Download Evolution of the Y Sex Chromosome in AnimalsY chromosomes

Evolution of the Y Sex
Chromosome in Animals
Y chromosomes evolve through the degeneration of autosomes
William R. Rice
S
ex chromosomes are part of the
gender determination system of
many organisms. They are common in animals and rare in plants.
There are many forms of sex determination. Gender may be determined genetically or in response to
environmental cues such as temperature or social circumstance. Genetic
sex determination is typically expressed in the developing zygote but
can also be mediated maternally,
with some females producing only
daughters and others only sons.
Zygotic sex determination has
~ many forms. In bees, ants, and wasps
fertilized eggs develop into females
and unfertilized eggs into males. In
the guppy, and many other fish, invertebrates, and plants, gender is
determined by the presence or absence of a sex determining gene (G,
or a cluster of tightly linked genes);
Gg is male and gg female. The heterozygous (i.e., heterogametic) sex
can be female or male, depending on
the species. Gender can also be determined by specialized sex chromosomes (X and Y). In mammals, females are XX and males are XY; in
birds, females are XY (sometimes
designated ZW) and males are XX
(sometimes designated ZZ); and in
nematodes, females are XX and
males are XO, in which
denotes
the absence of a homologous chromosome. More than two sex chromosomes are found in some species,
°
William R. Rice is a professor in the Biology
Department, University of California, Santa
Cruz, CA 95064. © 1996 American Institute
of Biological Sciences.
May 1996
Y chromosome
evolution is a model
system for the
adaptive sigificance of
sexual recombination
in whole organisms
but these are complex derivatives of
the familiar XX/XY system. Sex determination and sex chromosomes
are sometimes, but not always, associated with a dosage compensation
mechanism, such as X inactivation,
which ensures equal gene expression
in the XX and XY sex.
In this article I focus on the Y sex
chromosome of animals. I first describe the major distinguishing characteristics of the Y and the steps in its
evolution from a nonsex chromosome (autosome). Next, I present the
genetic theory developed to account
for the Y's evolution. I then offer an
overview of recent experiments that
test the theory and discuss two experimental approaches for studying
Y chromosome evolution. In the first
approach, used in my own laboratory, a combination of artificial selection and visible genetic markers
is used to create synthetic sex-determining genes and Y chromosomes,
which are in turn used to experimentally simulate the early stages of Y
chromosome evolution. The second
approach is taken by Manfred
Steinemann's and Sigrid Steinemann's group, whose molecular studies of a naturally occurring Y chromosome permit certain molecular
aspects of its evolution to be directly
observed. Finally, I place the work
on the Y chromosome in a broader
context by considering the Y chromosome as a model system for the
study of the adaptive significance of
sexual recombination in whole orgarusrns.
The Y sex chromosome
Two properties distinguish the Y
chromosome from an ordinary autosome: Recombination with its homolog, the X chromosome, is absent
or restricted to a small region, and it
has highly reduced genetic activity
within the nonrecombining region.
Consider humans as an example.
Both sexes have two copies of each of
the 22 autosomal chromosome types
plus a pair of sex chromosomes.
Males ha ve an X and a Y sex chromosome (XY), whereas females have two X
chromosomes (XX). In most respects
the human X is organized genetically like an autosome. Its major
distinction is that it undergoes dosage compensation, a phenomenon
whereby, in females, most genes on
one of the X chromosomes are inactivated, whereas these same genes
on the single active X chromosome
are transcribed at twice the rate than
they would be on an autosome. In
males, X chromosomes are also
hyperactivated, in this case not to
make up for an inactivated X but to
offset the genetic inertness of the Y
331
over most of its length.
Molecular studies (summarized in
Wachtel 1994)suggestthatthe human
Y chromosome is nearly devoid of
functional genes; in contrast, many
hundreds of genes have been found
on the X chromosome. Some genes
found on the tip of the Y chromosome (the pseudoautosomal region)
recombine with homologous genes
on the X chromosome. The remaining genes are in the nonrecombining
portion of the Y (the "differential
segment," which constitutes most of
the Y chromosome). To date, the
male-limited differential segment of
the Y chromosome has been demonstrated to contain the Sry gene,
which causes development to follow
the male rather than the female pathway; one or a few genes necessary
for male fertility; and several other
genes that appear to be unrelated to
sex determination and fertility. New
Y-linked genes may be found in the
future, but it is clear that most genes
located on the X chromosome are
absent from the nonrecombining portion of the Y chromosome. What
evolutionary processes led to dimorphic X and Y sex chromosomes?
Stages ofY
chromosome evolution
Comparative studies across many
taxa indicate that the Y has evolved
independently from an ordinary au tosome many times in many different taxonomic lineages (see for review Bull 1983, Mitwoch 1967). I
focus on the evolutionary processes
that contributed to the transition from
an ordinary autosome into the degenerate Y chromosome in animals,
although most of the same principles
also apply to plants (Charlesworth
[1991] reviews additional information on plants).
Because Y chromosomes appear
to have evolved slowly over millions
of years, direct observation of the
steps by which the Y chromosome
evolved from an ordinary autosome
is impossible . A working hypothesis
can be developed, however, from
animals such as fish, in which the Y
chromosome has evolved independently many times. The Y chromosome began to evolve at different
times in different lineages, so Y chromosome evolution is at different
332
Ordinaryautosomes
y
X
y
y
X
X
y
X
Polygeni c sex
determination
I
Her ma phr odite
~
Genic sex
determination
Semlchro mo so mal
sex
determination
Ch
I
romosoma
.
.
eterm lnatt on
~ex
XO sex
determination
Environmental
sex det ermination
Figure 1. Proposed pathway for the evolution of the Y sex chromosome in animals.
The model is based on observations of different fish species. The most primitive Y
chromosome carries a dominant gender-determining allele (G) that is associated
with genic sex determination . A nonrecombining differential segment then arises
surrounding the G locus (shading indicates nonrecomb ining region), giving rise to
semichromosomal sex determination . Genetic deterioration of the differential
segment of the Y chromosome then selects for dosage compensation (striped
region-these genes are expressed at double-speed) on the corresponding portion
of the X chromosome. Dosage compensation occurs in mammals and many other
groups but appears to be absent in birds and ha s not been studied in fish. Expansion
of the differential segment leads to chromosomal sex determination. Extensive
deterioration of the nonrecombining Y chromosome may ultimately lead to its
complete loss, in XO sex determ ination.
stages in different extant species.
By ordering the variety of Y chromosome types found in extant fish
species, Kirpichnikov (1981) was able
to construct a trajectory, shown in
Figure 1, going from primitive (most
similar to a typical autosome) to
advanced (nonrecombining and lack ing most or all genetic funct ion)
stages. The major steps in Y chromosome evolution in other groups of
animals are thought to be similar,
although this extrapolation is tentative because in most other groups of
animals (e.g., mammals), most of
the intermediate steps are no longer
pre sent in extant species.
