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The initiation of a signaling pathway is a response to external stimuli. This response can take many different forms, including protein synthesis, a change in the cell’s metabolism, cell growth, or even cell death. Many pathways influence the cell by initiating gene expression, and the methods utilized are quite numerous. Some pathways activate enzymes that interact with DNA transcription factors. Others modify proteins and induce them to change their location in the cell. Depending on the status of the organism, cells can respond by storing energy as glycogen or fat, or making it available in the form of glucose. A signal transduction pathway allows muscle cells to respond to immediate requirements for energy in the form of glucose. Cell growth is almost always stimulated by external signals called growth factors. Uncontrolled cell growth leads to cancer, and mutations in the genes encoding protein components of signaling pathways are often found in tumor cells. Programmed cell death, or apoptosis, is important for removing damaged or unnecessary cells. The use of cellular signaling to organize the dismantling of a cell ensures that harmful molecules from the cytoplasm are not released into the spaces between cells, as they are in uncontrolled death, necrosis. Apoptosis also ensures the efficient recycling of the components of the dead cell. Termination of the cellular signaling cascade is very important so that the response to a signal is appropriate in both timing and intensity. Degradation of signaling molecules and dephosphorylation of phosphorylated intermediates of the pathway by phosphatases are two ways to terminate signals within the cell.
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Yeasts and multicellular organisms have similar signaling mechanisms. Yeasts use cell-surface receptors and signaling cascades to communicate information on mating with other yeast cells. The signaling molecule secreted by yeasts is called mating factor.
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Bacterial signaling is called quorum sensing. Bacteria secrete signaling molecules called autoinducers that are either small, hydrophobic molecules or peptide-based signals. The hydrophobic autoinducers, such as AHL, bind transcription factors and directly affect gene expression. The peptide-based molecules bind kinases and initiate signaling cascades in the cells.
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apoptosis : programmed cell death
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autocrine signal : signal that is sent and received by the same or similar nearby cells
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autoinducer : signaling molecule secreted by bacteria to communicate with other bacteria of its kind and others
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cell-surface receptor : cell-surface protein that transmits a signal from the exterior of the cell to the interior, even though the ligand does not enter the cell
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chemical synapse : small space between axon terminals and dendrites of nerve cells where neurotransmitters function
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cyclic AMP (cAMP) : second messenger that is derived from ATP
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cyclic AMP-dependent kinase : (also, protein kinase A, or PKA) kinase that is activated by binding to cAMP
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diacylglycerol (DAG) : cleavage product of PIP2that is used for signaling within the plasma membrane
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dimer : chemical compound formed when two molecules join together
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dimerization : (of receptor proteins) interaction of two receptor proteins to form a functional complex called a dimer
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endocrine cell : cell that releases ligands involved in endocrine signaling (hormones)
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endocrine signal : long-distance signal that is delivered by ligands (hormones) traveling through an organisms circulatory system from the signaling cell to the target cell
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enzyme-linked receptor : cell-surface receptor with intracellular domains that are associated with membrane-bound enzymes
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extracellular domain : region of a cell-surface receptor that is located on the cell surface
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G-protein-linked receptor : cell-surface receptor that activates membrane-bound G-proteins to transmit a signal from the receptor to nearby membrane components
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growth factor : ligand that binds to cell-surface receptors and stimulates cell growth
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inhibitor : molecule that binds to a protein (usually an enzyme) and keeps it from functioning
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inositol phospholipid : lipid present at small concentrations in the plasma membrane that is converted into a second messenger; it has inositol (a carbohydrate) as its hydrophilic head group
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inositol triphosphate (IP3) : cleavage product of PIP2that is used for signaling within the cell
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intercellular signaling : communication between cells
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internal receptor : (also, intracellular receptor) receptor protein that is located in the cytosol of a cell and binds to ligands that pass through the plasma membrane
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intracellular mediator : (also, second messenger) small molecule that transmits signals within a cell
