Clone (cell biology)

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Clonal expansion and monoclonal versus polyclonal proliferation Clonal expansion and monoclonal versus polyclonal proliferation.PNG
Clonal expansion and monoclonal versus polyclonal proliferation

A clone is a group of identical cells that share a common ancestry, meaning they are derived from the same cell. [1]

Contents

Clonality implies the state of a cell or a substance being derived from one source or the other. Thus there are terms like polyclonal—derived from many clones; oligoclonal [2] —derived from a few clones; and monoclonal—derived from one clone. These terms are most commonly used in context of antibodies or immunocytes.

Contexts

This concept of clone assumes importance as all the cells that form a clone share common ancestry, which has a very significant consequence: shared genotype.

  1. One of the most prominent usage is in describing a clone of B cells. The B cells in the body have two important phenotypes (functional forms)—the antibody secreting, terminally differentiated (that is, they cannot divide further) plasma cells, and the memory and the naive cells—both of which retain their proliferative potential.
  2. Another important area where one can talk of "clones" of cells is neoplasms. [3] Many of the tumors derive from one (sufficiently) mutated cell, so they are technically a single clone of cells. However, during course of cell division, one of the cells can get mutated further and acquire new characteristics to diverge as a new clone. However, this view of cancer onset has been challenged in recent years and many tumors have been argued to have polyclonal origin, [4] i.e. derived from two or more cells or clones, including malignant mesothelioma. [5]
  3. All the granulosa cells in a Graafian follicle are in fact clones.
  4. Paroxysmal nocturnal hemoglobinuria is a disorder of bone marrow cells resulting in shortened life of red blood cells, which is also a result of clonal expansion, i.e., all the altered cells are originally derived from a single cell, which also somewhat compromises the functioning of other "normal" bone marrow cells. [6]

Basis of clonal proliferation

Most other cells cannot divide indefinitely as after a few cycles of cell division the cells stop expressing an enzyme telomerase. The genetic material, in the form of deoxyribonucleic acid (DNA), continues to shorten with each cell division, and cells eventually stop dividing when they sense that their DNA is critically shortened. However, this enzyme in "youthful" cells replaces these lost bits (nucleotides) of DNA, thus making almost unlimited cycles of cell division possible. It is believed that the above-mentioned tissues have a constitutional elevated expression of telomerase. When ultimately many cells are produced by a single cell, clonal expansion is said to have taken place.

Concept of clonal colony

A somewhat similar concept is that of a clonal colony (also called a genet), wherein the cells (usually unicellular) also share a common ancestry, but which also requires the products of clonal expansion to reside at "one place", or in close proximity. A clonal colony would be well exemplified by a bacterial culture colony, or the bacterial films that are more likely to be found in vivo (e.g., in infected multicellular hosts). Whereas, the cells of clones dealt with here are specialized cells of a multicellular organism (usually vertebrates), and reside at quite distant places. For instance, two plasma cells belonging to the same clone could be derived from different memory cells (in turn with shared clonality) and could be residing in quite distant locations, such as the cervical (in the neck) and inguinal (in the groin) lymph nodes.

Paramecium clonal reproduction and aging

The single-cell eukaryote Paramecium tetraurelia can undergo both asexual and sexual reproduction. Asexual or clonal reproduction occurs by binary fission. Binary fission involves mitosis-like behavior of the chromosomes similar to that of cells in higher organisms. The sexual forms of reproduction are autogamy, a kind of self-fertilization, and conjugation, a kind of sexual interation between different cells. Clonal asexual reproduction can be initiated after completion of autogamy or conjugation. P. tetraurelia is able to replicate asexually for many generations but the dividing cells gradually age and after about 200 cell divisions, if the cells fail to undergo another autogamy or conjugation, they lose vitality and expire. This process is referred to as clonal aging. Experiments by Smith-Sonneborn, [7] Holmes and Holmes [8] and Gilley and Blackburn [9] showed that accumulation of DNA damage is the likely cause of clonal aging in P. tetraurelia. This aging process has similarities to the aging process in multicellular eukaryotes (See DNA damage theory of aging).

See also

Related Research Articles

<span class="mw-page-title-main">Asexual reproduction</span> Reproduction without a sexual process

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<span class="mw-page-title-main">Reproduction</span> Biological process by which new organisms are generated from one or more parent organisms

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<i>Paramecium</i> Genus of unicellular ciliates, commonly studied as a representative of the ciliate group

Paramecium is a genus of eukaryotic, unicellular ciliates, widespread in freshwater, brackish, and marine environments. Paramecia are often abundant in stagnant basins and ponds. Because some species are readily cultivated and easily induced to conjugate and divide, they have been widely used in classrooms and laboratories to study biological processes. Paramecium species are commonly studied as model organisms of the ciliate group and have been characterized as the "white rats" of the phylum Ciliophora.