Kirpichnikov's (1981) overview of
the genetics of sex determination in
fish provides comparative evidence that
hermaphroditism, in which each individual has both male and female
function, is the primitive state. The
first stage in the evolution of a Y
chromosome is the evolution of genic
sex determination, in which a single
dominant factor (G) determines gender. This dominant factor may be a
single dominant allele or a collection of tightly linked genes, but for
simplicity let us assume that G is a
single dominant allele. We will also
assume for simplicity that males are
the heterogametic sex (Gg, produc-
ing two types of haploid gamete, G
or g) and females the homogametic
sex (gg, producing only g gametes).
Although males are most commonly
the heterogametic sex, in those cases
in which females are the heterogametic sex the same principles apply.
The next stage in Y chromosome
evolution is semichromosomal sex
determination. Here the Y chromosome stops recombining with the X
in a limited region (the differential segment) surrounding the G allele. Because recombination no longer homogenizes the genetic information
in this region, for reasons described
below, the Y-linked differential segment is free to diverge in sequence
from the homologous region on the
X. As th e differential segment becomes larger, for reasons described
below, the X and Y chromosomes
diverge to a greater extent. Once the
differential segment constitutes all,
or virtually all , of the Y chromosome, the system is referred to as
chromosomal sex determination.
The inviability of experimentally
produced YY males in a number of fish
specieswith small differential segments
suggests that the Y begins to degenerate soon after a differential segment is
formed (reviewed in Kirpichnikov
1981). Once the chromosomal stage
BioScience Vol. 46 No.5
is reached, continued degeneration
of the Y ultimately erodes virtually
all of its genetic activity, thereby
permitting it to be lost altogether, as
occurs in XO sex determination.
Reversals in the trajectory depicted in Figure 1 can occur. For
example, chromosomal sex determination may be converted back to
semichromosomal sex determination
by the translocation of a large piece
of an autosome onto the Y chromosome. The trajectory may also arrest
at certain stages for long periods of
evolutionary time. For example, the
conversion from XY to XO sex determination has not been observed in
some lineages. (Other, more complex forms of sex chromosomes, such
as multiple sex chromosomes [XXY
or XYY], also can evolve, but these
are not reviewed here; Bull 1983.)
From the deduced sequence of
events in Figure 1, two factors appear to be critical in the evolution of
the Y chromosome: elimination of
recombination between the X and Y
chromosomes due to continual expansion of the differential segment,
followed by gradual degeneration of
this region. What factors lead to
suppressed recombination and degeneration of the Y chromosome?
Theory for the evolution of
suppressed recombination
There are two major hypotheses for
the evolution of suppressed recombination between the X and Y chromosomes. One is Nei's (1969) extension
of Haldane's (1922) earlier suggestion that if there were multiple sexdetermining loci on a single chromosome and if some intermediate
genotypes were prone to becoming
infertile intersexes, then natural selection would favor the elimination
of recombination between the contributing loci. Recombination is selected against because it is likely to
continually generate the genotypes
producing infertile intersexes. This
hypothesis is actually a special case
of the second hypothesis, which is
based on the accumulation of sexually antagonistic alleles at loci that
are tightly linked to the gender-determining locus (sexually antagonistic genes hypothesis; Bull 1983, Fisher
1931, Rice 1987a). Sexually antagonistic genes are loci with allelic variMay 1996
ants that are favored in one sex but ally antagorusnc allele, no matter
disfavored in the other.
how detrimental to females, is likely
The sexually antagonistic genes to accumulate on a primitive Y chrohypothesis was motivated by early mosome. To see why, consider a
genetic mapping studies of the guppy, male-benefit sexually antagonistic
a common aquarium fish with genic allele introduced by mutation just
sex determination (or an undetected one map unit (1 cM) away from the
small differential segment). Males G allele. In this case the new mutant
are highly ornamented, with a vari- allele will co segregate with the G
ety of traits, such as bright body allele 99% of the time and therefore
color, long tails, and flashy spots of will almost always be transmitted to
varying color, size, and position. sons, where it is favored. Only 1 % of
When the pioneering geneticist Winge the time will it cross over to the
(1927) mapped 18 major genes pro- primitive X chromosome and be
ducing these ornamental character- transmitted to daughters, where it is
istics, he was surprised to find that disfavored.
17 were located on the sex chromoTight linkage to the G allele theresomes. Moreover, all of these were fore generates sex-biased gene translocated within two recombinational mission, which greatly facilitates the
map units (centimorgans [cM]) of accumulation of male-benefit sexually
the male-determining factor. This antagonistic mutations, even when they
clustering of genes controlling unre- are highly deleterious to females and
la ted traits is unlikely to occur by trivially beneficial to males (see Bull
chance because the guppy, like hu- 1983, Rice 1987a, for quantitative demans, has 23 pairs of small chromo- tails). As a consequence, the constraints
somes. Winge concluded that some- for the accumulation of male-benefit
thing about the region near the sexually antagonistic mutations are far
gender-determining locus makes it a more permissive in the vicinity of a
"hot spot" for ornamentation genes. gender-determining locus than at ordiWhat is the evolutionary basis of nary locations within the genome. The
the hot spot? Fisher (1931) was fa- result is the disproportionate accumumiliar with Winge's results and pro- lation of sexually antagonistic alleles
posed a simple model based on sexu- near a major sex-determining locus.
ally antagonistic genes. Fisher Hence the chromosomal region immecorrectly assumed that genes caus- diately adjacent to a gender-detering ornate characters, when ex- mining locus should be a hot spot for
pressed in both sexes, as is likely to sexually antagonistic genes.
be the case early in their evolution,
Once sexually antagonistic alleles
would be favored in males but disfa- begin to accumulate on the primitive
vored in females (see Bischoff et al. Y chromosome near a gender-deter1985, Endler 1980). In both sexes, mining locus, they are likely to conthe ornamental characteristics would tinually cross over to the X chromake the fish more conspicuous to mosome (at a low rate for each
predators and in that respect would generation but with substantial cube disadvantageous. However, or- mulative impact). This crossing over
nate males, but not the ornate fe- creates a genetic load in females (or,
males, have a substantial mating more generally, the heterogametic
advantage, which can outweigh the sex). There are two evolutionary
predation disadvantage. Alleles pro- ways to counter this load: sex-limducing ornamental characteristics ited gene expression, which prevents
are therefore termed male-benefit the trait from being expressed in
sexually antagonistic alleles.
females, and suppressed recombinaGenetic theory predicts that at tion near the G allele, which keeps
most locations within the genome, the sexually antagonistic allele on
sexually antagonistic alleles will the Y chromosome and out of feaccumulate in the gene pool only males. Because both outcomes elimiwhen they proffer a net selective nate the genetic load in females, the
advantage, that is, when the advan- accumulation of sexually antagonistage to one sex is larger than the tic alleles ini tiates a race between
disadvantage to the other. At loci these two alternative evolutionary
tightly linked to the G allele, how- pathways.
Sex-limited gene expression is a
ever, virtually any male-benefit sexu333
a
b
c
d
e
f
the observed reduction in recombination rate. No reduction in recombination rate was found in the chromosomal region flanking that
selected for reduced recombination,
demonstrating a highly localized response to selection.
This study, along with other studies using D. melanogaster, suggests
that suppressed recombination near
a sex locus can evolve rapidly and
that the evolution of reduced recombination will frequently win the race
against sex-limited gene expression.
