed by successive rounds of crossing-over homogenization
(concerted evolution of tandem repeats), can justify the divergence observed between the emergent
satDNA and the original TE, presenting only conserved parts of their sequences [74]. This mechanism
is recurrently used to explain the origin of satDNAs. An example is the work of Dias et al. (2015) [88],
suggesting the emergence of a satDNA from central tandem repeats of a helitron (DINE-TR1) in
Drosophila species.
Figure 3. Initial steps for the origin of satDNA repeats from parts of a TE. The duplication of part of a TE sequence
occurs by unequal crossing-over between homologous dispersed repeats present in chromosomes A and B (chrA
and ChrB). The expansion of these novel repeat units can occur through time and result in a satDNA array of
copies.
The DNA transposons, or specifically their transposase activity, have been also referred to in the
birth of sequence duplications. Kapitonov and Jurka (1999) [84] propose that the breaks induced by
transposases during transposition (endonucleolytic tranposase activity) could favour recombination
processes in order to repair the double strand breaks. This event may originate the first repetitions of
a tandem repeat, which could afterwards be amplified in a large array of copies.
Beyond the role suggested in the origin of the tandem repeat, the TEs were also implicated in its
relocation/distribution throughout the genome [31,54]. It is logical to believe that when tandem

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repeats are included within the mobile element sequence (for example, when the tandem repeats
have its origin by duplication of part of TE sequence), maintaining the competence for mobilization
for these TEs. The transposition mechanism can easily disperse tandem repeats throughout the
genome (Figure 4A). This hypothesis is commonly accepted for short tandem repeats as micro and
[115–117], which present short arrays of copies compared to satDNAs [39]. In fact, a considerable part
of micro and minisatellites in eukaryotic genomes are embedded within mobile elements [115,117],
which points to an important role of TEs in its genomic distribution, explaining its common dispersed
chromosomal location. Moreover, TEs are present in pericentromeric regions of a wide range of
species [27,70,74], being these regions also mainly built by satDNAs, which certainly facilitate the
dispersion of these highly tandem repeats by retrotransposition.
Regarding LINE-1 retrotransposons, several reports suggest a location of these elements in
pericentromeric regions of different mammalian species chromosomes [27,66,70,118–120], pointing
to an intermingling of these retrotransposons with satDNAs [66,118]. This complex organization
pattern of repetitive sequences in the pericentromeric regions eventually favours the dispersion of
satDNAs to other genomic locations by LINE-1 retrotransposition, since these elements frequently
allow for the transduction of flanking non-LINE-1 DNA to new genomic locations (Figure 4B). This
transduction is a consequence of a LINE-1 incorrect retrotransposition process [121–123]. Sometimes
by retrotransposition, the TE sequences, along with its adjacent DNA, are copied and subsequently
integrated into another genomic locations. This results in the duplication and genomic dispersion of
the TE flanking sequences [124], as in, for example, satDNA monomers.
Figure 4. Dispersion of tandem repeats by transposition. (A) Origin of tandem repeats from a part of a
transposable element (TE) and its dispersion by transposition. The first duplications of a tandem repeat were
originated from a part of a TE. As these repeats are included in the TE sequence, could then be dispersed by
transposition. After, these repetitions may be amplified and homogenized in an array of copies. (B) Transduction
of tandem repeats flanking a retrotransposon and its consequent dispersion throughout the genome by
retrotransposition. Retrotransposon evidenced by a green block and tandem repeats evidenced by pink blocks.
During the evolutionary time, the tandem repeats that were moved to new chromosomal locations could be
amplified and homogenized, originating arrays of copies in these locations.

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Furthermore, we can further speculate that DNA transposons can also allow the transduction of
tandem repeats sequences [61], in a process similar to the one recognized in bacteria, for the
transference of genes (e.g., antibiotic resistance genes) within and between bacterial genomes
[125,126]. Sequences flanked by two “cut-and-paste” transposons can probably be mobilized in a
genome, when its transposases use Terminal Inverted Repeats (TIRs) of the two different transposons
to induce breaks for the mobilization (Figure 5A). If the TIRs of each DNA transposon are exclusively
used, only these elements will be mobilized. Interestingly, as referred to previously, some similarity
exists between the CENP-B box motifs and transposase recognition sites of DNA transposons [79],
which may also lead to the identification of the CENP-B boxes as a break site for transposition [127].
Therefore, the common presence of CENP-B box motif in different satDNA families [127–130] can be
involved in the mobilization of satDNAs copies during transposition [127]. No copies (monomers) of
a satDNA described as presenting CENP-B boxes have these sequence motifs [131]. Thus, several
monomers flanked by a DNA transposon and a CENP-box could be mobilized at the same time to
another location, and subsequently amplified by different recombinational mechanisms (Figure 5B).
This capacity of DNA transposons for the relocation of sequences flanked by them, or specifically by
their TIRs, is indeed already used in medicine for gene therapy [132].
Figure 5. Dispersion of tandem repeats by “cut-and-paste” transposons. (A) Mobilization of sequences flanked
by two “cut-and-paste” transposons. The breaks for the mobilization induced by transposases occur at the
terminal inverted repeats (TIRs) of the two transposons. Yellow boxes: tandem repeats monomers, blue boxes:
TIRs, violet boxes: transposase genes, grey boxes: remaining sequences of the chromosomes A and B. Chr:
chromosome. (B) Mobilization of sequences flanked by a “cut-and-paste” transposon and a CENP-B box. The
breaks for the mobilization occur at the TIRs of a transposon and a CENP-B box. Yellow boxes: tandem repeats
monomers, blue boxes: TIRs, violet boxes: transposase genes, Orange box: CENP-B box, grey boxes: remaining
sequences of the chromosomes.
3.2. Repetitive Sequences in the Origin of Coding Sequences
Transposable elements and satDNAs could also be involved in the evolution of genes, but most
interestingly in the origin of new genes or gene variants. The noticeable ability of the TEs to produce
genetic mutations when integrating at new genomic sites was recognized more than 50 years ago
[20,133]. Nevertheless, despite most of these insertions being either neutral or deleterious to their
host, its inclusions into new locations may also be advantageous, promoting gene evolution and the
codification of more efficient protein variants. One of the most publicized discoveries about this
subject is the resistance to HIV-1 (Human Immunodeficiency Virus) infection in owl monkeys, which
presents an altered TRIM5 gene with a cyclophilin A domain acquired by LINE-1 retrotransposition

