Science gets closer to artificial life with first synthetic chromosome

An international team of scientists have made a major breakthrough in synthetic biology (Science Magazine). For the first time ever, they were able to insert a man-made, custom-built chromosome into brewer's yeast to not only create a life form but one that also passes down its man-made genes to its offspring. We're closer to creating artificial life.

Scientists have previously made chromosomes for bacteria and viruses but this is the first time they've been able to build a chromosome for something more complex. Called eukaryotic chromosomes, they have a nucleus and are found in plants, animals and humans.

The artificial chromosome, called synIII after the chromosome three in brewer's yeast it replaced, was stitched together via a computer by a team of scientists over a period of seven years. They basically redesigned the whole damn thing piece by piece. The scientist liken man-made chromosomes to the idea that you could shuffle genes into them like a deck of cards.

The yeast cells that contained the designer chromosomes behaved as normally as, well, normal yeast cells only that they could theoretically be improved and do things normal yeast cells could not. Potentially, scientists could create man-made versions of all the chromosomes in organisms thus creating artificial life. 

ORIGINAL: Sploid

By Casey Chan

Science DOI: 10.1126/science.1249252

Total Synthesis of a Functional Designer Eukaryotic Chromosome

1. Narayana Annaluru1,*, 
2. Héloïse Muller1,2,3,4,*, 
3. Leslie A. Mitchell2,5, 
4. Sivaprakash Ramalingam1,
5. Giovanni Stracquadanio2,6, 
6. Sarah M. Richardson6, 
7. Jessica S. Dymond2,7, 
8. Zheng Kuang2, 
9. Lisa Z. Scheifele2,8,
10. Eric M. Cooper2, 
11. Yizhi Cai2,9, 
12. Karen Zeller2, 
13. Neta Agmon2,5, 
14. Jeffrey S. Han10, 
15. Michalis Hadjithomas11,
16. Jennifer Tullman6, 
17. Katrina Caravelli2,12, 
18. Kimberly Cirelli1,12, 
19. Zheyuan Guo1,13, 
20. Viktoriya London1,13,
21. Apurva Yeluru1,13, 
22. Sindurathy Murugan6, 
23. Karthikeyan Kandavelou1,14, 
24. Nicolas Agier15,16, 
25. Gilles Fischer15,16,
26. Kun Yang2,6, 
27. J. Andrew Martin2,5, 
28. Murat Bilgel13, 
29. Pavlo Bohutski13, 
30. Kristin M. Boulier12, 
31. Brian J. Capaldo13,
32. Joy Chang13, 
33. Kristie Charoen13, 
34. Woo Jin Choi13, 
35. Peter Deng11, 
36. James E. DiCarlo13, 
37. Judy Doong13, 
38. Jessilyn Dunn13,
39. Jason I. Feinberg12, 
40. Christopher Fernandez12, 
41. Charlotte E. Floria12, 
42. David Gladowski12, 
43. Pasha Hadidi13,
44. Isabel Ishizuka12, 
45. Javaneh Jabbari12, 
46. Calvin Y. L. Lau13, 
47. Pablo A. Lee13, 
48. Sean Li13, 
49. Denise Lin12,
50. Matthias E. Linder12, 
51. Jonathan Ling13, 
52. Jaime Liu13, 
53. Jonathan Liu13, 
54. Mariya London12, 
55. Henry Ma13, 
56. Jessica Mao13,
57. Jessica E. McDade13, 
58. Alexandra McMillan12, 
59. Aaron M. Moore12, 
60. Won Chan Oh13, 
61. Yu Ouyang13, 
62. Ruchi Patel13,
63. Marina Paul12, 
64. Laura C. Paulsen13, 
65. Judy Qiu13, 
66. Alex Rhee13, 
67. Matthew G. Rubashkin13, 
68. Ina Y. Soh12,
69. Nathaniel E. Sotuyo12, 
70. Venkatesh Srinivas13, 
71. Allison Suarez13, 
72. Andy Wong13, 
73. Remus Wong13, 
74. Wei Rose Xie12,
75. Yijie Xu13, 
76. Allen T. Yu12, 
77. Romain Koszul3,4, 
78. Joel S. Bader2,6, 
79. Jef D. Boeke2,11,5,†, 
80. Srinivasan Chandrasegaran1,†

Author Affiliations

1. ¹Department of Environmental Health Sciences, Johns Hopkins University (JHU) School of Public Health, Baltimore, MD 21205, USA.
2. ²High Throughput Biology Center, JHU School of Medicine, Baltimore, MD 21205, USA.
3. ³Group Spatial Regulation of Genomes, Department of Genomes Genetics, Institut Pasteur, F-75015 Paris, France.
4. ⁴CNRS, UMR 3525, F-75015 Paris, France.
5. ⁵New York University Langone Medical Center, New York, NY 10016, USA.
6. ⁶Department of Biomedical Engineering and Institute of Genetic Medicine, Whiting School of Engineering, JHU, Baltimore, MD 21218, USA.
7. ⁷Biological Sciences, Research and Exploratory Development Department, JHU Applied Physics Laboratory, Laurel, MD 20723, USA.
8. ⁸Department of Biology, Loyola University Maryland, Baltimore, MD 21210, USA.
9. ⁹University of Edinburgh, Edinburgh, Scotland, UK.
10. ¹⁰Carnegie Institution of Washington, Baltimore, MD 21218, USA.
11. ¹¹Department of Biology, JHU, Baltimore, MD 21218, USA.
12. ¹²Krieger School of Arts and Sciences, JHU, Baltimore, MD 21218, USA.
13. ¹³Whiting School of Engineering, JHU, Baltimore, MD 21218, USA.
14. ¹⁴Pondicherry Biotech Private Limited, Pillaichavady, Puducherry 605014, India.
15. ¹⁵Sorbonne Universités, Université Pierre et Marie Curie, Univ Paris 06, UMR 7238, Génomique des Microorganismes, F-75005 Paris, France.
16. ¹⁶CNRS, UMR7238, Génomique des Microorganismes, F-75005 Paris, France.

ABSTRACT

Rapid advances in DNA synthesis techniques have made it possible to engineer viruses, biochemical pathways and assemble bacterial genomes. Here, we report the synthesis of a functional 272,871–base pair designer eukaryotic chromosome, synIII, which is based on the 316,617–base pair native Saccharomyces cerevisiae chromosome III. Changes to synIII include TAG/TAA stop-codon replacements, deletion of subtelomeric regions, introns, transfer RNAs, transposons, and silent mating loci as well as insertion of loxPsym sites to enable genome scrambling. SynIII is functional in S. cerevisiae. Scrambling of the chromosome in a heterozygous diploid reveals a large increase in a-mater derivatives resulting from loss of the MATα allele on synIII. The complete design and synthesis of synIII establishes S. cerevisiae as the basis for designer eukaryotic genome biology.