If suppressed recombination does
evolve near the
G allele on the
primitive Y chromosome, then, at
least in theory, this suppression can
in itiate a genetic cha in reaction that
gradually eliminates recombination
along all or most of the Y (sexually
antagonistic genes chain reaction
model; Figure 2) . Whether this genetic model explains the breakdown
in recombination between the X and
Y chromosomes depends cr itically
on the availability of two types of
genetic variation: that for localized
suppression of recombination and
that for sexuaIIy antagonistic alleles . The requisite va riation for localized suppression of recombination
has been found to be abundant in the
only model system (D. melanogaster)
in which it has been systematically
sought. But are sexually antagonistic alleles also common enough to
drive the genetic ch ain reaction?
Figure 2. The sexually antagonistic genes chain reaction model leads to the gradual
elimination of recombination between the X and Y chromosomes. (a) A primitive
Y chromosome differentiated from the X chromosome only by the G allele at a maledetermining locus. The G locus is placed near the end of the chromosome to simplify
the diagram. (b) The presence of the G allele creates a hot spot where male-benefit
sexually antagonistic alleles accumulate more readily. Mutation produces malebenefit sexually antagon istic alleles at loci located throughout the chromosome. (c)
A male-benefit sexually antagonistic allele (aSA ) accumulates within the hot spot,
selecting for reduced recombination in the chromosomal region (G-a SA ) ' (d) Evolution of suppressed recombination in the shaded interval G-a SA causes linkage to the
G allele to become tighter at downstream loci, extending the length of the hot spot .
(e) An additional male-benefit sexually antagonistic allele (bSA ) accumulates in the
newly generated hot spot region, and this allele selects for reduced recombination
in the region a sA-b sA' (f) Evolution of suppressed recombination in the region a sA-b sA
further extends the hot spot, continuing a chain reaction in which the accumulation Recent experiments on sexually
of sexually antagonistic alleles reduces recombination and reduced recombination antagonistic genes
enhances the accumulation of sexually antagonistic alleles.
To directly test whether sexuaIIy
antagonistic aIIele s would accumucomplex adaptation that, for ex- suppression of recombination has late in the vicinity of a major sex ample, requires the evolution of sex- been shown to be common in Droso- determin ing gene on a p rimitive Y
specific regulatory sequences (e.g., phila melanogaster (Brooks and chromosome, I used sex-specific arthose that bind sex hormones) near Marks 1986, Charlesworth and tificial selection to convert an autothe sexually antagonistic aIIele. It Charlesworth 1985, Chinicci 1971). somal dominant eye color aIIele into
therefore is expected to evolve For example, after 33 generations of a new, synthetic female-determining
slowly. By contrast, localized sup- selecting for reduced recombination aIIele (Sfd aIIele, Figure 3; Rice 1992):
pression of recombination can evolve within a 15.4-centimorgan region of Any fly heterozygous for th is domifar more rapidly, at least when the the X chromosome of D. melan- nant allele (Sfd/sfd) was female (berequisite genetic variation (i.e., ogaster, Chinicci (1971) found that cause males of this genotype were
genes that suppress recombination the recombination rate in this region remo ved from the breeding populaalong specific chromosomal regions) was reduced so that the map distance tion)' and an y fly homozygous for
is common in the gene pool.
became only 8.5 cM (although the the recessive aIIelomorph (sfd/sfd)
Although little is known about the physical distance of this region along was male (because females of this
molecular mechanisms that determine the chromosome remained the same). genotype were removed from the
the rate of recombination within local- Genetic analysis demonstrated that breeding population). This simple
ized chromosomal regions of meta- one or more genes on each of the selection protocol converted a popuzoans, genetic variation for localized major chromosomes contributed to lation with XY -male/XX-female
334
BioScience Vol. 46 No.5
chromosomal sex determination into
one with genic sex determination:
When sfd/sfd (males) are crossed
with Sfd/sfd (females), the progeny
retained to breed in the next generation are 1/2 sfd/sfd sons and 1/2
Sfd/sfd daughters.
To make a macroevolutionary
phenomenon (sexually antagonistic
allele accumulation near a new female-determining gene) occur on a
microcvolutionary time scale (i.e.,
within one National Science Foundation [NSF] grant period), the experiment was enhanced in two ways.
First, two Sfd genes on separate chromosomes were used simultaneously,
doubling experimental power because sexually antagonistic genes
could accumulate in two hot spots
simultaneously, instead of in just
one. Second, the two Sfd genes were
placed in the euchromatin near the
centromere, an area where genes are
approximately 7.5 times as dense
per map unit than at typical chromosomal locations. Consequently, ex perimental power was further increased by a factor of 7.5, so that the
accumulation of female-benefit sexually antagonistic genes in this 29generation experiment was comparable with what would be expected
in a 29 x 2 x 7.5 = 435-generation
experiment with a single gender-determining gene in a typical chromosomal region. In the replicated control populations, the same Sfd alleles
and protocols were used, but the
gender of the homozygotes and heterozygotes was switched for each
generation. In these controls, sexually antagonistic female -benefit alleles should not accumulate beyond
the normal level at a typical autosomal region.
After 29 generations the two chromosomal regions containing the new
female-determining alleles (and the
chromosomal regions tightly linked to
these alleles) were put into males, using
standard genetic crossing procedures,
and the lifetime fitness of these males
was measured. Fitness of males carrying the chromosomal regions adjacent
to the two Sfd alleles was reduced
by more than 50% relative to males
receiving the same regions from the
control populations. Most of the reduction in fitness was attributable to
mating performance rather than
survivorship. This result supports the
May 1996
Adults
Females
Males
Figure 3. Artificial selection protocol used to make an arbitrary dom inant allele (D)
on an autosome act as a synthetic female-determining allele (S(d). Heterozygous
females (Dd) are crossed to homozygous recessive males (dd) , producing both
homozygous and heterozygou s offspring. Only heterozygous daughters and homozygous sons are retained and bred each generation.
idea that sexually antagonistic alleles are common in the gene pool of
D. melanogaster and that a sex-determining G allele produces a hot
spot for the accumulation of sexually antagonistic alleles that are deleterious to the homogametic sex .
These experiments did not prove that
the genes responsible for reducing
male fitness accumulated because
they increased fitness in females . It
is possible, although less likely, that
these male-detriment genes accumulated via genetic drift or genetic
hitchhiking (see below) because of
their tight linkage to the femaledetermining genes. In either case,
these experiments confirmed that the
G allele produces a hot spot for the
accumulation of alleles deleterious
to the homogametic sex. Moreover,
the unexpectedly large magnitude of
the reduction in male fitness suggests that a major battle of the sexes
may be going on at the level of the
genome. Each sex may be restricted
in its adaptive evolution because
both sexes must share a common
gene pool and alleles beneficial to
one sex are sometimes maladaptive
to the other (or are tightly linked to
such genes) .
The two lines of research with
Drosophila (i.e., genetic variation
for sexually antagonistic genes and
localized suppression of recombination) provide direct experimental
evidence for the operation of the
genetic chain reaction lead ing to the
evolutionary elimination of recombination between the X and Y chromosomes. But what are the consequences of a lack of recombining on
the Y?