<span class="mw-page-title-main">Unicellular organism</span> Organism that consists of only one cell

A unicellular organism, also known as a single-celled organism, is an organism that consists of a single cell, unlike a multicellular organism that consists of multiple cells. Organisms fall into two general categories: prokaryotic organisms and eukaryotic organisms. Most prokaryotes are unicellular and are classified into bacteria and archaea. Many eukaryotes are multicellular, but some are unicellular such as protozoa, unicellular algae, and unicellular fungi. Unicellular organisms are thought to be the oldest form of life, with early protocells possibly emerging 3.5–4.1 billion years ago.

<span class="mw-page-title-main">Multicellular organism</span> Organism that consists of more than one cell

A multicellular organism is an organism that consists of more than one cell, unlike unicellular organisms. All species of animals, land plants and most fungi are multicellular, as are many algae, whereas a few organisms are partially uni- and partially multicellular, like slime molds and social amoebae such as the genus Dictyostelium.

<span class="mw-page-title-main">Germline</span> Population of a multicellular organisms cells that pass on their genetic material to the progeny

In biology and genetics, the germline is the population of a multicellular organism's cells that develop into germ cells. In other words, they are the cells that form gametes, which can come together to form a zygote. They differentiate in the gonads from primordial germ cells into gametogonia, which develop into gametocytes, which develop into the final gametes. This process is known as gametogenesis.

<span class="mw-page-title-main">Evolution of sexual reproduction</span>

Evolution of sexual reproduction describes how sexually reproducing animals, plants, fungi and protists could have evolved from a common ancestor that was a single-celled eukaryotic species. Sexual reproduction is widespread in eukaryotes, though a few eukaryotic species have secondarily lost the ability to reproduce sexually, such as Bdelloidea, and some plants and animals routinely reproduce asexually without entirely having lost sex. The evolution of sexual reproduction contains two related yet distinct themes: its origin and its maintenance. Bacteria and Archaea (prokaryotes) have processes that can transfer DNA from one cell to another, but it is unclear if these processes are evolutionarily related to sexual reproduction in Eukaryotes. In eukaryotes, true sexual reproduction by meiosis and cell fusion is thought to have arisen in the last eukaryotic common ancestor, possibly via several processes of varying success, and then to have persisted.

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<span class="mw-page-title-main">Neoplasm</span> Tumor or other abnormal growth of tissue

A neoplasm is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass, which may be called a tumour or tumor.

Tracy Morton Sonneborn was an American biologist. His life's study was ciliated protozoa of the group Paramecium.

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<i>Paramecium caudatum</i> Species of single-celled organism

Paramecium caudatum is a species of unicellular protist in the phylum Ciliophora. They can reach 0.33 mm in length and are covered with minute hair-like organelles called cilia. The cilia are used in locomotion and feeding. The species is very common, and widespread in marine, brackish and freshwater environments.

<span class="mw-page-title-main">Protozoa</span> Single-celled eukaryotic organisms

Protozoa are a polyphyletic group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic debris. Historically, protozoans were regarded as "one-celled animals".

<span class="mw-page-title-main">Sexual reproduction</span> Biological process

Sexual reproduction is a type of reproduction that involves a complex life cycle in which a gamete with a single set of chromosomes combines with another gamete to produce a zygote that develops into an organism composed of cells with two sets of chromosomes (diploid). This is typical in animals, though the number of chromosome sets and how that number changes in sexual reproduction varies, especially among plants, fungi, and other eukaryotes.

<span class="mw-page-title-main">Ciliate</span> Taxon of protozoans with hair-like organelles called cilia

The ciliates are a group of alveolates characterized by the presence of hair-like organelles called cilia, which are identical in structure to eukaryotic flagella, but are in general shorter and present in much larger numbers, with a different undulating pattern than flagella. Cilia occur in all members of the group and are variously used in swimming, crawling, attachment, feeding, and sensation.

<i>Paramecium aurelia</i> Species of single-celled organism

Paramecium aurelia are unicellular organisms belonging to the genus Paramecium of the phylum Ciliophora. They are covered in cilia which help in movement and feeding.Paramecium can reproduce sexually, asexually, or by the process of endomixis. Paramecium aurelia demonstrate a strong "sex reaction" whereby groups of individuals will cluster together, and emerge in conjugant pairs. This pairing can last up to 12 hours, during which the micronucleus of each organism will be exchanged. In Paramecium aurelia, a cryptic species complex was discovered by observation. Since then, some have tried to decode this complex using genetic data.

<span class="mw-page-title-main">Cancer cell</span> Tumor cell

Cancer cells are cells that divide continually, forming solid tumors or flooding the blood or lymph with abnormal cells. Cell division is a normal process used by the body for growth and repair. A parent cell divides to form two daughter cells, and these daughter cells are used to build new tissue or to replace cells that have died because of aging or damage. Healthy cells stop dividing when there is no longer a need for more daughter cells, but cancer cells continue to produce copies. They are also able to spread from one part of the body to another in a process known as metastasis.

