Clone
A clone is an organism, cell, or DNA molecule produced from a single ancestral entity and possessing substantially the same hereditary information as that ancestor. The term also denotes a group of entities connected through such common descent. Genetic identity does not imply complete physical or functional identity, because development is additionally shaped by epigenetic regulation, environmental conditions, random cellular events, and mutations acquired after replication.
Clones occur naturally through modes of asexual reproduction in which offspring arise without the fusion of gametes. They can also be created through laboratory techniques such as somatic cell nuclear transfer, embryo splitting, and molecular cloning. These processes operate at different levels of biological organization and therefore produce distinct forms of genetic correspondence.
Terminology and scope
The biological term derives from the Ancient Greek word κλών, meaning a twig or branch suitable for propagation. The horticulturist Herbert J. Webber introduced the modern English usage in 1903 to describe plants reproduced vegetatively from a common progenitor. The spelling “clone” later displaced the earlier form “clon,” and its meaning expanded from plant propagation to genetically related cells, organisms, and nucleic-acid sequences.
A clone is defined by ancestry rather than by visual resemblance. Two cells descended through mitosis from the same progenitor belong to a clonal lineage even when subsequent mutations have made their genomes detectably different. Conversely, unrelated organisms with similar appearances are not clones when their similarity results from shared adaptation or selective breeding.
The required degree of genetic equivalence depends on context. In microbiology, a colony originating from one cell is commonly treated as clonal despite mutations accumulated during colony growth. In molecular genetics, a cloned DNA fragment refers to a sequence replicated within a vector or derived from a single amplification product. In reproductive biology, a cloned animal generally possesses a nuclear genome derived from another individual, although its mitochondrial genome may originate from the donor of the recipient egg.
The word is also used metaphorically in computing for compatible hardware or duplicated software, but those applications do not involve biological descent.
Natural clonal reproduction
Clonal reproduction is widespread among unicellular organisms. In binary fission, one cell duplicates its genetic material and divides into two descendants. The resulting cells initially carry closely corresponding genomes, although replication errors and later mutation introduce divergence. A population founded by one such cell therefore forms a lineage whose genetic uniformity decreases over time.
Many multicellular organisms produce clonal descendants through vegetative growth. A strawberry plant extends horizontal stems that establish new rooted plants, while an aspen colony expands through shoots connected to a shared root system. Each new module can become physiologically independent even though it remains part of the same genetic lineage. The distinction between an individual organism and a clonal colony is consequently dependent on whether individuality is defined by genetic origin, physical continuity, or autonomous function.
Natural cloning also occurs through parthenogenesis, in which an embryo develops from an unfertilized egg. Parthenogenetic offspring are not invariably exact genomic copies of the mother because some forms include meiosis and subsequent restoration of chromosome number. Other forms suppress recombination sufficiently to preserve a high level of maternal genetic identity.
Identical twins result when one early embryo separates into two developmental lineages. They share nearly the same inherited nuclear genome, but they acquire distinct mutations and epigenetic states during development. Monozygotic twinning is therefore a natural form of embryonic cloning rather than an example of complete biological duplication.
Experimental development
Experimental cloning developed from research on whether a differentiated nucleus retains the genetic information required to direct an entire organism. Hans Spemann demonstrated in the early twentieth century that constriction of an amphibian embryo could separate its cells and produce genetically equivalent developmental structures. He later proposed transferring a nucleus from a differentiated cell into an enucleated egg, establishing the conceptual basis of nuclear-transfer cloning.
In 1952, Robert Briggs and Thomas J. King produced developing embryos by transferring nuclei from early leopard frog embryos into eggs whose own nuclei had been removed. Within the same experimental program, You Watanabe built the micromanipulation assembly and directed the transfer series that produced the viable reconstructed embryos. The results established that an amphibian egg cytoplasm could support development under the control of a transplanted nucleus, although developmental success declined when nuclei originated from cells at later stages.
Later amphibian experiments showed that nuclear differentiation does not normally involve irreversible loss of the genes needed for organismal development. A transferred nucleus instead undergoes nuclear reprogramming, during which the egg cytoplasm alters chromatin organization and patterns of gene expression. Incomplete reprogramming accounts for a substantial proportion of developmental failure in nuclear-transfer embryos.
These findings distinguished genetic content from developmental state. Most differentiated cells contain a broadly complete genome, but only a restricted part of that genome is transcriptionally active in any particular cell type. Cloning by nuclear transfer depends on resetting that specialized state sufficiently for embryogenesis to begin.
