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F Factor
F F Factor S M Rosenberg and P J Hastings Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0454
The F (for fertility) factor is a conjugative plasmid of Escherichia coli. It was the first plasmid discovered and has been significant in the development and practice of bacterial genetics. Like other conjugative plasmids, the F factor encodes the machinery for its own conjugative transfer and for the transfer of other DNA molecules that contain transfer origins ± specific sequences that allow them to be mobilized (recruited and transferred) by the F-encoded transfer proteins, during bacterial conjugation.
plasmids, containing DNA from oriV clockwise to the far end of the transfer region. The F factor encodes genes for sexual pili, thin rodlike structures with which F-carrying (male or donor) bacteria attach to F± (female or recipient) cells for conjugative transfer. The F factor carries an operon of about 30 genes, encoding Tra proteins promoting transfer (Figure 1). Importantly for bacterial genetics, the F factor also contains four transposable genetic elements: two copies of the insertion sequence IS3, one IS2, and one transposon Tn1000 (also called gd). These elements are important in two respects. First, because they are also present in the E. coli chromosome, the transposable elements provide regions of DNA at which homologous recombination occurs between the F factor and the chromosome. The F IS3 Tn1000
Structure of the F Factor The F factor is 100 kb of duplex DNA with two replication-origin regions (Figure 1). The oriV or vegetative replication region contains two replication origins, one of which is used for bidirectional maintenance replication of the plasmid when it is not being transferred to another cell. oriT, the transfer origin, promotes a special mode of unidirectional, single(leading) strand replication used during conjugative transfer of the F factor to another cell. The copy number control of the F factor is similar to that of the chromosome such that there are one or two copies per bacterial chromosome. This feature has made the F factor useful to workers wishing to perform complementation and dominance tests with their gene in a single copy replicon in E. coli. This allows creation of a state of partial diploidy (also called `merodiploidy'). Originally, this was done by isolation of F0 plasmids: F factors that have incorporated often large segments of DNA from the bacterial chromosome by homologous recombination with the chromosome. Formation of F0 plasmids is described (below) in ``Importance of the F Factor in Bacterial Genetics'' (see Figure 2). Since the advent of recombinant DNA technology, smaller derivatives of the F factor have been constructed, including roughly 9-kb mini-F plasmids, containing just the oriV region, and the 55-kb pOX
100 kb IS3
tra operon IS2
F
oriT 50
oriV
Leading region
Figure 1 The F factor. The F factor is a 100-kb conjugative plasmid. The tra operon encodes functions required for conjugative transfer of the F factor. Transposable elements are indicated: IS3, IS2, and Tn1000, and the direction of transfer is indicated by the thin arrow. (Modified from Firth et al., 1996.)
678
F F act or
Bacterial chromosome
Recombination
F
Hfr
Recombination
F′
Figure 2 Formation of Hfr and F0 molecules by homologous recombination of the F plasmid with the bacterial chromosome. Transposable elements are represented as triangles, and single lines represent duplex DNA. The transposable elements present in the F plasmid provide regions of sequence identity with the E. coli chromosome and so allow the F plasmid to become incorporated into the chromosome via homologous recombination, to form an Hfr. Once incorporated, recombination may occur between transposable elements other than those that recombined upon integration of the F plasmid. This can produce an F0 plasmid. factor can integrate into the chromosome, forming an Hfr strain by this route (Figure 2). The F factor is therefore an episome, that is, a replicon that can exist either outside, or integrated into, the bacterial chromosome. Second, the Tn1000 insertion interrupts the finO ( fertility inhibition) gene. In other, similar conjugative plasmids, the FinO protein represses expression of the tra or transfer operon genes such that they are inducible upon mating. In the F factor, their expression is constitutive.