Theory for the degeneration of
a nonrecombining Y
Once the Y chromosome stops recombining with the X chromosome,
which continues to recombine in XX
females, it becomes a clonal (i.e.,
asexual) component in an otherwise
sexually recombining genome .
Nonrecombining Y-linked genes degenerate, whereas recombining Xlinked genes persist over geological
time. In an interesting parallel, it
335
has been repeatedly observed that
lineages of asexual multicellular
species are almost always short lived
on a geological time scale, whereas
lineages of their sexually recombining relatives persist (Bell 1982). Much
of the theory developed for the adaptive significance of recombination in
sexually recombining versus asexual
organisms can be applied to the X
and Y chromosomes. In both contexts, the major question is: Why
should the absence of recombination
ca use lineages of organisms (chromosomes) to go extinct (deteriorate)?
In the case of the Y chromosome,
degeneration via Muller's shelteredlethal model (Muller 1918, 1932)
was the first proposed explanation.
This model posits that because the Y
is permanently heterozygous, lossof-function mutations (which the
model assumes are completely recessive) on the Y chromosome would
virtually never be expressed. Hence,
natural selection would not prevent
loss-of-function mutations from accumulating and gradually leading
to deterioration of the Y.
However, Fisher's (1935) quantification of Muller's sheltered-lethal
model showed that in large populations, before the Y chromosome has
deteriorated, there are sufficient Xlinked loss-of-function mutations that
are allelic to those on the Y chromosome to prevent complete sheltering.
As a result, loss-of-function mutations
cannot accumulate on the Y chromosome. Studies at the whole organism
level by Kitagawa (1967) and others
(summarized in Simmons and Crow
1977) were even more damaging to
Muller's sheltered-lethal hypothesis
because they showed that so-called
recessive lethal mutations actually
reduce fitness by a small percentage
when heterozygous. Subcellular level
studies of enzyme flux rates and pool
sizes of intermediate substrates, carried out with heterozygotes for lossof-function alleles (reviewed in
Kaeser and Burns 1981), also indicate that sheltering is incomplete.
Lack of complete recessiveness is
likely to prevent loss-of-function alleles from accumulating on the Y
chromosome.
If sheltering ofY-linked mutations
cannot explain deterioration of the Y
chromosome, then why does it decay
once recombination is halted? Popu-
336
lation genetic theory predicts decay
via a variety of mechanisms, most of
which only operate in nonrecombining genomes or chromosomes.
These include sampling drift, genetic hitchhiking, background-trapping, Muller's ratchet, and mutational overload. These can be
descri bed most easily in their original context of a sexual species that
splits into sexual and asexual lineages, so I describe these decay
mechanisms in the more general context of asexual organisms.
The simplest form of decay is due
to sampling drift (random genetic
drift) and is expected to occur in both
sexual and asexual lineages. To understand this form of genetic decay,
consider a new deleterious mutation
in a finite diploid population of size
N. Natural selection is a deterministic process that acts to decrease the
frequency of the new mutation. Sampling error will randomly increase
or decrease its frequency each generation. When the change in frequency due to selection is small relative to that due to sampling error,
natural selection is overwhelmed by
sampling error, and the new deleterious mutation can become fixed in
the gene pool by chance accumulation.
Using diffusion analysis originally
developed in physics and chemistry,
population genetic theory (reviewed
in Crow and Kimura 1970; see Wright
1931 for an alternative approach)
predicts that deleterious mutations
will accumulate despite selection
whenever s < 1/(4N ), in which s is
the decrement to fitness associated with
a mutation in the homozygous state
and N; is the effective population size
(approximately equal to the number of
breeding adults in a population). Even
when the population is large, mutations of small effect (i.e., those with
small s values) are likely to accumulate, and therefore all finite populations are chronically decaying. Consequently, finite populations must
perpetually evolve to counter such
decay.
The other decay mechanisms operate only in asexual lineages and are a
consequence of variation in the genetic
background of mildly deleterious mutations (i.e., mutations reducing fitness by a few percent or less when in
the heterozygous state). Most new mu-
tations fall into this category (Crow
and Simmons 1983). To introduce these
additional decay mechanisms, consider the fate over thousands of generations of a hypothetical, new population founded by a single asexual
female-the progenitor. (Note that the
hypothetical bottlenecked population
is a simplification used to illustrate the
mechanisms by which asexual populations decay over time. The underlying
principles, however, are completely
general because all individuals in any
asexual population can trace their ancestry back to a single common ancestor or progenitor.)
We can describe the population at
any point in time by plotting the distribution of individuals carrying 0, 1,
2, ...,n mildly deleterious mutations.
Only mutations that are mildly deleterious in the heterozygous state (i.e.,
that reduce fitness by no more than a
few percent) are considered, because
natural selection rapidly removes all
mutations that are dominant and highly
deleterious. Because the population is
bottlenecked down to one individual,
the original population is composed
entirely of a single individual with P
deleterious mutations (P, which represents the progenitor class, is more than
because the original female was
unlikely to be mutation-free; Figure
4a).
In each subsequent generation, three
processes affect the distribution of
mutations per individual. First, mutation adds an average ofUD new mildly
deleterious mutations per genome (top
arrow, Figure 4b). Mutation studies on
multicellular organisms (reviewed in
Crow 1993) are still inconclusive but
indicate that UD is probably greater
than one per diploid genome, and
perhaps five or more. Mutation also
adds an average of UB new beneficial
mutations, although such mutations
appear to be rare (i.e., UB « U D ) .
Second, as new mutations begin to
accumulate and produce genetic variation' natural selection reduces the mean
number of deleterious mutations in
each generation because individuals
with fewer deleterious mutations tend
to produce more surviving offspring
(middle arrow, Figure 4b). Third, sampling error either increases or decreases
the number of individuals in each mutational class randomly (bottom,
double-headed arrow, Figure 4b).
Initially there is no variation in
°
BioScience Vol. 46 No.5
a
C
a tally for the P + 1 class in the next
gen eration (Figure 4d). Some of the
recruits to thi s class will be derived
Natur al selection
%
from progen y from the P class that
%
received one new mildly deleterious
Sampling drift
mutation, and the rest will be produced fr om the P + 1 cla ss itself.
oo' 0
p
o
Because at steady state th e number
Number of deleterious
Numberof deleterious
mutations
in the P + 1 class does not change
mutations
from generation to generation, the
P + 1 class is generated only in part
from its own reproduction , with the
remainder being genera ted from
mutated recruits from the P class.
