A Life with Yeast Molecular Biology - Prof. Dr. Horst Feldmann

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The Yeast Genome Project
H. FELDMANN
In the years between 1985 and 1988, our laboratory work slowly
developed into a new phase. During their thesis work, Joachim
Hauber and Peter Nelböck-Hochstetter had used high-molecular
weight yeast DNA to clone fragments 35–40 kb in length into a
cosmid vector (pY3030) that W. Piepersberg from the Munich
Institute of Genetics had kindly provided to us. Both of them felt
that it was timely to turn to a genomic scale, dissecting the
organization of genomic entities along whole chromosomes. With
the help of a technician Peter managed to establish a cosmid
bank of 3,000 distinct clones, to prepare DNA from these by
‘‘mini-preps’’ and to fix it onto filters in a slot-blot apparatus
within 4 weeks. This procedure was repeated a second time and
we ended up with two ordered cosmid libraries in all representing
the 12.8 Mb yeast genome at P ¼ 99.99%, that is 12 times the
genome equivalent. Together with Rolf Stucka, Peter Nelböck
established a physical map of chromosome II by means of
‘‘chromosomal walking’’ and succeeded in localizing a variety of
tRNA genes, Ty elements, and genes for diverse functions.
Though these results were only published in form of doctoral
theses, somehow we had sort of a favorable undercover press,
which caused André Goffeau from Louvain-la-Neuve to ring me
up in the lab 1 day in summer 1988. He asked me whether we
would like to contribute to an assessment on ‘‘Sequencing of the
Yeast Genome’’ he was preparing for the BRIDGE Programme of
the European Communities [95]. We were enthusiastic about this
initiative and, together with Yde Steensma from Leyden,
produced an overview on how to take advantage of ordered
cosmid libraries for such an ambitious project. It is a pity that this
assessment to which a number of renowned colleagues participated,
has never been made publicly available. It contains some
ideas or predictions which never became reality, but many others
that did. André tells more details about the difficulties he
encountered when considering the launching of chromosome III
sequencing [96], which for a number of reasons had been chosen
to be the first chromosome to be tackled in 1989. After he had
solved the bureaucratic obstacles, the enterprise run rather
smoothly thanks to his untiring effort as well as that of Steve
Oliver from Manchester as the ‘‘DNA coordinator’’ and the 35
European colleagues who participated in this project. Gertrud