Fungi and animals, including humans, have a lot in common

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News-Medical.Net Sex genes of infectious fungus closely resemble

human Y chromosome

Posted By: News-Medical in Medical Science News

Published: Wednesday, 10-Nov-2004

http://www.news-medical.net/?id=6232

Fungi and animals, including humans, have a lot in common when it

comes to the arrangement of genes that determine their sex,

according to new work by Medical Institute geneticists

at the Duke University Medical Center.

Regions of the genome that determine the sexual identity of the

infectious fungus Cryptococcus neoformans bear striking similarities

to the human Y chromosome -- the sex chromosome associated with male

characteristics -- the team found. The researchers reported their

findings in the December 2004 issue of the Public Library of Science

Biology (now available online).

The result suggests that, despite their differences, similar

evolutionary processes shaped the chromosomal sex-determining

regions in both groups, said HHMI investigator ph Heitman, M.D.,

director of Duke's Center for Microbial Pathogenesis. The fungus

might therefore serve as a useful model system for the study of sex

chromosome evolution and the genetic changes that can lead to

infertility, he said.

" The revolution in genome sciences has rapidly accelerated our

ability to elucidate the process by which sex chromosomes evolved, "

Heitman said. " While mechanisms of sex determination are extremely

diverse, our study highlights remarkable similarities among them in

widely divergent groups. "

The findings might also provide new insight into the process whereby

the infectious fungus spurs disease, because evidence suggests a

close tie between the genes involved in sexual identity and

virulence, Heitman added. The work was supported by the National

Institute of Allergy and Infectious Diseases.

Sexual identity is governed by sex chromosomes in plants and

animals. In humans and other mammals, males have one X and one Y

chromosome, while females have a pair of X's.

In fungi, sexual identity is determined by so-called " mating type

loci, " genes located in a contiguous region of the genome, but which

typically do not span an entire chromosome. C. neoformans exists in

two mating types determined by a single genetic locus. Earlier work

found that this sex-determining region is unusually large in C.

neoformans compared to other fungi, containing a series of more than

20 genes.

The researchers reconstructed the sequential evolutionary events

that fashioned the sex-determining region of the C. neoformans

genome by comparing it to that region in the related pathogenic

fungal species, Cryptococcus grubii and Cryptococcus gattii.

The sex-determining genome region appears to have acquired genes in

four main steps -- beginning with the acquisition of genes into two

separate sex-determining regions that later fused, the team

reported. Furthermore, they found that the fungal sex-determining

genes exist in clusters of functionally related genes. For example,

genes involved in mate recognition occur in tandem, as do those that

govern spore production.

Other researchers have found that the human Y chromosome -- and the

functionally-related gene clusters it contains -- has a similar

history, characterized by the " sequential capture of genes " on four

separate occasions, Heitman said.

The fungal mating type locus later underwent processes that suppress

recombination, they found. Recombination is the process whereby each

member of a pair of chromosomes exchange segments of DNA. The

procedure allows for new gene combinations to form and for the

repair of damaged DNA.

The human Y chromosome is also barred from recombination along most

of its length, a necessary requirement to prevent genes that encode

male traits from infiltrating the female X chromosome, Heitman

noted.

The researchers suggest that, despite the lack of recombination,

some fungal mating type gene repair might occur through the exchange

of gene segments within chromosomes. Certain sex-determination genes

occur in palindromic orientations –- head-to-head or tail-to-tail

repeats of particular sequences –- which would make such intra-

chromosomal repair possible, a pattern also found on the human Y

chromosome, according to Heitman.

" These similarities suggest that further study of C. neoformans

might help elucidate the genetic changes that can lead to

infertility in fungi and humans, as well as the repair mechanisms

that prevent its more common occurrence, " Heitman said.

Their findings might also yield insight into the mechanism whereby

C. neoformans invades the central nervous system to cause disease,

most commonly in patients who lack a functioning immune system, such

as organ transplant recipients and those with HIV/AIDS, Heitman

added. A single fungal mating type spurs the vast majority of all C.

neoformans infections, he explained, suggesting that sex

determination and virulence are closely linked.

Collaborators on the study include Fraser, Diezmann,

Subaran, Andria , Klaus Lengeler and Fred Dietrich, Ph.D.,

all of Duke.

http://www.dukemednews.org