More generally, all mutational
classes except the P class are not selfP
P+1
sustaining because some recruits in
Surviving Offspring
the next generation come from a
Number of deleterious
cascading down of newly mutated
mutations
offspring from less mutated classes
Figure 4. The distribution of mutational classes of a hypothetical pop ulation (Figure Sa).
founded by a single female. (a) The founding female has a genotype with P mildly
This simple characteristic of asexual
deleterious muta tion s (the progenitor class). (b) During each generation, mutation populations has an important implicaadds an average of U o new mildly deleterious mutation s (top arrow ). At the same tion: Barring new beneficial mutations,
time, selection removes such mutations (middle arrow ) and sampling error ran- individuals in all but the P class give
domly adds or removes them (botto m double-headed arrow ). Mutation also add s
beneficial mutations at a very low rate of UB « Uo' (c) Recurrent mutation and rise to lines of descent that are not selfselection ultimatel y lead to an equilibrium distribution of mutati ons per genome. sustaining and are th erefore declining
Sampling erro r chan ges the realized form of this distribution each generat ion in a toward eventual extinction. Only indistochastic fashion . When the genome-wide murat ion rat e (U Il ) is large, only a small vidu als in the P class produce lin es of
fraction of individual s remain in the progenitor class (P). (d) At equilibrium, only descent that persist over geological
the progenitor class is self-sustai ning becau se recruitment for the replacement of time . Because individuals flow unidirecall other classes (e.g., P + 1) is made up in part by newly mutated offsprin g derived tionall y from less to more mutated
from less mutated classes (stippled portion of P + 1 surviving offspring).
classes, the population is sa id to be
geneticall y polarized, which guarfitness, natural selection cannot op- into two unequ al parts: a tiny, self - antees that all individuals are ultierate, and deleterious mutations ac- perpetuating progenitor class, and mately derived from ancestors who
cumu late (Figure 4a) . As mutations what is essentiall y the living dead resided in the P class. An asexu al
accrue, heritable variation in fitness (i.e., the remaining majority of the population therefore can be d ichotoincreases, causing the strength of population, which produces lineages mized int o the progenitor (P) class
natural selec tion to continually that are doomed to eventual extinc- and the living dead (Figure Sa) .
build . Ultima tely, mutations stop tion).
To appreciate the significance of
accumulating when the strength of
To understand why asexual pop u- genetic polarization, first consider a
selection bui lds t o a point sufficient lations are genetically polarized, it new beneficial mutation with a minor
to offset recurrent mutation, and a is necessary to carry out some simple, effect on fitne ss (Figure 5b). Such a
characteristic equilibrium distribu- al beit tediou s, bookkeeping on the re- mutation has a high probability of bet ion is achieved (Figure 4c). The production of the P and P + 1 classes ing introduced into a genetic back exact shape of the steady-state distri- (Figure 4d) . Let N , and N p + ! be the ground carrying many mildly deleteribution of mutations va ries with the number of individuals in the P and ous mutation s. As a result, the
form of multilocus select io n, but P + 1 classes re spectively . To persist, beneficial mutation is trapped in a
unless UD is small, onl y a small the P class must produce more than genetic lineag e that is doom ed to
fract ion of individuals remain in the N , surviving offspring because some eventual ext inction, and it cannot
lea st mutated progenitor (P) class, (or most, when UD is large ) offspring persist in the population (background
a nd mo st individuals carry many are likel y to carry one or more new trapping; Manning and Thompson
mildly deleterious mutations .
mildly del eterious mutations. If we 1984, Peck 1994, Rice 198 7b ). To
When sexual recombination is ab- temporarily ignore new beneficial persist, the mutation mu st be introsent , the distribution of mutational mutations, all of the recruits to the P duced into the P class, a nd therefore
clas ses becomes genetically polar- class are derived so lely from the most beneficial mutations a re lost
ized . This polarization is respon- reproduction of thi s class (i.e., the P and progressive evolution is slowed
sible for all of the additional decay class is self- sustaining) .
considerably. In sexual populations,
processes that operate in asexual
The P + 1 cla ss and all other more background trapping is eliminate d
populations . In short, genetic polar- mutated classes are, however, not because recombination freely moves
ization splits an asexual population self-sustaining. To see why, consider new beneficial mutations among mu 100
May 1996
b
New mutations
100
337
a
eage. In this case, one or more mildly
deleterious mutations are likely to
" hitch a ride " with the new beneficial mutation as it accumulates in
the popu lation. Therefore, progres%
sive evolution at one locus is likely
to be at th e expense of the accumulation of one or more mildly deleterio
p'
o
p
ous m utations at other loci (genetic
Number of deleterious mutations
Number of deleterious mutations
hitch hiking decay; Manning and
c
Thompson 1984, Rice 1987b) .
d
%
When the expected number of individuals in the P class is small
(2)
(fewer than approximately 100 individuals; Maynard Smith 1978), then
1
there is a nontrivial probability that
all members of this class will fail to
z
leave descendants in any generation
(Charlesworth 1978, Haigh 1978). If
sexual recombination is present, the
%1_(4_)
eIC.
P class is rapid ly regenerated and
Surviving
p
offspring
p
Number01deleteriousmutations
the loss of the P class is inconsequential (Figure Sci. But with asexual
reproduction, reconstitution of the P
Figure 5. Genetic polarization and its consequences for the genetic decay of an class is expected to take many genasexual population. (a) Genetic polarization is the unidirectional flow of offspring erations, because it requires a new
from less to more mutated classes. As a consequence, only the progenitor class (P) beneficial mutation and DB is small.
does not depend on recruitment from less muta ted classes for part of its reproduc- In the interim, loss of the P class
tion. This dichotomizes the population into a small, self-sustaining progeni tor
weakens selection on the remaining
class, which gives rise to persistent lineages, and the non-self-sustaining living dead,
classes
so that the bal a nce between
from which all lineages are marching toward extinction. (b) Background trapping:
mutation
and selection will move
New beneficial mutations are inefficiently recruited into asexual pop ulations
because most (dotted arrows) are trapped in the extinction-bound lineages of the the distribution to the right (Haigh
living dead . Genetic hitchhiking occurs when a genome carrying a small number of 1978), making the P + 1 class the new
mildly deleterious mutations receives a beneficial mutation of large effect and progenitor class (Figure Sc-2) . To
thereby is converted into a new progenitor class (P'), with P' more than P. recover from this "turn of Muller's
Progressive evolution at one locus is therefore at the expense of mutation accumu - ratchet" (Felsenstein 1974, Muller
lation at one or more other loci. (c) Muller 's ratchet: (1) The P class is lost due to 1964) a reverse mutation, a compensampling error (arrow) . (2) Absence of the P class weakens selection on all satory mutation, or a new beneficial
remaining classes, which moves the mean of the distr ibution to the right . (3)
mutation must accumulate in the
Regeneration of the P class via progressive evolution (a reverse mutation, a
compensatory mutation, or an unrelated beneficial mutation) is slow due to population. Such progressive evo lubackground trapping, and in the interim the P + 1 class (best remaining class) is lost tion is slow due to background trap by sampling error (arrow) . (4) The best remaining class may be lost many times ping. Consequently, th e best remainbefore progressive evolution moves the distribution a single step back to the left. ing mutational class may be lost
This asymmetry leads to a net accumulation of mildly deleterious mutations. (d) many times due to sampling error
Mutational overload occurs in asexual organisms when the genome-wide mutation before the successful recruitment of
rate (Do) is high relative to the fecundity of the progenitor class (R o p or the per capita a single reverse, compensatory, or
net reproductive rate of the progenitor class). Model ing mutation as a Poisson new beneficial mutation. In this way,
process, only a fraction e -uo of offspring from the P class are unrnutared and remain mildly deleterious mutations graduin this class.
ally accumulate in an asexual lin eage due to samp ling error and getatio na l classes. Quantitative work organisms or chromosomes.
netic p ol ar iza ti on.