Interesting F Factor Products that May Affect DNA Metabolism Other genes carried by the F factor encode proteins that probably affect DNA metabolism in the recipient bacterium during conjugative transfer. The leading region of the F factor, that is, the region that is
transferred first, encodes a single-stranded DNA binding protein, Ssb, a protein (PsiB) that inhibits the SOS response by modifying RecA protein, and Flm, the F leading maintenance protein (also called ParL and Stm). The F factor also encodes the Ccd plasmid addiction system. Plasmid addiction systems consist of a stable toxin protein and a labile antidote protein. If the plasmid is lost from a cell, degradation of the antidote leads to killing of the cell by the stable toxin. The Ccd toxin binds the topoisomerase DNA gyrase, resulting in it functioning like a double-strand endonuclease. Flm is part of a different plasmid addiction system, with a different postsegregational killing mechanism. The plasmid addiction systems, plus the infectivity of the F factor between cells, species, genera, and domains, give an impression of a selfish DNA element. Although the F was once considered a narrow-host-range conjugative plasmid, the discovery of its transfer to distantly related bacteria and even to yeast has changed this classification.
Conjugative Transfer Cells carrying the F factor are called male or donor cells. They express long, rod-like pili on their surfaces and use these to attach to female cells for transfer of the F factor. Once attached, the pili retract, bringing the mating pair into close contact. The TraI endonuclease makes a single-strand nick at oriT, and, with its helicase activity, peels back the 50 end to which it remains covalently bound. The 30 end primes leading strand synthesis that displaces the 50 -ending strand. The displaced strand is transferred into the recipient cell. Whether the DNA is transferred through a pilus or via some other close contact is not yet clear. The synthesis and strand displacement end when the whole single-strand length of the circle has been displaced and the 30 growing end again reaches oriT. TraI is hypothesized to nick again, releasing the end of the displaced strand, and to assist recircularization of the ends in the recipient cell. Meanwhile, the complement of the transferred single-strand is synthesized in the recipient cell, such that a duplex circle is reestablished. The recipient thus becomes an F-carrying male, and the donor remains male. The Tra proteins can act on other bacterial plasmids with similar origins of transfer, including the ColE1 plasmids (from which pBR322, pUC, and many other cloning vectors are derived). The process of recruiting and transferring other plasmids is called mobilization. The sites on those plasmids that allow mobilization are called mob and the nick site itself (oriT, which is necessary but not sufficient for transfer) has also been called bom and nic. pBR322 lacks mob but carries bom, and cannot be mobilized by the F factor unless a third
F F act o r 679 Donor
F 3′ oriT Tral
Recipient
Donor
F
Recipient
Donor
F
Recipient
F
Figure 3 Conjugative transfer of the F plasmid. Each line represents a DNA strand; dashed lines represent newly synthesized DNA, and arrowheads 30 ends. During transfer, the F-encoded Tral endonuclease cleaves one strand of DNA at the transfer origin, oriT, and remains covalently bound to the 50 end. Leading-strand synthesis primed from the 30 end displaces the cleaved strand, which is transferred into a recipient cell. Lagging-strand synthesis and recircularization occur in the recipient, regenerating an F plasmid there. plasmid, apparently supplying mob function (ColK), is present. pUC plasmids contain neither mob nor bom sites and so cannot be mobilized.
