Table Of ContentMECHANISMS
OF GENETIC
RECOMBINATION
STUDIES IN SOVIET SCIENCE
LlFE SCIENCES
1973
Motile Muscle and Cell Models
N. I. Arronet
Pathological Effects of Radio Waves
M. S. Tolgskaya and Z. V. Gordon
Central Regulation of the Pituitary-Adrenal Complex
E. V. Naumenko
1974
Sulfhydryl and Disulfide Groups of Proteins
Yu. M. Torchinskii
Organ Regeneration: A Study of Developmental Biology in Mammals
L. D. Liozner
Mechanisms of Genetic Recombination
V.V.Kushev
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STUD~SINSOWETSC~NCE
MECHANISMS
OFGENETIC
RECOMBINATION
V.V.Kushev
A. F. loffe Physicotechnical Institute
Academy of Sciences of the USSR
Leningrad, USSR
Translated from Russian by
Basil Haigh
Springer Science+Business Media, LLC
Library of Congress Cataloging in Publication Data
Kushev, Vladislav Valer'fanovich.
Mechanisms of genetic recombination.
(Studies in Soviet sciencel
Translation of Mekhanizmy genetischeskol rekombinatSii.
Bibliography: p.
1. Genetic recombination. I. Title. 11. Series.
QH443.K8813 575.1 73·83898
ISBN 978-1-4757-5802-3 ISBN 978-1-4757-5800-9 (eBook)
DOI 10.1007/978-1-4757-5800-9
Vladislav Valer'yanovich Kushev was born in 1939 in Leningrad. In 1963 he
was graduated from the Department of Genetics, Leningrad University. He
has specialized in the study of the mechanism of genetic recombination in
transformation of bacteria and is the author of more than ten publications on
this sUbject. He is now engaged in research at the Laboratory of Biopolymers
at the Leningrad Institute of Nuclear Physics.
The original Russian text, published by Nauka Press in Leningrad in 1971, has
been corrected by the author for the present edition. This translation is pub
lished under an agreement with the Copyright Agency of the USSR (VAAP).
MEXAHH3Mhl rEHETHqECHOH PEHOMBHHAllHH
B. B. HYllieB
MEKHANIZMY GENETICHESKOI REKOMBINATSII
V. V. Kushev
© 1974 Springer Science+Business Media New York
Originally published by Consultants Bureau, New York in 1974.
Softcover reprint of the hardcover 1s t edition 1974
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or trans
mitted, in any form or by any means, electronic, mechanical, photocopying,
microfilming, recording, or otherwise, without written permission trom the
Publisher
"Recombination is a basic biological process;
to und erstand its molecular basis is clearly
a tough and exciting challenge."*
G. Pontecorvo
Preface
"Genetic recombination" is the name given to the redistribution of
information inherited from the parents in the progeny. Although this defi
nition applies to the recombination of both linked and nonlinked genes,
the term "recombination " is usually applied in a narrower sense, to mean
only recombination of linked markers (between different genes and within
the same gene). It is in this sense that the term is used both in the title of
the book and in the text (except Section 1.1).
Recombination of nonlinked genes is based on a mechanism of free
combination of chromosomes in meiosis. Recombination of linked genes
usually takes place by crossing-over of chromosomes. Recombinations with
in the same gene are in most cases (if not always) the result of conversion
of one of the alleles into the other, a process known as gene conversion. In
crossing-over there is a reciprocal exchange of information between homol
ogous chromosomes, while in conversion this exchange is predominantly
nonreciprocal in character.
Genetic recombination is a fundamental property of allliving systems
starting from the RNA-containing viruses (Kawai and Hanafusa, 1972) and
ending with higher plants and animals. As the source of variation through
combination, genetic recombination is one of the principal factors in evo
lution. At the same time, however, results showing that genetic recombina
tion is one of the main sources of variation through mutation have also
been described. Recombination mechanisms, according to some investiga
tors, may also lie at the basis of variation within the organism and to take
part in such processes as the formation of antibodies, of communicative
proteins, and so on. The link discovered recently between mechanisms of
recombination and cell repair has converted the study of the mechanism of
genetic recombination from a purely internal problem of genetics into a
*Genetics Today, Vol. 2, New York and London, p. 89.
v
vi PREFACE
general problem of molecular biology. Enzyme systems responsible for
recombination have been found to take part in such fundamental processes
as the correction of mistakes in the genetic text. It is not surprising, there
fore, that the serious study of the molecular mechanism of recombination
should have begun only a few years ago. Not until more elementary matters
had been explained was it possible to make an approach to this complex
problem. To begin with, the structure of the elements interacting during
recombination (DNA molecules and chromosomes) had to be established,
and the method of their replication had then to be explained; the biological
properties of many new parasexual systems (bacteriophages; conjugation,
transformation, transduction, sexduction in bacteria) had to be carefully
studied; if not the nature of chromosome-pairing processes, at least the
moment of conjugation of the chromosomes in meiosis had to be deter
mined; the structure of the recombinant molecules studied; and, finaIly,
the character of the recombination process discovered. All this had to be
done, of course, on a basis of the achievements of cIassical genetics, which
had yielded strict and final proof of the chiasmatype theory.
However, despite evident and rapid progress, we are still only halfway
to our goal. During the crisis of the naively optimistic views on the nature
of recombination (the mechanical crossing-over hypothesis), which began
with "splitting" of the gene, new facts were discovered which could not be
explained fully at that time by contemporary physicochemical and bio
chemical concepts of crossing-over. Facts of this type incIuded high negative
interference, gene conversion, the polarity and allele specificity of recom
bination within the gene, the nonadditive and even linear character of the
ultrashort distances, and so on. Proof that recombination within the gene
is intimately connected with crossing-over indicates that it takes place at the
sites of breaking and rejoining of the chromosomes. In this connection the
facts obtained by the study of recombination within the gene, especially by
the use of tetrad analysis, provide extremely valuable material for a con
struction of a general theory of crossing-over.