(Manning and Thompson 1984,Peck
Next, consider a beneficia l m uta tion
T he fina l decay mec hanism is mu1994) demonstra tes that background of large effect th at substantially in- tational overload (Figure Sd), which
trapping can substantially slow the creases fitness (Figure 5b). In this occurs when the progenitor class does
ra te of progressive evolution such situation, most beneficial mutations not produce enough unmutated surthat asexual populations recruit new are still likely to be lost due to viving offspring to replace itself. Per
beneficial mutations tens to thou- backgro und trapping, but new ben- capita lifetime reproduction is gensands of times slower than sexually eficial mutations trapped in m uta- erally expressed as the net reproducrecombining popu lations. In sum- tional classes neighboring the P class tive rate (R p)' and this value for the
mary, background trapping causes may cause the carrier individual to P class is denoted as R o p. If there
progressive evo lution to be far slower exceed the fitness of the P class and were no new mutations, Ro p must be
in asexual than sexual lineages of give rise to a new progenitor lin- 1.0 for the progenitor class to perProgenitor
class
I
Living dead
b
Progenitor Living dead
class
%
I
338
BioScience Vol. 46 No.5
sist. With R o P less than 1.0, a succes- some is also expected to accumulate
sion of new' progenitor classes will beneficial mutations more rapidly than
be lost recurrently. When new muta- the Y due to background trapping,
tions occur, R o p must be increased which over time causes Y -linked alleabove unity to accommodate the loss les to become relatively inferior.
of surviving, but newly mutated, offspring to more mutated classes.
Recent experiments on Y
If we model new mutations as a chromosome degeneration
Poisson process, then some simple
calculations demonstrate that a frac- We cannot hope to directly observe
tion (e- UD) of the surviving offspring the genetic decay of the Y chromoare likely to receive no new mildly some in nature owing to its slow
deleterious mutations. In this case, speed of operation. Two alternative
approaches are possible. One apRo,p must be more than or equal to
eUD for the progenitor class to persist. proach, taken by the Steinemanns
As U D increases, the requisite mini- and their collaborators, is to look for
mal number of surviving offspring the footprints of the decay process
(measured by RO,P(min) on a per capita via a molecular dissection of the Y
basis) increases exponentially. For chromosome in those species whose
example, if an average of five new Y chromosome is presently degenermildly deleterious mutations were ating. A second approach, used by
produced during the production of a my laboratory, uses population gediploid asexual egg, then RO,P(min) netic theory to solve for experimenwould be more than 148, which is tal conditions under which the Y
beyond the reproductive capacity of chromosome will genetically decay
many vertebrates. Asexual reproduc- so rapidly that degeneration can be
tion in such species would lead to observed directly in the la boratory
continual decay in the fitness of the on a microevolutionary time scale.
population and, eventually, to its
To create a synthetic Y chromoextinction. When sexual recombina- some whose decay could be meation occurs, however, the P class is sured directly, I used genetic markproduced not by its own reproduc- ers and artificial selection protocols
tion but via reassortment of muta- similar to those described a bove for
tions from the population as a whole. the sexually antagonistic genes exIn this case, epistatic selection and periments to endow ordinary autopositive assortative mating for fit- somes with the major characteristics
ness can greatl y reduce the requisite of the Y chromosome (i.e., they
net reproductive rate for the P class, lacked genetic recombination and
and its persistence is possible even were passed on exclusively from fawhen U D is large.
ther to son; Rice 1994). The experiThe importance of mutational ments were designed so that the
overload depends on the magnitude major mechanism by which the Y
of U D , which is determined primarily chromosome was expected to decay
by genome size of coding genes. was Muller's ratchet.
When the nonrecombining genome
Theory (Haigh 1978) indicated
(or genomic component) is small, as that the speed of the ratchet depends
in the case of bacteria, viruses, or on the generation time of the organsmall Y chromosomes, this decay ism, the chromosome-wide mutation
process is likely to be unimportant. rate to mildly deleterious mutations,
But when the nonrecombining ge- the effective population size (Ne ) ,
nome or genomic subunit is large, and the mean decrement to fitness of
mutational overload may be the pre- individual, mildly deleterious mutadominant decay process.
tions. The rate of decay increases
Summarizing with respect to the X with decreasing generation time and
and Y chromosomes, a recombining X effective population size and with
chromosome is expected to decay increasing mutation rate and mean
slowly due to sampling drift, but a clonal decrement of a mutation on fitness.
Y chromosome is expected to decay far
The generation time was made
more rapidly, due to the additional small by using the fast cycling speoperation of Muller's ratchet, genetic cies D. melanogaster, which has a
hitchhiking, and possibly mutational generation time of less than two
overload. In addition, the X chromo- weeks. I made the mutation rate of
May 1996
the synthetic Y chromosome high by
virtue of its large size; sex-specific
artificial selection on visible marker
genes was used so that both of the
major autosomes of D. melanogaster,
collectively containing 80% of the
genome, co segregated like a giant
nascent Y chromosome. Effective
population size was made small by
permitting only 32 synthetic Y chromosomes to be transmitted across
each generation. The mean effect of
a mildly deleterious mutation was
not experimentally manipulated, but
this value was presumed to be relatively small based on prior studies
(reviewed in Simmons and Crow
1977).
There were a total of five synthetic Y chromosome lines, each with
a paired control in which recombination was permitted and the autosomes were not restricted to males.
Computer simulations spanning the
range of likely values for the effects
of mildly deleterious mutations and
the chromosome-wide mutation rate
indicated that the above combination of parameter values should speed
the ratchet process to the point where
it could be observed directly over a
period of only one or two years and
that recombination should rescue the
controls from most of this decay.
Deterioration of the synthetic Y chromosome, and the recombining chromosomes in the controls, was assayed not by directly sequencing
specific genes (because thousands of
gene loci were contained on the synthetic Y chromosome, this approach
was not feasible) but by using genetic crosses to place the chromosomes into a standardized genetic
background and measuring fitness.
After only 35 generations, there
was a strong consensus among the
synthetic Y lines demonstrating statistically significant decay in fitness
relative to their recombining controls (p < 0.0006). This decay was
corroborated by a more extensive set
of fitness assays at generations 48,
49, and 50. 1 Such rapid decay in the
Y is not expected in natural populations, with their smaller Y chromosomes and larger population sizes;
nevertheless, these experiments demonstrate that decay occurs in response to lack of recombination. Fac-
-w.
R. Rice, 1994, unpublished data.
339
tor s other th an M uller's ratch et may
ha ve contributed to th e o bse rve d decay, but M uller's ratchet is likel y to
have been th e major co ntr ibuto r.
Molecular analysis of a
degenerating Y chromosome
The ex periments just descr ib ed demonstrate decay of a Y chro mos ome in
respo nse to th e lack of recombinaMale Y X.., Xnew
ti on, but th ey say nothing a bout th e
m ol ecula r mech ani sm s by w hic h
Figure 6. A schematic dra wing of th e sex
decay ac tua lly occ urs . This aspect of chro mosomes of Drosop hila m iranda.