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[109]. The binding of this cyclophilin domain to the HIV-1 viral capsid leads to a disruption of the
infection process [134]. However, these primates are permissive to other immunodeficiency virus,
such as the simian immunodeficiency virus (SIV) [109].
Recently, some works have shed light on questions about the de novo origin of protein-coding
genes (or variants) from non-coding DNA [75,135–137], such as satDNAs. It is believed that the origin
of completely novel genes from non-coding DNA is an evolutionary process comprising two big
steps. In the first step, the non-coding DNA sequences are transcribed and then acquire translatable
open reading frames [135] (Figure 6). Some works have already reported open reading frames in the
monomers of satDNAs [138,139], an important step that might have allowed these sequences to
evolve into coding sequences.
Figure 6. DNA remodelling process. Evolution of a satellite DNA sequence from a transposable element and its
subsequent conversion in a coding sequence. The reverse sense of the process was not proved yet. ??- Is up to
now unknown if occurs the opposite sense of this process for DNA sequences evolution.
4. Concluding Remarks
Pioneer studies on the eukaryotic genomic repetitive fraction has led to the classification of the
repetitive sequences into two major groups according to the organization of copies within the
genome: tandem repeats (as satDNAs) and dispersed repeats (TEs). Because of that, these sequences
have been mostly investigated separately, with the important evolutionary relationships that exist
between them not being considered. However, more precise genomic and bioinformatic analyses
have now shown that these sequences do not have such a tight genomic organization. Some satDNAs
may present dispersed isolated monomers in a genome [47] while TEs may have a kind of tandem
organization of their copies [69]. Moreover, it became evident that a repetitive element can often be
remodelled into a different sequence, a repetitive non-coding sequence or even a coding sequence.
This suggests that the repetitive DNA elements in eukaryotic genomes seem to be in frequent
remodulation, changing its organization and function. Therefore, an update in repetitive sequence
classification is now mandatory. Here, we have proposed a new classification for these sequences,
not based on the genomic organization of their copies, but on other sequence features, namely the
presence or absence of retrotransposon/transposon specific domains in their copies. Thus, we
propose two new groups for the classification of the repetitive sequence: repeats presenting
retrotransposons/transposons specific domains and repeats not presenting
retrotransposons/transposons specific domains. This new classification demonstrates more clearly
the evolutionary relationship between these sequences, promoting also more works to study together
sequences that were previously considered very distinct. Their joint study is indeed very important
for a better understanding of their function in genomes, showing that the evolutionary relationship

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between these sequences and the way that they can convert to each other is highly associated to the
evolution of the genomes themselves.
Accordingly, we believe that future combined studies regarding TEs and tandem repeats,
namely concerning chromosomal location and molecular similarity, will increase our knowledge
about the evolution of eukaryotic genomes. The combined studies of related repetitive sequences can
help us to understand the reason for some evolutionary tracks of sequences, and to understand these
tracks in such a way that this genome plasticity makes the eukaryotic species better adapted to
environmental conditions.
Author Contributions: Conceptualization, A.P., R.F. and A.V.d.S. and Y.Y.; writing—original draft preparation,
A.P., R.F. and A.V.d.S.; writing—review and editing, A.P., R.F. and A.V.d.S.
Funding: This work was financially supported by a Newfelpro Post-doctoral grant (No. 82) from Republic of
Croatia co-financed through the Marie Curie FP7-PEOPLE-2011-COFUND program.
Acknowledgments: We would like to acknowledge Raul Guizzo for carefully reviewing the manuscript.
Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the
study; in the collection, analyses, or interpretation of data and in the writing of the manuscript.
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