Importance of the F Factor in Bacterial Genetics The original isolate of E. coli K12, from Stanford, carried an F plasmid. When Edward Tatum turned to E. coli for generalization of his biochemical genetic studies with Beadle (which led to the ``one gene, one enzyme'' hypothesis) in the fungus Neurospora, he made auxotrophic mutants of E. coli K12. To bring about mutagenesis, he used large doses of radiation, which caused loss of the F factor in some of the derivative strains. Joshua Lederberg's interest in testing whether mating could occur between different E. coli auxotrophic mutant strains, to give prototrophic recombinants (the selection of which he invented), led to his joining Tatum and using K12derived strains (Lederberg and Tatum, 1946b) Because some of the strains had lost their F factor and others had not, Lederberg discovered mating and recombination in bacteria. In strains that retained the F factor, the F factor could integrate into the bacterial chromosome. The integrated F factor can transfer segments of chromosomal DNA contiguous with its integration site during conjugation, and these can be recombined into the recipient chromosome, resulting in the prototrophic recombinant bacteria reported by Lederberg and Tatum in 1946 (Lederberg and Tatum, 1946b) (Hfr). The results encouraged the idea that bacteria, like other organisms, had genes, and led to much of our current understanding of DNA recombination. Strains with the F factor integrated are called Hfr (high-frequency recombination) strains (Hfr). The integrated F factor can be excised from the chromosome using homologous recombination with the same insertion sequences used upon its integration to
regenerate an F plasmid (a wild-type F plasmid with no bacterial DNA incorporated into it). If different insertion sequences from the bacterial chromosomal DNA are used for direct repeat recombination excising the F factor, then the F factor brings with it chromosomal DNA, forming an F0 factor (Figure 2). The discoveries by William Hayes, Elie Wollman, and FrancËois Jacob that the F factor is a plasmid, and the subsequent discoveries of other bacterial plasmids, made possible the development of plasmid vectors for molecular cloning (Hayes, 1952; Wollman et al., 1956; Jacob and Wollman, 1958). Fs are important replicons used in single-copy gene-complementation experiments and in tests of dominance. As discussed in Hfr, the use of Hfrs for studies of bacterial recombination led tothecharacterizationofmechanismsandproteinsused in homologous genetic recombination in E. coli, and, because the DNA transferred in Hfr crosses is linear, the enzymes used in double-strand break-repair were illuminated in these studies. Descriptions of those proteins, bacterial recombination, and double-strand break-repair are given in Rec Genes, Recombination Pathways, RecA Protein and Homology, RecBCD Enzyme, Pathway, RuvAB Enzyme, RuvC Enzyme.
Further Reading
Brock TD (1990) The Emergence of Bacterial Genetics. Plainview, NY: Cold Spring Harbor Laboratory Press. Firth N, Ippen-Ihler K and Skurray RH (1996) Structure and function of the F factor and mechanism of conjugation. In: Neidhardt FC, Curtiss III R, Ingraham JL et al. (eds) Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 2, pp. 2377±2401. Washington, DC: ASM Press. Holloway B and Low KB (1996) F-prime and R-prime factors. In: Neidhardt FC, Curtiss III R, Ingraham JL et al. (eds) Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 2, pp. 2413±2420. Washington, DC: ASM Press.
680
F1 Generation
Low KB (1996) Hfr strains of Escherichia coli K12. In: Neidhardt FC, Curtiss III R, Ingraham JL et al. (eds) Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 2, 2402±2405. Washington, DC: ASM Press.
References
Hayes W (1952) Recombination in E. coli K12: unidirectional transfer of genetic material. Nature 169: 118±119. Jacob F and Wollman EL (1958) Les eÂpisomes, eÂleÂments geÂneÂtiques ajouteÂs. Comptes Rendus de l'AcadeÂmie des Sciences 242: 303±306. Lederberg J and Tatum EL (1946a) Gene recombination in bacteria. Nature 158: 558. Lederberg J and Tatum EL (1946b) Novel genotypes in mixed cultures of biochemical mutants of bacteria. Cold Spring Harbor Symposia on Quantitative Biology 11: 113±114. Wollman EL Jacob F and Hayes W (1956) Conjugation and genetic recombination in Escherichia coli K12. Cold Spring Harbor Symposia on Quantitative Biology 21: 141±162.
weight, life span, fecundity, litter size, and resistance to disease and experimental manipulations. It is possible to generate organisms that are genetically uniform without suffering the consequences of whole genome homozygosity. This is accomplished by simply crossing two inbred strains to each other. The resulting F1 hybrid organisms express hybrid vigor in all of the fitness characteristics just listed with an overall life span that will exceed that of both inbred parents. Furthermore, as long as both of the parental inbred strains are maintained, it will be possible to produce F1 hybrids between the two, and all F1 hybrids obtained from the same cross will be genetically identical to each other over time and space. Of course, uniformity will not be preserved in the offspring that result from an ``intercross'' between two F1 hybrids (see Intercross); instead random segregation and independent assortment will lead to F2 animals that are all genotypically distinct.