Y chromoso me evo lution ha s been T he X XY/X XXX sex det erminati on sysaddressed by th e Ste ine ma nn gro up tem develop ed from an ances tra l XY/XX
(Steine ma nn 19 82, Ste ine mann and system du e to a fusio n (i.e., t ran slocaStein em ann 1990, 1991, 19 92, tion ) of one member of a hom olo gou s
Steinemann et al. 1993). Steinemann pair o f autoso mes to th e orig ina l Y ch roet a l. (1 99 3 ) used Dr osophila mosome, w hereas th e ot her hom ol omiranda as a model sys te m beca use go us a utoso me re mai ne d free . T he ex a recent (less th an 5 million yea rs tant Y ch ro moso me has an o ld sectio n
ago) tr an slocation fused o ne mem- (Yold)' co nsis ting of th e origina l Y chromosome, and a new section (Y ), con ber of a pai r of hom ol ogou s auto - tain in g the translocated a u tos;;'~e .
so mes onto thi s species' ex ist ing,
alrea dy degenerat ed Y ch romosome,
producin g an X o !dX new Yco mpos ite
. sex teri zed , th er e are approxima tely 5 0
chromosom e system (Figure 6). Dur- differ ent kinds of T E, with an av ering meiosis th e ori gin al portion of age of approximately 50 members of
the Y chro moso me (Yo!) pairs with each T E per genome (Lindsley and
the o rigina l X chro moso me (X old)' Zimm 1992 ). Insertion of a T E into a
while th e newl y acqui re d, previou sly new locati on frequentl y disrupts geautosom al portion of th e Y chromo- netic functio n in th e chromos oma l
so me (Y ) pair s w it h it s fr ee, region neighb oring th e inserti on site,
nontransl~~ated hom ol og (X ne) . Be- and an unu suall y high acc um ulation
cau se of t he tran slocation , a lar ge of T Es on a Y ch ro mosom e could
chro moso ma l seg me nt conta ining th erefor e potentiall y lead to its gethousand s of genes was introduced netic in acti vation.
onto th e Y a nd became a new,
Using in sit u hybridi zation technonrecombining differ ential segment niques (i.e., microscopic examina(bec au se th ere is no intrachrom- tion of ch romosomes ex pose d to ra osom al r ecombin at ion in m al e dioactively labeled pieces of DNA
D rosophila) . Becau se th e transloca- th at spec ifica lly attach to th e sites
tion is recent on a geo log ical time where ex ta nt T Es reside) to map th e
sca le, degen eration of Y
is ex- location of two fam ilies of T Es, it
pected to be presently oc2~Wrring at was fo und th at both T E t ypes had
hu nd red s of loci sim ulta neo us ly; accumu late d on Ynewto a far greate r
th er efore, a mol ecul ar ana lysis of degre e th an on the ot he r chromoth ese genes sho uld catc h the deterio- so mes . Each TE had a den sit y at
ration pro cess in pro gr ess.
least fivefold high er o n th e nonreThe Ste inemanns ' lab oratory has combining Y
as co mpare d with
focu sed on deterioration caused by the X new or c~~parabl e autosomal
tr ansposable elements (TEs ), which are regions of th e geno me .
small seque nces of DNA, man y of
In add iti on to th is wh ole chromo which sprea d lik e par asite s throu gh - so me app ro ach , Steine ma nn et a l.
out th e geno me via a uto no mo us rep- look ed in det ail at a sma ll clu st er of
licatio n and inse rt ion into new chro - genes on th e new X and Y chro mo mo som al lo cati on s. M o st TEs so mes (Xn.)Ynew-linked genes) th at
accu mulate to on ly a limited exte nt co de fo r a su bse t of th e larval cuticle
within th e genome . For exa mple, in pr otein s (LC P 1-4 genes). A comD. m elan ogast er, the Drosophila pa rison of hom olo gou s 7-ki lo base
species wh ose T Es ar e best ch arac- segments co nta ining either X new- or
340
Ynew-linked LCP genes revealed a
stri king di ffer ence in express ion of
th ese gen es. As pr ed ict ed from th e
chromoso me-wi de an al ysis, th e Y
seq uence (co nta ini ng th e LCP 1:'4'
genes) was ridd led with T Es that
were ab sent o n th e homologou s X link ed sequenc e. Hypothesizing th;t
th ese T Es may have silenced th e
Y -linke d a lleles, Steinema nn et a l.
e~~wmi ned th e ex p ress io n of th e X and Ynew-linke d genes and found th~t,
indee d, all of th e Ynew-linked a lleles
we re either untranslat ed (LCP-1,2,4 )
or we re translated at a low level
(LCP-3). By tr an sforming th e LCP-2
and LCP-3 genes from Y into D.
melano gast er, Steineman~~t al. further showed th at removal of th e TE s
from the up st ream regul at ory regions
of th e LCP genes rest or ed gene ex pr ession . Less direct evidence indica ted th at T Es ma y have played a
ro le in silencing th e ot her two LCP
genes. Ano ther Y-linked LCP gene
(LCP-5, located o uts ide th e stud ied
gene clu ster ) was fo und to be active
on Y .
In ne;ddition to th e X versus Y
difference in TE s, th e Y-link ed sequ ence s of th e LCP gen es were fo und
to hav e diverged from th eir hom ologo us X-linked seq uences, wit h three
o r mor e amino ac id substi tutio ns at
eac h locu s, ma ny of whic h wo uld
have alte re d th e charge, hydrophobicity, or pol arity of th e diverged
am ino acids (when still ex presse d on
Ynewl. Th e Ynew-linked LCP-4 gene
also had accumulated a fra meshift
mutation, and th e Y-link ed LCP-2
gene had lost its methionine tran siti onal sta rt site .
What do th ese results reveal a bo ut
th e mechan ism (s) by which th e Y chromosome degenerates? First, th ey indicate th at TEs may play an im po rtant
rolein its degeneration. But why sho uld
TEs be far mor e frequent on the Ychromoso mes ?W ha t is the fun cti on al significan ce of such a differ ence?
Selectively neutral T Es would be
expected to accumulate on th e Y chromosome for two reasons. First, consider
a TE that was neutr al because it inserted
into a region of no nfunctio nal DNA on
th e nonrecombin ing Y chromosome.
Lac k of reco mb ina tio n pr events un eq ua l hom ol ogous meiotic exc hange
(a pr ocess where by two chro moso mes
w ith a T E at th e sa me chro mosomal
site rec ombine in such a way th at
BioScience Vol. 46 No .5
one chromosome ends up with two
tandem copies of the TE and the
other with zero copies) from physically deleting TEs. This reduced removal rate alone could cause neutral TEs to accumulate on the Y
chromosome. Second, if TE-induced
loss-of-function mutations were completely recessive, they might also
accumulate on the Y chromosome
via Muller's sheltered-lethal model,
although the operation of this model
seems unlikely.