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intracellular signaling : communication within cells
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ion channel-linked receptor : cell-surface receptor that forms a plasma membrane channel, which opens when a ligand binds to the extracellular domain (ligand-gated channels)
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kinase : enzyme that catalyzes the transfer of a phosphate group from ATP to another molecule
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ligand : molecule produced by a signaling cell that binds with a specific receptor, delivering a signal in the process
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mating factor : signaling molecule secreted by yeast cells to communicate to nearby yeast cells that they are available to mate and communicating their mating orientation
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neurotransmitter : chemical ligand that carries a signal from one nerve cell to the next
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paracrine signal : signal between nearby cells that is delivered by ligands traveling in the liquid medium in the space between the cells
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phosphatase : enzyme that removes the phosphate group from a molecule that has been previously phosphorylated
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phosphodiesterase : enzyme that degrades cAMP, producing AMP, to terminate signaling
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quorum sensing : method of cellular communication used by bacteria that informs them of the abundance of similar (or different) bacteria in the environment
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receptor : protein in or on a target cell that bind to ligands
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second messenger : small, non-protein molecule that propagates a signal within the cell after activation of a receptor causes its release
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signal integration : interaction of signals from two or more different cell-surface receptors that merge to activate the same response in the cell
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signal transduction : propagation of the signal through the cytoplasm (and sometimes also the nucleus) of the cell
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signaling cell : cell that releases signal molecules that allow communication with another cell
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signaling pathway : (also signaling cascade) chain of events that occurs in the cytoplasm of the cell to propagate the signal from the plasma membrane to produce a response
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synaptic signal : chemical signal (neurotransmitter) that travels between nerve cells
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target cell : cell that has a receptor for a signal or ligand from a signaling cell
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Prokaryotes have a single circular chromosome composed of double-stranded DNA, whereas eukaryotes have multiple, linear chromosomes composed of chromatin surrounded by a nuclear membrane. The 46 chromosomes of human somatic cells are composed of 22 pairs of autosomes (matched pairs) and a pair of sex chromosomes, which may or may not be matched. This is the 2nor diploid state. Human gametes have 23 chromosomes or one complete set of chromosomes; a set of chromosomes is complete with either one of the sex chromosomes. This is thenor haploid state. Genes are segments of DNA that code for a specific protein. An organism’s traits are determined by the genes inherited from each parent. Duplicated chromosomes are composed of two sister chromatids. Chromosomes are compacted using a variety of mechanisms during certain stages of the cell cycle. Several classes of protein are involved in the organization and packing of the chromosomal DNA into a highly condensed structure. The condensing complex compacts chromosomes, and the resulting condensed structure is necessary for chromosomal segregation during mitosis.
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The cell cycle is an orderly sequence of events. Cells on the path to cell division proceed through a series of precisely timed and carefully regulated stages. In eukaryotes, the cell cycle consists of a long preparatory period, called interphase. Interphase is divided into G1, S, and G2phases. The mitotic phase begins with karyokinesis (mitosis), which consists of five stages: prophase, prometaphase, metaphase, anaphase, and telophase. The final stage of the mitotic phase is cytokinesis, during which the cytoplasmic components of the daughter cells are separated either by an actin ring (animal cells) or by cell plate formation (plant cells).
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Each step of the cell cycle is monitored by internal controls called checkpoints. There are three major checkpoints in the cell cycle: one near the end of G1, a second at the G2/M transition, and the third during metaphase. Positive regulator molecules allow the cell cycle to advance to the next stage. Negative regulator molecules monitor cellular conditions and can halt the cycle until specific requirements are met.
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Cancer is the result of unchecked cell division caused by a breakdown of the mechanisms that regulate the cell cycle. The loss of control begins with a change in the DNA sequence of a gene that codes for one of the regulatory molecules. Faulty instructions lead to a protein that does not function as it should. Any disruption of the monitoring system can allow other mistakes to be passed on to the daughter cells. Each successive cell division will give rise to daughter cells with even more accumulated damage. Eventually, all checkpoints become nonfunctional, and rapidly reproducing cells crowd out normal cells, resulting in a tumor or leukemia (blood cancer).
