Satellite DNA, also known as tandemly repeated DNA, represents a diverse class of highly repetitive elements consisting of clusters of short repeated sequences. The general category of satellite DNA is now divided into several categories according to the size of the individual repeats, though the specific classification scheme can vary among authors. Thus, one may read reference to satellites (up to hundreds of base pairs per repeat), minisatellites (10-100bp per repeat), and microsatellites (only a few bp per repeat).
The term “satellite” in the genetic sense was first coined by the Russian cytologist Sergius Navashin in 1912, initially in Russian (“sputnik”) and Latin (satelle), and only later translated to “satellite” (Battaglia 1999). This original usage referred to the morphology of a chromosome possessing a secondary constriction at a certain point along its length. The more familiar usage of “satellite” relates to a small band of DNA with a density different (usually lower, because of a high AT-content) from the bulk of the genomic DNA, and which becomes separated from the main band following CsCl centrifugation (Kit 1961; Sueoka 1961). Satellite DNA was discovered in the early 1960s as an artifact of genetic studies involving this technique of centrifugation.
Satellite DNAs are non-protein-coding, and these and other repetitive sequences should have been neglected according to standard renditions of the history of research on noncoding DNA. Does the scientific literature support this claim?
Before “junk DNA” (pre-1972):
A concept that is repugnant to us is that about half of the DNA of higher organisms is trivial or permanently inert (on an evolutionary time scale). Furthermore, at least some of the members of DNA families find expression as RNA. We therefore believe that the organization of DNA into families of related sequences will ultimately be found important to the phenotype. However, at present we can only speculate on the actual role of the repeated sequences.
Britten, R.J. and D.E. Kohne. 1968. Repeated sequences in DNA. Science 161: 529-540.
The existence of repeated sequences in higher organisms led us independently to consider models of gene regulation of the type we describe here. This model depends in part on the general presence of repeated DNA sequences. The model suggests a present-day function for these repeated DNA sequences in addition to their possible evolutionary role as the raw material for creation of novel producer gene sequences. The apparently universal occurrence of large quantities of sequence repetition in the genomes of higher organisms suggests strongly that they have an important current function.
Britten, R.J. and E.H. Davidson. 1969. Gene regulation for higher cells: a theory. Science 165: 349-357.
Although we have localized mouse satellite DNA in the centromeric heterochromatin, this localization does not establish a function for either satellite DNA or heterochromatin. It seems that this function is one which is necessary to the chromosome since the proportion of satellite DNA is maintained in established mouse cell lines even though the chromosomes have undergone other morphological change.
Pardue, M.L. and J.G. Gall. 1970. Chromosomal localization of mouse satellite DNA. Science 168: 1356-1358.
One of the potentially significant aspects of this approach is that it can discover the location of defined DNA sequences on the chromosomes and relate this to their functional distribution at interphase. Thus is seems clear, from the evidence of the enriched content of nucleoli and of centric regions of chromosomes, that these become associated in interphase. The respective functions of centromeres and satellite DNA in this phenomenon are not clear, but a mechanism which obviously coordinates the physical, and perhaps the functional, aspects of different chromosomes may rely to some extent on the chemical homology of the associated satellite DNA.
Jones, K.W. 1970. Chromosomal and nuclear location of mouse satellite DNA in individual cells. Nature 225: 912-915.
Recent reports indicate that the DNA of constitutive heterochromatin is composed to a large extent of short repeated polynucleotide sequences, termed satellite DNA. This discovery has necessitated a critical review of current ideas concerning the origin and function of this portion of the genome of higher organisms. A careful appraisal of the information that has accumulated about heterochromatin since the time of Heitz and on satellite DNA during the last decade suggests that these entities have vital structural functions: they maintain nuclear organization, protect vital regions of the genome, serve as an early pairing mechanism in meiosis, and aid in speciation.