See also: Conjugation, Bacterial; Conjugative Transposition; Hfr; Plasmids
See also: Hybrid Vigor; Intercross
F1 Generation
FAB Classification of Leukemia
Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1839
The F1 generation is the first generation resulting from a cross between two dissimilar parental lines. See also: Mendelian Genetics; Mendelian Inheritance
F1 Hybrid L Silver Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0442
The most obvious advantage of working with inbred strains is genetic uniformity over time and space. Researchers can be confident that the inbred animals of a particular strain used in experiments today are essentially the genetic equivalent of animals from the same strain used 10 years ago. Thus, the existence of inbred strains serves to eliminate the contribution of genetic variability to the interpretation of experimental results. However, there is a serious disadvantage to working with inbred animals in that a completely inbred genome is an abnormal condition with detrimental phenotypic consequences. The lack of genomic heterozygosity is responsible for a generalized decrease in a number of fitness characteristics including body
B Bain Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1569
From 1976 onward, a French±American±British (FAB) cooperative group of hematologists formulated a series of classifications of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), the myelodysplastic syndromes, chronic lymphoid leukemias, and the leukemic phase of non-Hodgkin's lymphoma. These classifications were initially based only on cytology and cytochemistry, but immunophenotypic analysis was later incorporated. Subsequently it became apparent that several FAB categories of leukemia identified specific cytogenetic/molecular genetic entities, e.g., M3 AML (hypergranular promyelocytic leukemia) and L3 ALL (Burkitt's lymphoma-related acute leukemia). Other FAB categories included more than one specific cytogenetic/molecular genetic entity, e.g., M5 AML was found to include not only various acute monocytic/monoblastic leukemias associated with t(9;11)(p21-22;q23) and other translocations with an 11q23 breakpoint, but also the completely different entity, acute monoblastic leukemia associated with t(8;16)(p11;p13). The FAB classifications were important in advancing knowledge of hematological malignancies, since they provided a framework for cytogenetic and molecular genetic
The F (for fertility) factor is a conjugative plasmid of Escherichia coli. It was the first plasmid discovered and has been significant in the development and practice of bacterial genetics. Like other conjugative plasmids, the F factor encodes the machinery for its own conjugative transfer and for the transfer of other DNA molecules that contain transfer origins ± specific sequences that allow them to be mobilized (recruited and transferred) by the F-encoded transfer proteins, during bacterial conjugation.
plasmids, containing DNA from oriV clockwise to the far end of the transfer region. The F factor encodes genes for sexual pili, thin rodlike structures with which F-carrying (male or donor) bacteria attach to F± (female or recipient) cells for conjugative transfer. The F factor carries an operon of about 30 genes, encoding Tra proteins promoting transfer (Figure 1). Importantly for bacterial genetics, the F factor also contains four transposable genetic elements: two copies of the insertion sequence IS3, one IS2, and one transposon Tn1000 (also called gd). These elements are important in two respects. First, because they are also present in the E. coli chromosome, the transposable elements provide regions of DNA at which homologous recombination occurs between the F factor and the chromosome. The F IS3 Tn1000
Structure of the F Factor The F factor is 100 kb of duplex DNA with two replication-origin regions (Figure 1). The oriV or vegetative replication region contains two replication origins, one of which is used for bidirectional maintenance replication of the plasmid when it is not being transferred to another cell. oriT, the transfer origin, promotes a special mode of unidirectional, single(leading) strand replication used during conjugative transfer of the F factor to another cell. The copy number control of the F factor is similar to that of the chromosome such that there are one or two copies per bacterial chromosome. This feature has made the F factor useful to workers wishing to perform complementation and dominance tests with their gene in a single copy replicon in E. coli. This allows creation of a state of partial diploidy (also called `merodiploidy'). Originally, this was done by isolation of F0 plasmids: F factors that have incorporated often large segments of DNA from the bacterial chromosome by homologous recombination with the chromosome. Formation of F0 plasmids is described (below) in ``Importance of the F Factor in Bacterial Genetics'' (see Figure 2). Since the advent of recombinant DNA technology, smaller derivatives of the F factor have been constructed, including roughly 9-kb mini-F plasmids, containing just the oriV region, and the 55-kb pOX
100 kb IS3
tra operon IS2
F
oriT 50
oriV
Leading region
Figure 1 The F factor. The F factor is a 100-kb conjugative plasmid. The tra operon encodes functions required for conjugative transfer of the F factor. Transposable elements are indicated: IS3, IS2, and Tn1000, and the direction of transfer is indicated by the thin arrow. (Modified from Firth et al., 1996.)
