Artificial Chromosomes


Yeast, bacterial and mammalian artificial chromosomes can clone and transfer genes or other genomic DNA segments into cells in the form of additional supernumerary chromosomes. They provide a route to the analysis of chromosome dynamics, long‐ and short‐range regulation of genes and possibly to gene therapy.

Keywords: yeast artificial chromosomes; mammalian artificial chromosomes; chromosome; centromere; gene therapy

Figure 1.

Yeast artificial chromosomes (YACs) and mammalian artificial chromosomes (MACs). The structure of a typical YAC compared with one of the current formulations of a MAC. (a) The YAC includes sequences for a centromere (CEN4), an origin of replication (ARS) and telomeres (TEL) at its ends. The two vector ‘arms’ also contain selectable markers for tryptophan (TRP1) and uracil (URA3) utilization in the original and still frequently used pYAC4 (Burke et al., ); a genomic DNA insert of up to 1 Mb is sealed in place by ligase during the cloning step, and the YAC is then transformed into host yeast cells. (b) Current MACs contain human TEL sequences, arrays of alphoid sequences or centromeric DNA as a CEN equivalent and selectable markers (A and B), as well as a genomic DNA insert like that of YACs. Functional origins of replication are usually left out of the vector, because they occur spontaneously every few hundred kilobases in human or mouse DNA.



Brownstein BH, Silverman GA, Little RD, et al. (1989) Isolation of single‐copy human genes from a library of yeast artificial chromosome clones. Science 244: 1348–1351.

Burke DT, Carle GF and Olson MV (1987) Cloning of large segments of exogenous DNA into yeast by means of artificial chromosome vectors. Science 236: 806–812.

Cocchia M, Kouprina N, Kim SJ, et al. (2000) Recovery and potential utility of YACs as circular YACs/BACs. Nucleic Acids Research 28: 81.

Friedmann T (2000) Medical ethics: principles for human gene therapy studies. Science 287: 2163–2165.

Kouprina N, Annab L, Graves J, et al. (1998) Functional copies of a human gene can be directly isolated by transformation‐associated recombination cloning with a small 3′ end target sequence. Proceedings of the National Academy of Sciences of the United States of America 95: 4469–4474.

Kuroiwa Y, Tomizuka K, Shinohara T, et al. (2000) Manipulation of human minichromosomes to carry greater than megabase‐sized chromosome inserts. Nature Biotechnology 18: 1086–1090.

Moyzis RK (1991) The human telomere. Scientific American 265: 48–55.

Murray AW and Szostak JW (1983) Construction of artificial chromosomes in yeast. Nature 305: 189–193.

Rosenberg LE and Schechter AN (2000) Gene therapist, heal thyself. Science 287: 1751.

Tomizuka K, Yoshida H, Uejima H, et al. (1997) Functional expression and germ line transmission of a human chromosome fragment in chimeric mice. Nature Genetics 16: 133–143.

Willard HF (1998) Centromeres: the missing link in the development of human artificial chromosomes. Current Opinion in Genetics and Development 2: 219–225.

Yang XW, Wynder C, Doughty ML and Heintz N (1999) BAC‐mediated gene‐dosage analysis reveals a role for Zipro1 (Ru49/Zfp38) in progenitor cell proliferation in cerebellum and skin. Nature Genetics 22: 327–335.

Further Reading

Ebersole TA, Ross A, Clark E, et al. (2000) Mammalian artificial chromosome formation from circular alphoid input DNA does not require telomere repeats. Human Molecular Genetics 9: 1623–1631.

Friedmann T (2000) Changing roles for academia and industry in genetics and gene therapy. Molecular Therapy: The Journal of the American Society of Gene Therapy 1: 9–11.

Henning KA, Novotny EA, Compton ST, et al. (1999) Human artificial chromosomes generated by modification of a yeast artificial chromosome containing both human alpha satellite and single‐copy sequences. Proceedings of the National Academy of Sciences of the United States of America 96: 592–597.

Huertas D, Howe S, McGuigan A and Huxley C (2000) Expression of the human CFTR gene from episomal oriP‐EBNA1‐YACs in mouse cells. Human Molecular Genetics 9: 617–629.

Ikleno M, Grimes B, Okazaki T, et al. (1998) Construction of YAC‐based mammalian artificial chromosomes. Nature Biotechnology 16: 431–439.

de Jong G, Telenius AH, Telenius H, et al. (1999) Mammalian artificial chromosome pilot production facility: large‐scale isolation of functional satellite DNA‐based artificial chromosomes. Cytometry 35: 129–133.

Shen MH, Mee PJ, Nichols J, et al. (2000) A structurally defined mini‐chromosome vector for the mouse germ line. Current Biology 10: 31–34.

Vos JM (1998) Mammalian artificial chromosomes as tools for gene therapy. Current Opinion in Genetics and Development 3: 351–359.

Willard HP (2000) Artificial chromosomes coming to life. Science 290: 1308–1309.

Yang XW, Model P and Heintz N (1997) Homologous recombination‐based modification in Escherichia coli and germ line transmission in transgenic mice of a bacterial artificial chromosome. Nature Biotechnology 15: 859–865.

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How to Cite close
Schlessinger, David, and Nagaraja, Ramaiah(Jan 2006) Artificial Chromosomes. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0005806]