With the assumption that a portion that comprises some 10 percent of the genomes in higher organisms cannot be without a raison d’être, an extensive review led us to conclude that a certain amount of constitutive heterochromatin is essential in multicellular organisms at two levels of organization, chromosomal and nuclear. At the chromosomal level, constitutive heterochromatin is present around vital areas within the chromosomes. Around the centromeres, for example, heterochromatin is believed to confer protection and strength to the centromeric chromatin. Around secondary constrictions, heterochromatic blocks may ensure against evolutionary change of ribosomal cistrons by decreasing the frequency of crossing-over in these cistrons in meiosis and absorbing the effects of mutagenic agents. During meiosis heterochromatin may aid in the initial alignment of chromosomes prior to synapsis and may facilitate speciation by allowing chromosomal rearrangement and providing, through the species specificity of its DNA, barriers against cross-fertilization.
At the nuclear level of organization, constitutive heterochromatin may help maintain the proper spatial relationships necessary for the efficient operation of the cell through the stages of mitosis and meiosis. In the unicellular procaryotes, the presence of a small amount of genetic information in one chromosome obviates the need for constitutive heterochromatin and a nuclear membrane. At higher levels of organization, with an increase in the size of the genome and with evolution of cellular and sexual differentiation, the need for compartmentalization and structural components in the nucleus became imminent. The portion of the genome that was concerned with synthesis of ribosomal RNA was enlarged and localized in specific chromosomes, and the centromere became part of each chromosome when the mitotic spindle was developed in evolution. Concomitant with these changes in the genome, repetitive sequences in the form of constitutive heterochromatin appeared, probably as a result of large-scale duplication. The repetitive DNA’s were kept through natural selection because of their importance in preserving these vital regions and in maintaining the structural and functional integrity of the nucleus.
The association of satellite (or highly repetitive) DNA with constitutive heterochromatin is understandable, since it stresses the importance of the structural rather than transcriptional roles of these entities. Nuclear satellite DNA’s have one property in common despite their species specificity, namely heterochromatization. In this sense the apparent species specificity of satellite DNA may be the result of natural selection for duplicated short polynucleotide segments that are nontranscriptional and can be utilized in specific structural roles.
Yunis, J.J. and W.G. Yasmineh. 1971. Heterochromatin, satellite DNA, and cell function. Science 174: 1200-1209.
After “junk DNA” (1972-1980):
It has recently become possible to measure the interspersion of repetitive and single-copy DNA sequences and to estimate the length of the interspersed sequence elements. Interspersion of repetitive and non-repetitive sequences appears to be a general, if not universal, property of higher organism DNA. Similarities in the lengths of the different classes of sequence are present in the two species for which measurements are available.
These patterns are very likely of functional significance. It is our purpose in this section to focus on the evidence which, in our judgment, leads toward understanding the functional organization of the genome. We do not intend to review the entire subject of DNA sequence organization, and, for example, we only touch on the large literature dealing with satellite DNAs.
In concluding, we return to the question of the organization of DNA sequences. Our approach to gene regulation implies that the location of repetitive sequences provides the hereditary physical basis for the patterns of gene regulation. From this viewpoint, perhaps the most direct and crucial approach to the mechanism of gene regulation in higher organisms now available is the study of DNA sequence organization. More generally, an argument can be made that whether or not this particular model of gene regulation contains some elements of reality, the placement of sequences in the genome is bound to play a basic and significant role. Among the criteria of usefulness for models of gene regulation, therefore, is the extent to which they specify the structural and functional properties of DNA sequence organization. The present state of our technology, in particular of nucleic acid reassociation technology, suggests that the tools are now in hand to unravel the patterns of DNA sequence organization and their functional meaning.
Davidson, E.H. and R.J. Britten. 1973. Organization, transcription, and regulation in the animal genome. Quarterly Review of Biology 48: 565-613.
The DNA of eukaryotic organisms contains serially repeated sequences which vary in amount and complexity from one species to the next. Some of these sequences differ from the bulk of the DNA in G + C content, and hence appear as “satellites” when the DNA is banded in a CsCl density gradient. Several satellite DNAs, such as those of the mouse, the fly, Rhynchosciara and several species of Drosophila have been shown by in situ RNA-DNA hybridization to be located in the centromeric hetero-chromatin. However, very little is known about the function of satellite DNAs. There is no evidence that they code for proteins, and it is unlikely that they are even transcribed within the cell.