678
F F act or
Bacterial chromosome
Recombination
F
Hfr
Recombination
F′
Figure 2 Formation of Hfr and F0 molecules by homologous recombination of the F plasmid with the bacterial chromosome. Transposable elements are represented as triangles, and single lines represent duplex DNA. The transposable elements present in the F plasmid provide regions of sequence identity with the E. coli chromosome and so allow the F plasmid to become incorporated into the chromosome via homologous recombination, to form an Hfr. Once incorporated, recombination may occur between transposable elements other than those that recombined upon integration of the F plasmid. This can produce an F0 plasmid. factor can integrate into the chromosome, forming an Hfr strain by this route (Figure 2). The F factor is therefore an episome, that is, a replicon that can exist either outside, or integrated into, the bacterial chromosome. Second, the Tn1000 insertion interrupts the finO ( fertility inhibition) gene. In other, similar conjugative plasmids, the FinO protein represses expression of the tra or transfer operon genes such that they are inducible upon mating. In the F factor, their expression is constitutive.
Interesting F Factor Products that May Affect DNA Metabolism Other genes carried by the F factor encode proteins that probably affect DNA metabolism in the recipient bacterium during conjugative transfer. The leading region of the F factor, that is, the region that is
transferred first, encodes a single-stranded DNA binding protein, Ssb, a protein (PsiB) that inhibits the SOS response by modifying RecA protein, and Flm, the F leading maintenance protein (also called ParL and Stm). The F factor also encodes the Ccd plasmid addiction system. Plasmid addiction systems consist of a stable toxin protein and a labile antidote protein. If the plasmid is lost from a cell, degradation of the antidote leads to killing of the cell by the stable toxin. The Ccd toxin binds the topoisomerase DNA gyrase, resulting in it functioning like a double-strand endonuclease. Flm is part of a different plasmid addiction system, with a different postsegregational killing mechanism. The plasmid addiction systems, plus the infectivity of the F factor between cells, species, genera, and domains, give an impression of a selfish DNA element. Although the F was once considered a narrow-host-range conjugative plasmid, the discovery of its transfer to distantly related bacteria and even to yeast has changed this classification.
Conjugative Transfer Cells carrying the F factor are called male or donor cells. They express long, rod-like pili on their surfaces and use these to attach to female cells for transfer of the F factor. Once attached, the pili retract, bringing the mating pair into close contact. The TraI endonuclease makes a single-strand nick at oriT, and, with its helicase activity, peels back the 50 end to which it remains covalently bound. The 30 end primes leading strand synthesis that displaces the 50 -ending strand. The displaced strand is transferred into the recipient cell. Whether the DNA is transferred through a pilus or via some other close contact is not yet clear. The synthesis and strand displacement end when the whole single-strand length of the circle has been displaced and the 30 growing end again reaches oriT. TraI is hypothesized to nick again, releasing the end of the displaced strand, and to assist recircularization of the ends in the recipient cell. Meanwhile, the complement of the transferred single-strand is synthesized in the recipient cell, such that a duplex circle is reestablished. The recipient thus becomes an F-carrying male, and the donor remains male. The Tra proteins can act on other bacterial plasmids with similar origins of transfer, including the ColE1 plasmids (from which pBR322, pUC, and many other cloning vectors are derived). The process of recruiting and transferring other plasmids is called mobilization. The sites on those plasmids that allow mobilization are called mob and the nick site itself (oriT, which is necessary but not sufficient for transfer) has also been called bom and nic. pBR322 lacks mob but carries bom, and cannot be mobilized by the F factor unless a third
F F act o r 679 Donor
F 3′ oriT Tral
Recipient
Donor
F
Recipient
Donor
F
Recipient
F
Figure 3 Conjugative transfer of the F plasmid. Each line represents a DNA strand; dashed lines represent newly synthesized DNA, and arrowheads 30 ends. During transfer, the F-encoded Tral endonuclease cleaves one strand of DNA at the transfer origin, oriT, and remains covalently bound to the 50 end. Leading-strand synthesis primed from the 30 end displaces the cleaved strand, which is transferred into a recipient cell. Lagging-strand synthesis and recircularization occur in the recipient, regenerating an F plasmid there. plasmid, apparently supplying mob function (ColK), is present. pUC plasmids contain neither mob nor bom sites and so cannot be mobilized.