Non-neutral TEs would accumulate on a nonrecombining Y chromosome for three reasons. First, they
would accumulate because of mutation accumulation processes that operate only in the absence of recombination (Muller's ratchet, genetic
hitchhiking, and mutational overload). Second, TEs would accumulate because lack of recombination
will prevent ectopic exchange among
homologous TEs at different (nonhomologous) genomic locations (ectopic exchange model; reviewed in
Charlesworth et al. 1994). This model
is based on the theoretical result that
selection can stop the open-ended accumulation of parasitic TEs only when
the strength of selection increases in
a steeper-than-linear fashion as TEs
accumulate in the genome. The importance of ectopic exchange is that
it produces aneuploid gametes (i.e.,
gametes with unbalanced genomes
containing lethal deletions or duplications of a chromosomal region)
and is therefore thought to provide a
strong selection against the openended accumulation ofTEs (reviewed
in Charlesworth et al. 1994).
Third, and counterintuitively,
non-neutral TEs 'may accumulate
because of positive Darwinian selection. Silencing would be selectively
advantageous if the Y-linked genes
had diverged from their X-linked
alleles in a maladaptive way, either
by mildly deleterious mutations accumulating and/or by the X-linked
alleles evolving to a superior form
more rapidly than their Y-linked
homologs (due to background trapping on the Y chromosome). Either
way, once the Y chromosome becomes fixed for alleles that are sufficiently less fit than their X-linked
homologs (e.g., as might occur when
the gene product of the inferior Ylinked allele competes for substrate
May 1996
with the superior product from the
X-linked allele), there will be active
selection for any mutation that silences the Y-linked allele. TE insertion in the regulatory region of a
gene is a simple way to evolve an
inactive allele (or one with reduced
activity). Thus the TEs that have
accumulated on the Y chromosome
and inactivated two or perhaps all of
the Y-linked LCP genes may represent a case of natural selection turning off less fit Y-linked alleles.
Another large group of experimental studies has shed additional
light on the evolution of the Y chromosome. For more than a decade,
molecular biologists have raced to
identify and characterize the testisdetermining factor of mammals
(Tdf-studied primarily in humans,
mice, and several marsupials). Several candidate genes have been sequenced, and comparisons among mammalian species have provided
information on the rate of divergence among Y-linked genes (see, for
review, Hurst 1994, Wachtel 1994).
These sequencing studies have produced two key results. First, at least two
Y-linked genes (Sry [sex-determining region on the Y, now established
to beTdf] and ZfY[a Y-linkedzincfinger protein locus that codes for a
DNA-binding regulatory protein])
are evolving far more rapidly than
typical autosomal genes. Hurst
(1994) argues that selection, more
specifically intragenomic conflict
(i.e., antagonistic coevolution between two or more loci within the
genome of the same species), rather
than sampling drift or normal positive Darwinian selection, is driving
this fast pace of evolution of Ylinked genes.
Second, the sequencing studies demonstrate that the Y chromosome is continuing to degenerate, as evidenced by
certain Y-linked genes being nonfunctional in one species and functional in
another despite the small number of
functional genes remaining on the
mammalian Y chromosome (e.g., the Ylinked Sts [steroid sulfatase] gene is
functional in mice, whereas it is a nonfunctional pseudogene in humans). The
significance of this observation is that
Muller's ratchet operates slowly if at all
when the chromosome-wide mutation
rate to mildly deleterious mutations
is small, as it would be when few
functional genes remain on the Y. So
the observed continued decay of the
Y even when it is almost completely
degenerated suggests the operation
of some other decay process, possibly genetic hitchhiking, active selection to silence inferior Y-linked alleles, or intragenomic conflict.
Clonal chromosomes versus
clonal genomes
Although an understanding of how
the Y chromosome evolves from an
ordinary autosome is interesting in
the context of chromosome evolution, it also has more widespread
application as a model system for
the study of the adaptive significance of sexual recombination. Phylogenetic studies indicate that most
asexual lineages ultimately go extinct while their sexual relatives persist (Bell 1982). Similarly, once the
Y chromosome stops recombining
with the X chromosome it also becomes doomed to extinction (i.e.,
all, or virtually all, genetic activity
is eliminated). The similar fates of
clonally propagated species and
chromosomes suggests that sexual
recombination is a prerequisite for
persistence over long periods of evolutionary time.
Many hypotheses have been put forward for the adaptive significance of
recombination (see,for review, Michod
and Levin 1988). The fact that nonrecombining chromosomes as well as organisms are doomed to extinction suggests that any general theory for the
adaptive significance of sex should
apply to both of these entities. Therefore, many of the ecological hypotheses for the adaptive significance of
sex, such as parasite-host coevolution
(Jainike 1978, Levin 1975) or resource
partitioning among siblings (Williams
1975), are unlikely to be complete
explanations for the adaptive significance of sex because they do not
explain the extinction of nonrecombining chromosomes.
There are, however, important differences between clonally propagated
Y chromosomes and species. First, the
Y chromosome is permanently heterozygous, with redundant, homologous genes being present on the X chromosome. This genetic redundancy may
reduce the fitness consequences of new
deleterious mutations on the Y chro341
mosome, and hence speed genetic
decay, because partially recessive
deleterious mutations rarely become
homozygous. This difference between nonrecombining Y chromosomes and the genomes of organisms
applies only to haploid and not diploid asexual organisms.
Second, as loss-of-function genes
accumulate on the Y chromosome,
the evolution of dosage compensation counterbalances the gene product imbalance that would otherwise
arise. Dosage compensation ameliorates the deleterious effects of degeneration of the Y chromosome, which
should permit it to degenerate faster
than genes in an asexual organism
(Charlesworth 1978). Nonetheless,
Y chromosomes have degenerated in
groups like birds, in which dosage
compensation has not been observed.
The impact of genetic redundancy
and dosage compensation on genetic
decay can be measured directly in diploid organisms, such as D. melanogaster, that have a nonrecombining
autosome. For example, comparison can
be made with the small, nonrecombining so-called dot autosome (chromosome 4) of D. melanogaster,
which is not permanently heterozygous or dosage compensated. Interestingly, chromosome 4 has maintained substantial genetic activity
for millions of years, although there
is indirect evidence that it may be
decaying (Hochman 1976). Until
more detailed molecular work is done
on chromosome 4, however, we will
not know the full extent of its deterioration.
The third major difference between an asexual multicellular species and a Y chromosome is that the
genome-wide deleterious mutation
rate of a whole organism's genome
is far larger than the chromosomewide rate of the Y chromosome. It is
the genome- or chromosome-wide
mutation rate, not the per-nucleotide
rate, that determines the susceptibility of an asexual genome to the
additional decay mechanisms (Muller's
ratchet, genetic hitchhiking, and mutational overload) that operate only in
nonrecombining genomes or genome
segments. Consequently, the relative importance of the various decay
agents may differ between the two.
Despite the unique properties of
the Y chromosome, it constitutes a
342
simple and experimentally tractable
model system for deciphering the
adaptive significance of sexual recombination. The experiments with
the Y chromosome have focused on
the qualitative question concerning
the importance of the presence or
absence of recombination. To make
further progress we need to address
the quantitative question of the adaptive significance of varying levels of
recombination. In this context future
progress will likely be achieved by
experiments using different autosomal regions that have varying levels
of recombination.
Acknowledgments
I thank Suzanne Kohin and Brett Holland for comments on the original manuscript. My research was supported by
NSF grants BSR-8996268, DEB9118893, and DEG-9307735.
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