Because of their simple sequences the satellites of D. virilis obviously have no coding function for ordinary proteins. This conclusion is in keeping with the fact, known since the 1920’s, that the heterochromatin of Drosophila contains only a very few genes. Also because of their simple structure, and especially because they are not located in the genetic part of the chromosome, the satellites are poor candidates for regulatory genes. It is difficult to postulate any generalized function for the satellites, necessary for all cells of the organism, since the amount of satellite DNA is reduced so drastically in the polytene tissue. Similarly, there is evidence from D. melanogaster that large segments of the heterochromatin can be deleted without adverse effects either on viability or on the normal mitotic behavior of the chromosomes. Indeed the major known effect of deletion of heterochromatin, as in the sc4L scaR chromosome, is disturbance of meiotic disjunction. If the satellite DNAs have any function, it would seem to lie in the rather ill-defined category of “chromosome mechanics”, possibly including chromosome folding, meiotic pairing, or disjunction. One could even speculate that the major role is an evolutionary one, permitting only chromosomes of closely related populations to pair in meiosis, or to be involved in interchromosome exchange of the sort seen regularly in “Robertsonian fusions”.
Gall, J.G. and D.D. Atherton. 1974. Satellite DNA sequences in Drosophila virilis. Journal of Molecular Biology 85: 633-664.
An increasing proportion of the mysteriously abundant DNA of higher organisms is becoming easier to comprehend, in general terms at least. Variations in nuclear DNA content among organisms are being correlated with specific types of non-genic DNA. Several levels of apparent “bureaucracy” in the genome are becoming defined: (1) unique sequences including structural genes and other specific sequences occurring in one or two copes per genome, (2) repeated genes in a few special instances requiring high output of gene products, (3) moderately repetitive DNA sequences that are interspersed in several patterns with DNA of levels (1) and (2) and that may be involved in regulation of gene expression, and (4) highly repetitive and satellite DNA sequences, which are variable in quantity, located in massive tandem arrays, and are organized into condensed forms of chromatin. The present report has dealt with the fourth level of the hierarchy and has described its involvement in the determination of the macrostructure of chromosomes and the genome as a whole. This fourth level appears to exert the most global form of control through playing roles in adaptation to the environment and in the evolution of new species. The term “chromosome-engineering DNA” seems to express appropriately the mode of action of highly reiterated, simple sequence DNA.
Hatch, F.T., A.J. Bodner, J.A. Mazrimas, and D.H. Moore. 1976. Satellite DNA and cytogenetic evolution: DNA quantity, satellite DNA and karyotypic variations in kangaroo rates (Genus Dipodomys). Chromosoma 58: 155-168.
Proposed functions for satellite DNA were evaluated and formally set forth by Walker (1971) and have since been expanded by Mazrimas and Hatch (1972), Lagowski et al. (1973), Lee (1975), Bostock (1971), Walker (1972), and Comings (1972). In a masterful summary and evaluation of current ideas relating repeated DNA to the organization of the eukaryote chromosome (Cold Spring Harbour Symposia on Quantitative Biology 1973) Swift stated that the function of simple sequence DNAs not only appeared to have most investigators mystified, but that the present theories concerning their function were not accepted with much enthusiasm. He did, however, point out that “There is one major hope for making sense of the fact that many higher organisms seem to carry in every nucleus a large portion of their DNA that looks superficially to be completely worthless. This lies in the comparative approach. When do simple sequence DNAs arise in evolution? Can we find two closely related species one with and one without a major block of heterochromatin?”.
In summary, we believe that the Atractomorpha results focus attention on aspects of repeated DNA which are quite different to previously postulated functions. We argue that a large proportion of the highly repeated localised DNA as well as some of the repeated interspersed DNA acts in regularizing recombinational frequency and position. Thus if repeated DNA really does play a role in homologue recognition and chromosome pairing, it is now clear that only a minimum amount functions in this way, and this minimum amount need not be expressed as visible heterochromatin (as in A. australis).
Miklos, G.L.G. and R.N. Nankivell. 1976. Telomeric satellite DNA functions in regulating recombination. Chromosoma 56: 143-167.
