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Mutations from Venus, mutations from Mars
Date:7/28/2014

Some 15% of adults suffer from fertility problems, many of these due to genetic factors. This is something of a paradox: We might expect such genes, which reduce an individual's ability to reproduce, to disappear from the population. Research at the Weizmann Institute of Science that recently appeared in Nature Communications may now have solved this riddle. Not only can it explain the high rates of male fertility problems, it may open new avenues in understanding the causes of genetic diseases and their treatment.

Various theories explain the survival of harmful mutations: A gene that today causes obesity, for example may have once granted an evolutionary advantage; or a disease-causing gene may persist because it is passed on in a small, relatively isolated population.

Dr. Moran Gershoni, a postdoctoral fellow in the group of Prof. Shmuel Pietrokovski of the Molecular Genetics Department, decided to investigate another approach one based on differences between males and females. Although males and females carry nearly identical sets of genes, many are activated differently in each sex. So natural selection works differently on the same genes in males and females.

Take, for example, a mutation that impairs breast milk. It will undergo negative selection only in women. Conversely, a hypothetical gene variant that benefits women but is harmful to men could spread in a population, as it undergoes positive selection in half that population. Gershoni and Pietrokovski created a mathematical model for harmful mutations that affect only half the population; their model showed that these mutations should occur twice as often as those that affect males and females equally.

To test the model, the researchers searched in a computational analysis of the activities of all the human genes that appear in public databases, identifying 95 genes that are exclusively active in the testes. Most of these genes are vital for procreat
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Contact: Yivsam Azgad
news@weizmann.ac.il
972-893-43856
Weizmann Institute of Science
Source:Eurekalert

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