Many thousands of investigations have been undertaken in order to
study the mechanism of genetic recombination, starting with the work of
Morgan and continuing until the present time. The fIow of publications has
now increased so rapidly and the fields of research have widened so consid
erably that there is now an absolute need for a survey of the problem in
toto. An attempt is rpade in this book to generalize the results obtained in
genetic systems of different complexity from phages to mammals. This
approach may appear unduly rash, but the universality of the fundamental
metabolic processes revealed by molecular biology inspires confidence that
the fundamental mechanisms of genetic recombination are also universal
for the whole living kingdom. Specific differences undoubtedly exist, but it
PREFACE vii
will be more useful to find the general principles first and then to go on to
explain the exceptions and to define the limitations.
At the same time the book cannot claim to be an exhaustive survey of
the literature which has accumulated since the publication of the last mono
graph on this problem (Stern, 1933). Moreover, many of the facts and hy
potheses which, in the present writer's opinion, lie outside the mainstream
of development of ideas on the mechanism of genetic recombination have
simply been omitted. No attempt likewise is made to analyze special cases
of genetic recombination such as lysogenization the formation of special
ized transducing phage particles and F factors; transposition of the dis
sociating element (Ds) in corn, recombination of the factors determining
the type of conjugation in Schizophyllum commune, etc.
The principle used in the planning of this book, progressing from facts
to hypotheses on the historical plane, must certainly make it more difficult
to read because it is much easier to examine facts from the stand point of a
preexisting scheme. However, since no general theory of crossing·~>ver has
yet been developed, the book must inevitably be of this character. Modern
theories of crossing-over are described only in the last chapter, Chapter 5.
This chapter is entirely theoretical and speculative in character. The funda
mental facts on which the corresponding speculations are developed are
described in the first four chapters.
In Chapter I the birth and development of recombination analysis
are briefly described with respect to recombination between genes. The
chiasmatype theory of Janssens and Morgan is examined in detail, together
with alternative hypotheses for the mechanism of crossing-over; breakage
and reunion and copy-choice both in the classical form and in its modern
modifications.
Facts leading to a crisis in the classical views of the mechanism of
recombination and also a number of hypotheses put forward in an attempt
to explain these facts within the framework of modified classical ideas are
considered in Chapters 2 and 3.
The structure of chromosomes, the method of their replication, and
identification of the stages of DNA synthesis, of crossing-over, and of con
version in meiosis are discussed in Chapter 4. Modern physicochemical,
genetic, and biochemical results supporting the mechanism of breaking and
rejoining and of the participation of enzyme systems in recombination are
given. The possible mechanisms of induced crossing-over and of structural
changes in chromosomes are also discussed.
Facts obtained by the study of recombinatioll within the gene are in
terpreted in Chapter 5, and the problem of molecular heterozygosis is ana
lyzed. The two principal groups of models of recombination are discussed.
The first group includes models with statistical breaks and exonucleotic
vüi PREFACE
repair, the second group models with fixed points of breaks and endonu
cleotic repair (correction). In my view the process of recombination can be
adequately described by adoption of the principle of directed correction.
Many readers will not find here a detailed analysis of the systems with
which they are working. However, this book would never have been written
if I had not limited my task to the examination of only the most general
problems. It likewise would never have seen the light of day without the
help, support, and good advice of many people to whom I am deeply grate
ful: I. A. Zakharov, M. I. Mosevitskii, R. A. Kreneva, V. L. Kalinin, Z. V.
Kusheva, I. E. Vorobtsova, and, in particular, S. E. Bresler.
I am indebted to Plenum Press for allowing me to update the text with
material obtained in the last two years, which has added about 300 new
titles to the bibliography. I warmly acknowledge the interest shown by
R. Holliday and J. Scaife in the progress of the English edition of this book.
V.V. K.
Leningrad
June, 1973
Contents
Chapter 1. Recombination of Genes ........................... 1
1.1 Mendelism........................................... 1
1.2 Sutton's Prophecy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.3 The First Hypothesis of Recombination of Linked Genes. . . . . . 5
1.4 The Chiasmatype Theory of Janssens ..................... 5
1.5 Morgan's Experiments on Drosophila ..................... 7
1.6 The Genetic Map . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
1.7 Interference......................................... 11
1.8 The Physica1 Scale of Genetic (Linkage) Maps . . . . . . . . . . . . . .. 13
1.9 Chromatid Crossing-over. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 14
1.10 The Problem of Chromatid Interference ................... 17
1.11 Chiasmata and Crossing-over . . . . . . . . . . . . . . . . . . . . . . . . . . .. 20
1.12 Cyto10gica1 Evidence for Crossing-over. . . . . . . . . . . . . . . . . . . .. 21
1.13 Darlington's Hypothesis ............................... 22
1.14 Belling's Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 23
1.15 Sister-Strand Exchanges ............................... 24
1.16 Mitotic Crossing-over. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 27
1.17 Merozygote Systems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 27
1.18 Recombination in Bacteriophages . . . . . . . . . . . . . . . . . . . . . . .. 31
1.19 The Copy-Choice Hypothesis ........................... 33
1.20 Conc1usion ......................................... 35
Chapter 2. Intragenie Recombination. Random-Samp1e Analysis. . . .. 37
2.1 The Concept of the Gene. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 37
2.2 Step Allelism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 39
2.3 Pseudoallelism....................................... 39
2.4 Intragenie Recombination . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 41
2.5 The Structure of the Gene. . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 42
2.6 The Recon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 46
ix