Importance of the F Factor in Bacterial Genetics The original isolate of E. coli K12, from Stanford, carried an F plasmid. When Edward Tatum turned to E. coli for generalization of his biochemical genetic studies with Beadle (which led to the ``one gene, one enzyme'' hypothesis) in the fungus Neurospora, he made auxotrophic mutants of E. coli K12. To bring about mutagenesis, he used large doses of radiation, which caused loss of the F factor in some of the derivative strains. Joshua Lederberg's interest in testing whether mating could occur between different E. coli auxotrophic mutant strains, to give prototrophic recombinants (the selection of which he invented), led to his joining Tatum and using K12derived strains (Lederberg and Tatum, 1946b) Because some of the strains had lost their F factor and others had not, Lederberg discovered mating and recombination in bacteria. In strains that retained the F factor, the F factor could integrate into the bacterial chromosome. The integrated F factor can transfer segments of chromosomal DNA contiguous with its integration site during conjugation, and these can be recombined into the recipient chromosome, resulting in the prototrophic recombinant bacteria reported by Lederberg and Tatum in 1946 (Lederberg and Tatum, 1946b) (Hfr). The results encouraged the idea that bacteria, like other organisms, had genes, and led to much of our current understanding of DNA recombination. Strains with the F factor integrated are called Hfr (high-frequency recombination) strains (Hfr). The integrated F factor can be excised from the chromosome using homologous recombination with the same insertion sequences used upon its integration to
regenerate an F plasmid (a wild-type F plasmid with no bacterial DNA incorporated into it). If different insertion sequences from the bacterial chromosomal DNA are used for direct repeat recombination excising the F factor, then the F factor brings with it chromosomal DNA, forming an F0 factor (Figure 2). The discoveries by William Hayes, Elie Wollman, and FrancËois Jacob that the F factor is a plasmid, and the subsequent discoveries of other bacterial plasmids, made possible the development of plasmid vectors for molecular cloning (Hayes, 1952; Wollman et al., 1956; Jacob and Wollman, 1958). Fs are important replicons used in single-copy gene-complementation experiments and in tests of dominance. As discussed in Hfr, the use of Hfrs for studies of bacterial recombination led tothecharacterizationofmechanismsandproteinsused in homologous genetic recombination in E. coli, and, because the DNA transferred in Hfr crosses is linear, the enzymes used in double-strand break-repair were illuminated in these studies. Descriptions of those proteins, bacterial recombination, and double-strand break-repair are given in Rec Genes, Recombination Pathways, RecA Protein and Homology, RecBCD Enzyme, Pathway, RuvAB Enzyme, RuvC Enzyme.
Further Reading
Brock TD (1990) The Emergence of Bacterial Genetics. Plainview, NY: Cold Spring Harbor Laboratory Press. Firth N, Ippen-Ihler K and Skurray RH (1996) Structure and function of the F factor and mechanism of conjugation. In: Neidhardt FC, Curtiss III R, Ingraham JL et al. (eds) Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 2, pp. 2377±2401. Washington, DC: ASM Press. Holloway B and Low KB (1996) F-prime and R-prime factors. In: Neidhardt FC, Curtiss III R, Ingraham JL et al. (eds) Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 2, pp. 2413±2420. Washington, DC: ASM Press.