Although much discussion has centred on the possible functions of satellite DNA (Edelman and Gally, 1970; Kohne, 1970; Walker, 1971a, b; Bostock, 1971; Yunis and Yasmineh, 1971; Comings, 1972; Rae, 1972; Jones, 1973; Hennig, 1973; Swift, 1973; Southern, 1974; Tartof, 1975; Hsu, 1975; Hatch et al., 1976) the major problem in evaluating function has been a lack of direct experimental manipulation of the satellite DNA content of any chromosome. Of the postulated functions, the more common ones would assign a role for satellite DNA in determining centromere strength (Walker, 1971a, b), aspects of chromosome pairing for regular segregation of homologs (Yunis and Yasmineh, 1971), involvement in the processes of speciation (Hatch et al., 1976), and alterations in the recombination system (Miklos and Nankivell, 1976).
The most important aspect of satellite DNA remains the nature of its functions. Although a large body of data has been gathered concerning its structure, distribution and properties in several different organisms, most of these results have in fact neither supported nor disproved any one of the particular hypotheses of function (see Comings, 1972; Swift, 1973; Hsu, 1975; Miklos and Nankivell, 1976; for evaluations of functions). The most popular hypothesis on satellite DNA function has been, and still is, that satellite DNA is involved in some aspect of chromosome mechanics such as chromosome pairing.
Yamamoto, M. and G.L.G. Miklos. 1978. Genetic studies on heterochromatin in Drosophila melanogaster and their implications for the functions of satellite DNA. Chromosoma 66: 71-98.
Satellites constitute from 1% to 65% of the total DNA of numerous organisms, including that of animals, plants, and prokaryotes. Their existence has been known for about 15 years, but, although it is thought that they must be biologically important, with few exceptions … their functions are still largely in the realm of speculation. This remains true despite their ubiquity and, except for polytenized tissues, their constancy as a fraction of the total DNA in all tissues of the particular animal or plant species in which they are observed.
The molecular diversity of this group of DNA’s, all taken together and classified as “satellites,” may be reflected in each satellite (or possibly groups of satellites) having a distinct function. This belief is based in part on the fact that there are many exceptions to nearly every generalization that has been made about satellite DNA’s.
Skinner, D.M. 1977. Satellite DNA’s. BioScience 27: 790-796.
The idea that the coordinate regulatory system of animal genomes is encoded in networks of repetitive sequence relationships is now a decade old. We and others have developed the concept that genes could be regulated by specific interactions occurring at repetitive sequences in the DNA genome. The premises have been (i) that the differentiated properties of animal cells derive from diverse and specific cytoplasmic messenger RNA (mRNA) sequence sets and (ii) that the cell-specific populations of mRNA’s result from cell-specific patterns of structural gene transcription.
Davidson, E.H. and R.J. Britten. 1979. Regulation of gene expression: possible role of repetitive sequences. Science 204: 1052-1059.
Evolutionary conservation of W [sex chromosomal] satellite DNA strongly suggests that functional constraints may have limited sequence divergence.
Singh, L., I.F. Purdom, and K.W. Jones. 1980. Sex chromosome associated satellite DNA: evolution and conservation. Chromosoma 79: 137-157.
Since the discovery that satellite DNA is located in heterochromatin, its possible role in mediating various heterochromatic functions has been the subject of both controversy and other reviews. Heterochromatin shows many very well defined functions in such diverse processes as chromosome pairing and segregation, position effect variegation, chromosome rearrangements, speciation, and recombination. All of these functions have been analyzed in great detail eithergenetically or cytogenetically, but in no case have the specific DNA sequences responsible for these phenomena been determined. Long tandem arrays that can change rapidly in evolution both qualitatively and quantitatively could act to disrupt normal chromosome behavior. However, the question remains whether such simple tandem arrays have an important positive contribution toward any of the functions attributed to heterochromatin.
With the application of recombinant DNA technology to such highly repeated sequences we now have the tools to characterize genetically altered states of heterochromatin with sufficient precision as to answer these questions.
Brutlag, D.L. 1980. Molecular arrangement and evolution of heterochromatic DNA. Annual Review of Genetics 14: 121-144.
After “selfish DNA”, the decade during which noncoding DNA supposedly was ignored (1980-1989):
The foregoing data support the concept that the so-called “junk” or genetically inactive DNA centered around the centromeric region has a function in controlling the separation of centromere (or its replication into two daughter centromeres) at the junction of metaphase-anaphase in mitosis.