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In both prokaryotic and eukaryotic cell division, the genomic DNA is replicated and then each copy is allocated into a daughter cell. In addition, the cytoplasmic contents are divided evenly and distributed to the new cells. However, there are many differences between prokaryotic and eukaryotic cell division. Bacteria have a single, circular DNA chromosome but no nucleus. Therefore, mitosis is not necessary in bacterial cell division. Bacterial cytokinesis is directed by a ring composed of a protein called FtsZ. Ingrowth of membrane and cell wall material from the periphery of the cells results in the formation of a septum that eventually constructs the separate cell walls of the daughter cells.
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anaphase : stage of mitosis during which sister chromatids are separated from each other
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binary fission : prokaryotic cell division process
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cell cycle : ordered sequence of events that a cell passes through between one cell division and the next
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cell cycle : ordered series of events involving cell growth and cell division that produces two new daughter cells
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cell cycle checkpoint : mechanism that monitors the preparedness of a eukaryotic cell to advance through the various cell cycle stages
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cell plate : structure formed during plant cell cytokinesis by Golgi vesicles, forming a temporary structure (phragmoplast) and fusing at the metaphase plate; ultimately leads to the formation of cell walls that separate the two daughter cells
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centriole : rod-like structure constructed of microtubules at the center of each animal cell centrosome
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centromere : region at which sister chromatids are bound together; a constricted area in condensed chromosomes
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chromatid : single DNA molecule of two strands of duplicated DNA and associated proteins held together at the centromere
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cleavage furrow : constriction formed by an actin ring during cytokinesis in animal cells that leads to cytoplasmic division
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condensin : proteins that help sister chromatids coil during prophase
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cyclin : one of a group of proteins that act in conjunction with cyclin-dependent kinases to help regulate the cell cycle by phosphorylating key proteins; the concentrations of cyclins fluctuate throughout the cell cycle
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cyclin-dependent kinase : one of a group of protein kinases that helps to regulate the cell cycle when bound to cyclin; it functions to phosphorylate other proteins that are either activated or inactivated by phosphorylation
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cytokinesis : division of the cytoplasm following mitosis that forms two daughter cells.
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diploid : cell, nucleus, or organism containing two sets of chromosomes (2n)
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FtsZ : tubulin-like protein component of the prokaryotic cytoskeleton that is important in prokaryotic cytokinesis (name origin:Filamentingtemperature-sensitive mutantZ)
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G0phase : distinct from the G1phase of interphase; a cell in G0is not preparing to divide
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G1phase : (also, first gap) first phase of interphase centered on cell growth during mitosis
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G2phase : (also, second gap) third phase of interphase during which the cell undergoes final preparations for mitosis
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gamete : haploid reproductive cell or sex cell (sperm, pollen grain, or egg)
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gene : physical and functional unit of heredity, a sequence of DNA that codes for a protein.