680
F1 Generation
Low KB (1996) Hfr strains of Escherichia coli K12. In: Neidhardt FC, Curtiss III R, Ingraham JL et al. (eds) Escherichia coli and Salmonella: Cellular and Molecular Biology, 2nd edn, vol. 2, 2402±2405. Washington, DC: ASM Press.
References
Hayes W (1952) Recombination in E. coli K12: unidirectional transfer of genetic material. Nature 169: 118±119. Jacob F and Wollman EL (1958) Les eÂpisomes, eÂleÂments geÂneÂtiques ajouteÂs. Comptes Rendus de l'AcadeÂmie des Sciences 242: 303±306. Lederberg J and Tatum EL (1946a) Gene recombination in bacteria. Nature 158: 558. Lederberg J and Tatum EL (1946b) Novel genotypes in mixed cultures of biochemical mutants of bacteria. Cold Spring Harbor Symposia on Quantitative Biology 11: 113±114. Wollman EL Jacob F and Hayes W (1956) Conjugation and genetic recombination in Escherichia coli K12. Cold Spring Harbor Symposia on Quantitative Biology 21: 141±162.
weight, life span, fecundity, litter size, and resistance to disease and experimental manipulations. It is possible to generate organisms that are genetically uniform without suffering the consequences of whole genome homozygosity. This is accomplished by simply crossing two inbred strains to each other. The resulting F1 hybrid organisms express hybrid vigor in all of the fitness characteristics just listed with an overall life span that will exceed that of both inbred parents. Furthermore, as long as both of the parental inbred strains are maintained, it will be possible to produce F1 hybrids between the two, and all F1 hybrids obtained from the same cross will be genetically identical to each other over time and space. Of course, uniformity will not be preserved in the offspring that result from an ``intercross'' between two F1 hybrids (see Intercross); instead random segregation and independent assortment will lead to F2 animals that are all genotypically distinct.
See also: Conjugation, Bacterial; Conjugative Transposition; Hfr; Plasmids
See also: Hybrid Vigor; Intercross
F1 Generation
FAB Classification of Leukemia
Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1839
The F1 generation is the first generation resulting from a cross between two dissimilar parental lines. See also: Mendelian Genetics; Mendelian Inheritance
F1 Hybrid L Silver Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.0442
The most obvious advantage of working with inbred strains is genetic uniformity over time and space. Researchers can be confident that the inbred animals of a particular strain used in experiments today are essentially the genetic equivalent of animals from the same strain used 10 years ago. Thus, the existence of inbred strains serves to eliminate the contribution of genetic variability to the interpretation of experimental results. However, there is a serious disadvantage to working with inbred animals in that a completely inbred genome is an abnormal condition with detrimental phenotypic consequences. The lack of genomic heterozygosity is responsible for a generalized decrease in a number of fitness characteristics including body
B Bain Copyright ß 2001 Academic Press doi: 10.1006/rwgn.2001.1569
From 1976 onward, a French±American±British (FAB) cooperative group of hematologists formulated a series of classifications of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), the myelodysplastic syndromes, chronic lymphoid leukemias, and the leukemic phase of non-Hodgkin's lymphoma. These classifications were initially based only on cytology and cytochemistry, but immunophenotypic analysis was later incorporated. Subsequently it became apparent that several FAB categories of leukemia identified specific cytogenetic/molecular genetic entities, e.g., M3 AML (hypergranular promyelocytic leukemia) and L3 ALL (Burkitt's lymphoma-related acute leukemia). Other FAB categories included more than one specific cytogenetic/molecular genetic entity, e.g., M5 AML was found to include not only various acute monocytic/monoblastic leukemias associated with t(9;11)(p21-22;q23) and other translocations with an 11q23 breakpoint, but also the completely different entity, acute monoblastic leukemia associated with t(8;16)(p11;p13). The FAB classifications were important in advancing knowledge of hematological malignancies, since they provided a framework for cytogenetic and molecular genetic