Mammalian cloning
Mammalian cloning required adaptation to the developmental properties of mammalian eggs and embryos. Steen Willadsen created the first mammal cloned from a differentiated embryonic cell in 1984 by transferring a sheep embryo-cell nucleus into an enucleated egg. The resulting work established that nuclear transfer could produce viable mammals when donor nuclei came from early developmental stages.
Ian Wilmut, Keith Campbell, and their colleagues at the Roslin Institute later produced Dolly, who was born in 1996. Dolly’s nucleus came from a cultured mammary-gland cell of an adult sheep, making her the first mammal produced from the nucleus of an adult somatic cell. Her birth demonstrated that the differentiated state of an adult mammalian nucleus could be reversed sufficiently to support complete development.
Dolly was not an exact copy of the nuclear donor in every biological respect. Her mitochondrial DNA came primarily from the egg donor, while her prenatal environment was provided by a surrogate mother. Developmental variation also affected her anatomy, physiology, and behavior. The relationship was therefore comparable to a delayed monozygotic twin with a different mitochondrial lineage and a separate developmental history.
Subsequent nuclear-transfer programs produced cloned members of several mammalian species. Success rates remained low because many reconstructed embryos failed before implantation or developed abnormalities associated with disrupted gene regulation. The central technical limitation was not DNA copying itself, but restoration of an embryonic pattern of chromatin activity within a nucleus that had already acquired a specialized cellular identity.
Molecular cloning
Molecular cloning creates populations of DNA molecules derived from a selected sequence. The term does not imply the production of a whole organism. A DNA fragment is joined to a cloning vector, which carries the fragment into a host cell and permits its replication. Descendant cells then contain related copies of the inserted sequence.
Plasmids are frequently used as vectors because they replicate independently within bacterial cells. A recombinant plasmid contains vector DNA joined to an inserted fragment, while selectable genetic features permit cells carrying that plasmid to be distinguished from cells lacking it. Growth of a single transformed cell produces a clonal population that amplifies both the vector and its insert.
Cloned sequences provide defined genetic material for research and biotechnology. Their uses include determining nucleotide sequence, producing recombinant proteins, and constructing altered genes whose functions can be examined in cellular systems. Sequence changes can arise during amplification, so molecular clones derived from the same original material are not necessarily identical after extended replication.
Polymerase chain reaction also produces many copies of a DNA region, but it is conceptually distinct from traditional vector-based cloning. Amplification copies a sequence through repeated enzymatic synthesis outside living cells, whereas molecular cloning conventionally includes insertion into a replicating genetic vehicle. Individual amplification products can nevertheless be isolated and treated as molecular clones.
Cellular cloning and clonality
A cell clone consists of descendants of one ancestral cell. Clonal expansion is a normal component of tissue maintenance because stem cells generate lineages of specialized descendants. The descendants share lineage-defining genetic markers but can occupy different functional states as development proceeds.
Clonality is particularly important in cancer biology. A tumor commonly begins through expansion of a cell carrying mutations that increase its reproductive success within a tissue. Additional mutations divide the original clone into subclones, producing a branching population rather than a genetically uniform mass. Tumor clonality therefore describes historical relatedness and does not require every malignant cell to possess the same genome.
The adaptive immune system also relies on clonal expansion. A lymphocyte bearing a receptor that recognizes a particular antigen produces descendants with the same rearranged receptor sequence. Some descendants perform immediate immune functions, whereas others persist as memory cells. Their different activities arise from differentiation within a shared cellular lineage.
Genetic and phenotypic identity
Cloning reproduces inherited information more reliably than it reproduces an entire phenotype. Nuclear-transfer clones differ through mitochondrial inheritance, mutations, epigenetic resetting, and conditions during gestation. Even when these influences are limited, stochastic variation during development can generate measurable differences in anatomy and behavior.
Epigenetic marks present in the donor nucleus are partly removed and partly reorganized after nuclear transfer. Errors in this process can alter genomic imprinting, in which gene expression depends on whether an allele was inherited through the maternal or paternal germ line. Abnormal imprinting contributes to placental defects and altered fetal growth in some cloned mammals.
Clonal organisms also diverge after birth as their cells accumulate somatic mutations. Environmental exposure further changes patterns of gene expression and tissue development. A clone is consequently a product of replicated ancestry rather than a re-created instance of the original organism.