Through their study of how selfish genes on the X and Y chromosomes compete, the Mueller Lab discovered that the loss of X-linked selfish genes results in male infertility.

One of the ways the X and Y chromosomes compete is that the proteins the genes encode are rapidly evolving and compete for the same protein substrate. The Mueller Lab is currently experimenting with mutating the proteins to identify advantageous mutations that enhance their binding capabilities to give them a competitive edge. These experiments are conducted in a yeast-two-hybrid system, where mouse genes are introduced into yeast. This research may have implications for understanding human male infertility, why some couples have more boys or girls, and speciation.

Meet Jacob Mueller

Jacob Mueller, PhD, is Associate Professor of Human Genetics at University of Michigan Medical School.

 

Selfish Genes

Mendel’s law of inheritance states that there is a 50-50 chance of passing to the next generation one of the two gene pairs you inherited from your mother or father. Selfish genes break this rule. 

Dr. Mueller and his team research selfish genes that influence the success of sperm to fertilize an egg.

Fertility

The discoveries made in Dr. Mueller’s lab can help researchers understand infertility and give us snapshots of genetic battles throughout evolution.

 

Microscopy

Microscopy plays a large role in the Mueller Lab’s work. Under powerful microscopes, they can see where proteins localize in sperm cells, or study the shapes of developing mouse sperm cells. 

Eden Dulka is a Post-doctoral fellow in the Mueller Lab.

 

Palindromes

A palindrome is a letter sequence that reads the same backward or forward, like “HANNAH.” Palindromic DNA sequences likely signal the presence of selfish genes. Researchers can study selfish genes through evolutionary time by meticulously searching for palindromic sequences across different species. 

Ann Marie Lawson is a Genetics and Genomics PhD student in the Mueller Lab.

Competition

Genes on the X and Y chromosome compete to attach to specific protein substrates. The Mueller Lab mutates individual protein positions to see which will bind the most effectively, allowing it to outcompete the others. They test these predictions by putting mouse genes in yeast to more effectively test many mutations simultaneously.

Martin Arlt is an Associate Research Scientist in Human Genetics, and part of the Mueller Lab.

 

Poison

One genetic innovation can be seen in the
t-haplotype chromosome in mice sperm. The
t-haplotype poisons the wild types, or naturally occurring chromosomes, so that it can be successfully transmitted. The poison decreases sperm motility– its ability to move– decreasing the likelihood of the sperm reaching an egg.

Callie Swanepoelis a Genetics and Genomics PhD student in the Mueller Lab.

 

 

 

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