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Why is the Y chromosome, which determines male development, slowly disappearing in human DNA? Fungal Model to Shed New Light on Human DNA

 Fungal Model to Shed New Light on Human DNA

The National Institutes of Health has awarded Professor Michael Hood a $444,651 grant to investigate the problem of chromosome degeneration.

This graphic, provided by Professor Hood, features a plot of mating type chromosomes of the fungus. As he notes, “Anther-smut fungus in the flowers of wild carnations serves as a model for the evolutionary genomics of sexual compatibility.”


Why is the Y chromosome, which determines male development, slowly disappearing in human DNA?


It’s a question that has baffled scientists since they began understanding DNA, and is one that Michael E. Hood, associate professor of biology, believes he can help answer—using a violet fungus that infects a tiny carnation-like flower.


The problem lies in the unusual nature of the human male sex chromosomes, the only two on the long string of human DNA that are unequally matched, with an X and Y pairing up to create a male. In all other chromosomes, humans have two copies, but that’s not true for the Y, which is always paired with an X.


This unusual combination means that changes to the Y chromosome are sheltered by its X counterpart; they never appear either as expressed mutations or get corrected, as similar changes would in other parts of the DNA sequence. It’s the evolutionary equivalent of a stalagmite in a cave, slowly building up defects one tiny change at a time.


“There seem to be certain places in the genome where harmful mutations accumulate,” Hood said. “The X can’t degenerate in that way because in females, that’s all you’ve got.”


While no one is really worried about men going extinct (as the tabloid interpretation would have readers believe), scientists are interested in understanding the gradual process of genetic deterioration and where it might eventually lead.


It’s a difficult question to explore since the answer involves tracking human DNA and the harmful mutations genomes accumulate over long periods of time. 


By using the anther smut fungus as a working model, and a rapidly evolving one at that, Hood believes he can offer key insights into genome function. The National Institutes of Health agrees: It recently awarded Hood a $444,651 grant through its Genes, Genomes and Genetics program to investigate the issue using the fungus.


There is no such thing as a male or female anther smut, but the fungi do have two mating types with a pair of chromosomes (remarkably similar to XY) that are undergoing degeneration in the same way.


There are other advantages to anther smut as well: the fungal models are safe for researchers to use, the fungus is easy to grow and, unlike humans, fungi have small genomes that make the sequencing process simple. Hood can not only grow a generation in a few weeks, but has access to a large group of related species, which gives him more information about the fungi’s evolutionary relationships.


This is not the first time Hood has used anther smut to test theoretical problems. In the fall, he was awarded a joint $1.7 million grant, together with the University of California Berkley and the University of Virginia, to use the fungus in the study of sexually transmitted diseases.


“Computer simulations, theoretical work, are really good at indicating what might happen in nature, but that’s quite different from saying what does happen in nature,” Hood said. “The empirical evidence, with a real biological system, finishes off that investigation in a way. 


By tackling fundamental questions—does the degeneration of the Y chromosome slow over time, for example, or does it simply continue until the chromosome is gone—Hood hopes that his work will eventually help clear the way toward solving basic problems humans face at the genetic level and in disease.


“One of the things I like most about biology is that there’s an answer in there somewhere and it takes real investigation in order to pull out the explanation,” Hood said. “It’s fun to do the work to try to resolve a mystery.”


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