April 17, 2009 — First evolutionary study of X chromosome shows how X compensates for degeneration of Y
Berkeley — Move over, Y chromosome — it’s time X got some attention.
In the first evolutionary study of the chromosome associated with being
female, University of California, Berkeley, biologist Doris Bachtrog
and her colleagues show that the history of the X chromosome is every
bit as interesting as the much-studied, male-determining Y chromosome,
and offers important clues to the origins and benefits of sexual
"Contrary to the traditional view of being a
passive player, the X chromosome has a very active role in the
evolutionary process of sex chromosome differentiation," said Bachtrog,
an assistant professor of integrative biology and a member of UC
Berkeley’s Center for Theoretical Evolutionary Genomics.
UC Berkeley post-doctoral fellow Jeffrey D. Jensen and former UC San
Diego post-doc Zhi Zhang, now at the University of Munich, detail their
findings in this week’s edition of the open-access journal PLoS Biology.
our manuscript, we demonstrate for the first time the flip side of the
sex chromosome evolution puzzle: The X chromosome undergoes periods of
intense adaptation in the evolutionary process of creating new sections
of the genome that govern sexual differentiation in many species,
including our own," she said.
Not all animals and plants employ
genes to determine if an embryo becomes male or female. Many reptiles,
for example, rely on environmental cues such as temperature to specify
male or female.
But in life forms that do set aside a pair of
chromosomes to specify sex — from fruit flies to mammals and some
plants — the two X chromosomes inherited by females look nearly
identical to the other non-sex chromosomes, so-called autosomes,
Bachtrog said. The Y chromosome, however, which is inherited by males
in concert with one X chromosome, is a withered version of the X,
having lost many genes since it stopped recombining with the X
In mammals, that probably took place about 150
million years ago, while in the fruit fly Drosophila melanogaster, a
laboratory favorite, the sex chromosomes arose independently about 100
million years ago. In both humans and fruit flies, the Y chromosome has
dwindled from a few thousand genes to a few dozen.
intense interest in why and how the Y chromosome lost genes once it
stopped interacting with the X. Scientists have found that, as the only
chromosome pair that doesn’t break and recombine every time a cell
divides, the XY pair in males is unable to take advantage of the main
way deleterious genetic mutations are eliminated. The XX pair in
females does recombine, but for the Y, the only way to get rid of a bad
mutation in a gene is to inactivate or delete the entire gene. Over
millions of years, inactive genes are lost, and the Y shrinks.
you have no recombination, natural selection is less effective at
removing detrimental genes," said Bachtrog. "Y is an asexual
chromosome, and it pays a price for that: It keeps losing genes."
whose career has revolved mostly around the study of the degeneration
of the Y chromosome, decided to focus on the X chromosome several years
ago and went about searching for sex chromosome pairs that have arisen
more recently — and thus might be in the process of adapting to their
new role. Her paper centers around study of the three sex chromosomes
in a rare western fruit fly, Drosophila miranda, a darker-colored
cousin of D. melanogaster. (Many creatures have more than one pair of
sex chromosomes; the platypus, for example, has five pairs, all
While one of D. miranda’s sex chromosomes
is descended from the original sex chromosome that appeared in
Drosophila nearly 100 million years ago, a second originated perhaps 10
million years ago, and the third about a million years ago. The older
two look much alike, Bachtrog said: The Y chromosome in each pair has
lost genes to become a shadow of its former self, while the two X
chromosomes are indistinguishable from each other.
The third and
youngest sex chromosome is different. The Y is not yet shriveled,
though it contains many non-functional genes — about half the total —
that will eventually be lost. The X, which is dubbed neo-X, is
undergoing rapid change, however, with about 10 times the normal amount
of adaptation seen in the autosomes, according to the researchers.
adaptation, Bachtrog means that the gene sequences in the X chromosome
are becoming fixed as random mutations have finally settled on a few
beneficial changes that accommodate the increasingly irrelevant Y
chromosome. Between 10 and 15 percent of neo-X genes show adaptation,
compared to only 1-3 percent of autosome genes.
that is not surprising," Bachtrog said. "Neo-X is facing a much more
challenging situation than the autosomes because its pair, the Y
chromosome, is degenerating. Its genes are no longer producing
proteins, so neo-X has to compensate by up-regulating its genes. We
find a lot of genes on the X chromosome are involved in dosage
In humans, for example, all genes on the X
chromosome are twice as active to account for the lack of genes on the
Y. Women accommodate this by inactivating one entire X chromosome so as
not to produce too much protein, Bachtrog said.
in neo-X that Bachtrog suspects is taking place is the elimination of
genes that are harmful to females. Biologists have realized recently
that some genes have opposite effects in males and females, and
evolution is a tug of war between males jettisoning genes that they
find detrimental only to have females put them back, and vice versa.
good place to put sexually antagonistic genes that are beneficial to
one sex but detrimental to the other is on the sex chromosomes," she
said. The Y always ends up in the male, she said, so genes on the Y
chromosome won’t affect females.
"Conversely, the X chromosome
becomes feminized with genes that are good for the female but
detrimental to the male," said Bachtrog, adding that the X also becomes
demasculinized, losing genes that are of use only in the male.
search of more insights into the evolution of the X chromosome,
Bachtrog said she is looking for fruit fly species with older and
younger sex chromosomes "to study sex chromosome evolution in action."
She said evidence suggests that adaptation to being a sex chromosome is
most intense between 1 and 10 million years after it starts. Bachtrog
also is completing assembly of the genome sequence for D. miranda,
which is not among the 12 species of Drosophila currently targeted by
the genome sequencing community. She hopes that the fly will become a
model system like D. melanogaster.
"Now, finally, we are within
reach of studying model systems like D. miranda that we couldn’t think
of several years ago," she said, predicting that "whole genome
comparisons will revolutionize evolutionary biology, ecology and many
Source : University of California – Berkeley