Vig, B.K. 1982. Sequence of centromere separation: role of centromeric heterochromatin. Genetics 102: 795-806.
Satellite DNAs were first discovered over twenty years ago as species of DNA which, due to their unusual base composition, band at densities distinct from bulk DNA upon equilibrium sedimentation (Kit, 1961). Subsequently, it was shown that these DNAs are highly repetitious, that they are arranged in long tandem arrays, and that they are localized typically in pericentric or telocentric heterochromatin. Many of these DNAs, including mouse satellite DNA, have been sequenced. Despite detailed knowledge of the structure and location of satellite DNAs, their potential function(s) have only been hypothesized. These range from none (i.e., selfish DNA) to roles in many events including enhanced or reduced recombination, spindle attachment, gene amplification, chromosome pairing and/or segregation. Unfortunately, most of these hypotheses do not readily lend themselves to experimental investigation.
One major conclusion from the work described is that the association of kinetochores with centromeric regions of mouse chromosomes is not simply due to the presence of mouse satellite DNA sequences. However, mouse satellite DNA does appear to play a crucial role in the maintenance of contact between sister chromatids during metaphase.
Lica, L.M., S. Narayanswami, and B.A. Hamkalo. 1986. Mouse satellite DNA, centromere structure, and sister chromatid pairing. Journal of Cell Biology 103: 1145-1151.
Repetitive DNA evolves more rapidly than other genomic regions. Still, long regions of homology can be found between satellites from closely related species. Statistically significant homologies can even be found between satellites from species very distantly re- lated as the Drosophila and Bovine satellites or between animal and plant species. Whether such homologies have any functional significance, is not known.
The interpretation of these homologies can be addressed with respect to two different theories concerning the function of repeated DNA. The striking coincidence between the size of these repeat units and the mononucleosome DNA length suggests that these repeats have a role in determining chromatin structure. In fact, a sequence-dependent phasing of nucleosomes along repetitive DNA has been found in a mouse satellite DNA and in the African green monkey satellite. This could explain the homologies found between these repeats at the sequence level and also the striking conservation of their size. On the other hand, if this DNA is functionless as suggested by some authors, the homologies found could be a consequence of a common origin for many tandemly repeated families. They could have arisen from conserved genomic sequences by independent amplification events. For example, several families of interspersed repetitive sequences found in animal species are known to derive from different tRNA genes by independent amplification events. Thus, the conservation of size could be explained if, for example, nucleosomes have a role in determining the size of the sequence to be amplified.
No experimental approach to the study of the functional significance of these sequences is readily apparent at present. However, Arabidopsis, with its small genome and simple pattern of repeated DNA may eventually be a useful system for the study of these ubiquitous components of the higher eukaryotic genome.
Martinez-Zapater, J.M., M.A. Estelle, and C.R. Somerville. 1986. A highly repeated DNA sequence in Arabidopsis thaliana. Molecular and General Genetics 204: 417-423.
Tandemly repeated DNA families have long attracted considerable attention from genome-watchers, ever since satellite DNAs were originally isolated, over 20 years ago, as subsets of genomic DNA that were separable from the bulk of DNA by isopycnic centrifugation.
Willard, H.F. and J.S. Waye. 1987. Hierarchical order in chromosome-specific human alpha satellite DNA. Trends in Genetics 3: 192-198.
The species specificity of satellite profiles has long been interpreted as evidence for evolutionary instability of this class of DNA. In turn, this has led to the notion that either satellite DNAs have no function and are simply excess DNA, or that any function would be of a general nature involving chromosome condensation, pairing or recombination.
Lohe, A.R. and D.L. Brutlag. 1987. Identical satellite DNA sequences in sibling species of Drosophila. Journal of Molecular Biology 194: 161-170.
A highly conserved repetitive DNA sequence, (TTAGGG)n, has been isolated from a human recombinant repetitive DNA library. Quantitative hybridization to chromosomes sorted by flow cytometry indicates that comparable amounts of this sequence are present on each human chromosome. Both fluorescent in situ hybridization and BAL-31 nuclease digestion experiments reveal major clusters of this sequence at the telomeres of all human chromosomes. The evolutionary conservation of this DNA sequence, its terminal chromosomal location in a variety of higher eukaryotes (regardless of chromosome number or chromosome length), and its similarity to functional telomeres isolated from lower eukaryotes suggest that this sequence is a functional human telomere.
