Download Human Y Chromosome, Sex Determination, and Spermatogenesis

BIOLOGY OF REPRODUCTION 63, 667–676 (2000)
EDITOR’S PREFACE
The first paper in this issue of Biology of Reproduction was presented as an invited lecture at the 32nd Annual
Meeting of the Society for the Study of Reproduction (from 31 July to 3 August 1999) at Washington State University,
Pullman, WA. The lecture was part of the President’s Symposium, entitled Sexual Differentiation, organized by Dr.
Michael D. Griswold, President of the Society for the Study of Reproduction.
This paper, ‘‘Human Y Chromosome, Sex Determination, and Spermatogenesis—A Feminist View,’’ by Jennifer A.
Marshall Graves (Department of Genetics, La Trobe University, Melbourne, Victoria 3083, Australia), did not undergo
peer review. Except for minimal editorial changes, the paper is published as submitted.
Virendra B. Mahesh, Ph.D., D. Phil.
Editor-in-Chief, Biology of Reproduction
Human Y Chromosome, Sex Determination, and Spermatogenesis—
A Feminist View1
Jennifer A. Marshall Graves2
Department of Genetics, La Trobe University, Melbourne, Victoria 3083, Australia
ABSTRACT
and when this happens, the phenotype of the baby is female. Female development has therefore been said to be
the ‘‘default pathways,’’ and females have even been called
‘‘mutant males.’’
The production of a male is likely to require many more
genes than just the TDF gene. Some of these are becoming
known through studies of patients with a variety of sex
reversal syndromes. There are also likely to be many
genes—hundreds or thousands—required for germ-cell differentiation and male fertility. Of course, there are likely to
be just as many genes required for ovarian differentiation
and egg development, and so far we know rather little about
these genes or how they are switched on in the absence of
testis development.
In this review I want to argue that, far from being a macho
entity with an all-powerful role in male development, the human
Y chromosome is a ‘‘wimp.’’ It is merely a relic of the X chromosome, and most or all of the genes it bears—including the
genes that determine sex and control spermatogenesis—are relics of genes on the X chromosome that have other functions
altogether.
Sertoli cells, spermatogenesis
HUMAN SEX, GENES, AND CHROMOSOMES
In humans, as in other mammals, sex determination depends on the testis, and testis differentiation depends on the
Y chromosome.
Sex Chromosomes
Sex Determination
In mammals, the male-specific Y chromosome plays a
pivotal role in sex determination, and also bears genes that
are required for spermatogenesis. However, not all the
genes that are needed to make a testis or to make germ
cells need to be on the Y chromosome, and many are
known to be located on the X chromosome or on the autosomes (chromosomes other than the X and Y).
Like other mammals, human females have two X chromosomes (XX) and males have a single X and a single Y
chromosome (XY). The X is large (5% of the total length
of a single set of chromosomes) and bears a proportional
number of genes (3000 or 4000), which have a variety of
functions much like those of genes located on other chromosomes. To ensure fair play between the sexes, only one
X chromosome is genetically active in female cells. The set
of genes on the X chromosome is almost completely conserved between different species of eutherian (‘‘placental’’)
mammals, probably because breaking it up would disrupt
this chromosome-wide X-inactivation mechanism.
The Y chromosome is much smaller than the X chromosome and contains only a few genes. It is largely composed of repetitive sequences that preferentially bind fluo-
The event that marks human male determination is the
differentiation of the testis at about 5 wk of gestation. The
embryonic testis then churns out testosterone and Müllerian-inhibiting substance, powerful hormones that divert developmental pathways along male lines. The pivotal genetic
event is the switching of the indifferent gonad (the genital
ridge) to testis differentiation by the action of a gene called
the testis-determining factor (TDF). After this event, male
development unfolds automatically, unless something goes
wrong. A number of genetic accidents—anything from absence or mutation of TDF to a block of the action of testosterone—can interrupt the male-determining pathway,
Supported by Australian Research Council grant A00000786 and National Health and Medical Research Council (Australia) grant 980990.
2
Correspondence: Jennifer M. Graves, Department of Genetics, Building
NW7, La Trobe University, Kingsbury Drive, Bundoora, Melbourne, Victoria 3093, Australia. FAX: 613 9479 2480; e-mail: j.graves@gen.
latrobe.edu.au
1
Q 2000 by the Society for the Study of Reproduction, Inc.
ISSN: 0006-3363. http://www.biolreprod.org
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