<span class="mw-page-title-main">Immortalised cell line</span> Lineage of cells that evades senescence and continues dividing

An immortalised cell line is a population of cells from a multicellular organism that would normally not proliferate indefinitely but, due to mutation, have evaded normal cellular senescence and instead can keep undergoing division. The cells can therefore be grown for prolonged periods in vitro. The mutations required for immortality can occur naturally or be intentionally induced for experimental purposes. Immortal cell lines are a very important tool for research into the biochemistry and cell biology of multicellular organisms. Immortalised cell lines have also found uses in biotechnology.

HUMARA assay is one of the most widely used methods to determine the clonal origin of a tumor. The method is based on X chromosome inactivation and it takes advantage of the different methylation status of the gene HUMARA located on the X chromosome. Considering the fact that once one X chromosome is inactivated in a cell, all other cells derived from it will have the same X chromosome inactivated, this approach becomes a tool to differentiate a monoclonal population from a polyclonal one in a female tissue. The HUMARA gene, in particular, has three important features that make it highly convenient for the purpose:

  1. The gene is located on the X chromosome and it goes through inactivation by methylation in normal embryogenesis of a female infant. Because most genes on the X chromosome undergo inactivation, this feature is important.
  2. Human androgen receptor gene alleles have varying numbers of CAG repeats. Thus, when DNA from a healthy female tissue is amplified by polymerase chain reaction (PCR) for a specific region of the gene, two separated bands can be seen on the gel.
  3. The region that is amplified by PCR also has certain base orders that make it susceptible to be digested by HpaII enzyme when it is not methylated. This detail gives the opportunity to researchers to differentiate a methylated allele from the unmethylated allele.

Autogamy or self-fertilization refers to the fusion of two gametes that come from one individual. Autogamy is predominantly observed in the form of self-pollination, a reproductive mechanism employed by many flowering plants. However, species of protists have also been observed using autogamy as a means of reproduction. Flowering plants engage in autogamy regularly, while the protists that engage in autogamy only do so in stressful environments.

References

  1. ↑ "Clone definition – Medical Dictionary definitions of popular medical terms easily defined on MedTerms". MedicineNet.com. 2013-08-28. Archived from the original on 2012-10-25. Retrieved 2008-05-04.
  2. ↑ "oligoclonal – Definition from Merriam-Webster's Medical Dictionary". Archived from the original on 2008-03-15. Retrieved 2008-05-05.
  3. ↑ Pozo-Garcia, Lucia; Diaz-Cano, Salvador J.; Taback, Bret; Hoon, Dave S.B. (January 2003). "Clonal origin and expansions in neoplasms: biologic and technical aspects must be considered together". The American Journal of Pathology. 162 (1): 353–355. doi: 10.1016/S0002-9440(10)63826-6 . PMC   1851102 . PMID   12507918.
  4. ↑ Parsons, Barbara L. (September 2008). "Many different tumor types have polyclonal tumor origin: evidence and implications". Mutation Research. 659 (3): 232–47. Bibcode:2008MRRMR.659..232P. doi:10.1016/j.mrrev.2008.05.004. PMID   18614394.
  5. ↑ Comertpay, Sabahattin; Pastorino, Sandra; Tanji, Mika; Mezzapelle, Rosanna; Strianese, Oriana; et al. (4 December 2014). "Evaluation of clonal origin of malignant mesothelioma". Journal of Translational Medicine. 12 (1): 301. doi: 10.1186/s12967-014-0301-3 . PMC   4255423 . PMID   25471750.
  6. ↑ Bunn, Franklin; Wendell, Rosse (2005). Harrison's Principles of Internal Medicine. Vol. 1 (16th ed.). The McGraw-Hill Companies, Inc. p. 616. ISBN   0-07-144746-6.
  7. ↑ Smith-Sonneborn, J. (1979). "DNA repair and longevity assurance in Paramecium tetraurelia". Science. 203 (4385): 1115–1117. Bibcode:1979Sci...203.1115S. doi:10.1126/science.424739. PMID 424739
  8. ↑ Holmes, George E.; Holmes, Norreen R. (July 1986). "Accumulation of DNA damages in aging Paramecium tetraurelia". Molecular and General Genetics. 204 (1): 108–114. doi:10.1007/bf00330196. PMID 3091993. S2CID 11992591
  9. ↑ Gilley, David; Blackburn, Elizabeth H. (1994). "Lack of telomere shortening during senescence in Paramecium" (PDF). Proceedings of the National Academy of Sciences of the United States of America. 91 (5): 1955–1958. Bibcode:1994PNAS...91.1955G. doi:10.1073/pnas.91.5.1955. PMC 43283. PMID 8127914
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