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genome : total genetic information of a cell or organism
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haploid : cell, nucleus, or organism containing one set of chromosomes (n)
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histone : one of several similar, highly conserved, low molecular weight, basic proteins found in the chromatin of all eukaryotic cells; associates with DNA to form nucleosomes
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homologous chromosomes : chromosomes of the same morphology with genes in the same location; diploid organisms have pairs of homologous chromosomes (homologs), with each homolog derived from a different parent
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interphase : period of the cell cycle leading up to mitosis; includes G1, S, and G2phases (the interim period between two consecutive cell divisions
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karyokinesis : mitotic nuclear division
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kinetochore : protein structure associated with the centromere of each sister chromatid that attracts and binds spindle microtubules during prometaphase
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locus : position of a gene on a chromosome
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metaphase : stage of mitosis during which chromosomes are aligned at the metaphase plate
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metaphase plate : equatorial plane midway between the two poles of a cell where the chromosomes align during metaphase
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mitosis : (also, karyokinesis) period of the cell cycle during which the duplicated chromosomes are separated into identical nuclei; includes prophase, prometaphase, metaphase, anaphase, and telophase
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mitotic phase : period of the cell cycle during which duplicated chromosomes are distributed into two nuclei and cytoplasmic contents are divided; includes karyokinesis (mitosis) and cytokinesis
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mitotic spindle : apparatus composed of microtubules that orchestrates the movement of chromosomes during mitosis
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nucleosome : subunit of chromatin composed of a short length of DNA wrapped around a core of histone proteins
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oncogene : mutated version of a normal gene involved in the positive regulation of the cell cycle
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origin : (also, ORI) region of the prokaryotic chromosome where replication begins (origin of replication)
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p21 : cell cycle regulatory protein that inhibits the cell cycle; its levels are controlled by p53
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p53 : cell cycle regulatory protein that regulates cell growth and monitors DNA damage; it halts the progression of the cell cycle in cases of DNA damage and may induce apoptosis
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prometaphase : stage of mitosis during which the nuclear membrane breaks down and mitotic spindle fibers attach to kinetochores
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prophase : stage of mitosis during which chromosomes condense and the mitotic spindle begins to form
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proto-oncogene : normal gene that when mutated becomes an oncogene
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quiescent : refers to a cell that is performing normal cell functions and has not initiated preparations for cell division
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retinoblastoma protein (Rb) : regulatory molecule that exhibits negative effects on the cell cycle by interacting with a transcription factor (E2F)
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S phase : second, or synthesis, stage of interphase during which DNA replication occurs
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septum : structure formed in a bacterial cell as a precursor to the separation of the cell into two daughter cells
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telophase : stage of mitosis during which chromosomes arrive at opposite poles, decondense, and are surrounded by a new nuclear envelope
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tumor suppressor gene : segment of DNA that codes for regulator proteins that prevent the cell from undergoing uncontrolled division
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Sexual reproduction requires that diploid organisms produce haploid cells that can fuse during fertilization to form diploid offspring. As with mitosis, DNA replication occurs prior to meiosis during the S-phase of the cell cycle. Meiosis is a series of events that arrange and separate chromosomes and chromatids into daughter cells. During the interphases of meiosis, each chromosome is duplicated. In meiosis, there are two rounds of nuclear division resulting in four nuclei and usually four daughter cells, each with half the number of chromosomes as the parent cell. The first separates homologs, and the second—like mitosis—separates chromatids into individual chromosomes. During meiosis, variation in the daughter nuclei is introduced because of crossover in prophase I and random alignment of tetrads at metaphase I. The cells that are produced by meiosis are genetically unique.
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Meiosis and mitosis share similarities, but have distinct outcomes. Mitotic divisions are single nuclear divisions that produce daughter nuclei that are genetically identical and have the same number of chromosome sets as the original cell. Meiotic divisions include two nuclear divisions that produce four daughter nuclei that are genetically different and have one chromosome set instead of the two sets of chromosomes in the parent cell. The main differences between the processes occur in the first division of meiosis, in which homologous chromosomes are paired and exchange non-sister chromatid segments. The homologous chromosomes separate into different nuclei during meiosis I, causing a reduction of ploidy level in the first division. The second division of meiosis is more similar to a mitotic division, except that the daughter cells do not contain identical genomes because of crossover.
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Nearly all eukaryotes undergo sexual reproduction. The variation introduced into the reproductive cells by meiosis appears to be one of the advantages of sexual reproduction that has made it so successful. Meiosis and fertilization alternate in sexual life cycles. The process of meiosis produces unique reproductive cells called gametes, which have half the number of chromosomes as the parent cell. Fertilization, the fusion of haploid gametes from two individuals, restores the diploid condition. Thus, sexually reproducing organisms alternate between haploid and diploid stages. However, the ways in which reproductive cells are produced and the timing between meiosis and fertilization vary greatly. There are three main categories of life cycles: diploid-dominant, demonstrated by most animals; haploid-dominant, demonstrated by all fungi and some algae; and the alternation of generations, demonstrated by plants and some algae.
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alternation of generations : life-cycle type in which the diploid and haploid stages alternate
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