Moyzis, R.K., J.M. Buckingham, L.S. Cram, M. Dani, L.L. Deaven, M.D. Jones, J. Meyne, R.L. Ratliff, and J.-R. Wu. 1988. A highly conserved repetitive DNA sequence, (TTAGGG)n, present in the telomeres of human chromosomes. Proceedings of the National Academy of Sciences of the USA 85: 6622-6626.
The chromosomes of most mammalian species contain centromeric domains which comprise repetitive DNA sequences. Most of these domains contain blocks of simple sequence DNA families, the properties of which give rise to the characteristic C-band patterns present in mammalian chromosomes. More than one simple sequence DNA family can occupy the same centromeric domain. The biological role of these sequences in the function of an active centromere is unknown; however, one of the simple sequence DNAs in the mouse genome can bind microtubule spindle fibers, which may imply an active role for these particular DNA sequences. Recently, we have shown that one member of the human alphoid family of DNA sequences is physically closer to the functional kinetochore within the centromeric domain of human chromosome 9 than are members of the simple sequence DNA family termed satellite III.
Joseph, A., A.R. Mitchell, and O.J. Miller. 1989. The organization of the mouse satellite DNA at centromeres. Experimental Cell Research 183: 494-500.
“Noncoding DNA has been ignored until recently” (beginning around 1989-1990):
The prevailing view that satellite DNA is mostly ‘junk’ whose presence or absence has no bearing on the fitness of its carriers, has been widely accepted. Most of the support for this came from interspecific comparisons. By adding extra heterochromatic materials or by deleting nearby essential (ribosomal RNA) genes, previous studies only addressed the issue indirectly. We have provided the first direct test of this hypothesis by comparing the fitnesses of Drosophila with, and without, a well characterized array of satellite repeats. A fitness effect is clearly detectable. The observed effect is also inconsistent with the view that the functions of satellite DNA, if any, must be in the germ cells.
It is far fetched to think that all satellite DNAs have a useful role, but it is equally unwise to label them universally as junk in the absence of any other direct proof.
Wu, C.-I., J.R. True, and N. Johnson. 1989. Fitness reduction associated with the deletion of a satellite DNA array. Nature 341: 248-251.
The centromere is the major cis-acting genetic locus involved in chromosome segregation in mitosis and meiosis. The mammalian centromere is characterized by large amounts of tandemly repeated satellite DNA and by a number of specific centromere proteins, at least one of which has been shown to interact directly with centromeric satellite DNA sequences. Although direct functional assays of chromosome segregation are still lacking, the data are most consistent with a structural and possibly functional role for satellite DNA in the mammalian centromere.
As a necessary first step in the identification and characterization of DNA at mammalian centromeres, one approach has been to focus on the structure and organization of the DNA from the primary constriction. Although it has been recognized for over 20 years that the centromeric heterochromatin in chromosomes from virtually all complex eukaryotic organisms consists of various families of satellite DNA, they have only recently been taken seriously as candidates for something other than ‘junk’ DNA or genomic ‘flotsam and jetsam’ (Miklos 1985). Satellite DNA families in different mammalian orders (e.g. rodents and primates) appear largely unrelated in terms of their actual sequences; however, similarities in their overall chromosomal organization and in specific short sequences implicated in centromere protein recognition may offer enticing clues to the potential involvement of at least some satellite DNAs in centromere structure and/or function.
Willard, H.F. 1990. Centromeres of mammalian chromosomes. Trends in Genetics 6: 410-416.
Part of the Quotes of interest series.
Battaglia, E. 1999. The chromosome satellite (Navashin’s “sputnik” or satelles): a terminological comment. Acta Biologica Cracoviensia, Series Botanica 41: 15-18.
Kit, S. 1961. Equilibrium sedimentation in density gradients of DNA preparations from animal tissues. Journal of Molecular Biology 3: 711-716.
Sueoka, N. 1961. Variation and heterogeneity of base composition of deoxyribonucleic acids: a compilation of old and new data. Journal of Molecular Biology 3: 31-40.