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Is there a 'mother's curse' ?
The "curse" exists because there are two independent sources of genetic information within our bodies. One is the genome, all eukaryotes — eukaryotic cells are plant and animal cells surrounded by a membrane — have the largest portion of genes in the nucleus of each cell. However, a much smaller gene legacy is located in our mitochondria — small, bean shaped structures processing oxygen into energy; the only places in the cell where oxygen is reduced and eventually broken down into water.
Thus, mitochondria can be found in every area of the body with an intense need for oxygen — such as in all muscle tissues, including our heart. According to John Allen, a biologist at University College London not involved in this study: “...that’s a very fundamental feedback mechanism.” Mitochondria produce proteins right where they’re needed which better regulates energy production. Although other cell structures could benefit from this type of local control, only mitochondria have their own command center.
Now, a team of biologists at Vanderbilt University and the Fred Hutchinson Cancer Research Center in Seattle, have discovered mutant mtDNA in the fruit fly Drosophila melanogaster supporting the mother's curse theory in all animals.
Explains Maulik Patel PhD, assistant professor of biological sciences at Vanderbilt, and head of the study: "In the 20 years since this possibility was recognized, a few mitochondrial mutants have been reported that have deleterious effects on male offspring. But, none convincingly showed the mutation negatively affecting females. Our study is the first to look comprehensively for the effects of male-harming mtDNA mutants on females. We were fortunate to find one mutation that has a negative impact on male offspring without having any adverse affects on female siblings."
The "mothers curse" is one of the more bizarre consequences of natural selection. According to evolutionary theory, mitochondrial DNA (mtDNA) and nuclear DNA are locked in an unending competition. As one accumulates beneficial mutations, then the other is forced to adapt. This is known as the "Red Queen hypothesis," taken from "Through the Looking Glass" written by Lewis Carroll and spoken by the Red Queen: "...it takes all the running you can do, to keep in the same place."
Plants have much larger mitochondrial genomes containing larger numbers of genes. In plants, striking instances of male-harming mitochondria already have been discovered. As the mitochondrial genome in animals is much smaller, it makes it much harder to detect similar male-harming mutations.
The experiment that ultimately discovered male-harming mtDNA mutations took more than four years to complete. Scientists set up 18 independent lines of fruit flies, each with 300 females and 100 males. In 12 of these lines, virgin females were collected in each generation and mated with males from the original stock. Researchers did this for 35 generations (or 70 weeks). In the remaining six lines, females were allowed to mate with sibling males of their choice. Throughout this time, researchers monitored individual fly fitness to determine whether males were in someway harmed. When they were done, Patel along with Miriyala and Littleton (research technicians at the Hutchinson Center) found that a single-point mtDNA mutant had taken over only one of the fruit fly lines.
"We weren't looking specifically for mutations that affect fertility, but, in retrospect, it makes sense.
Their findings explain the relationship between mutant human mtDNA and slow sperm motility in 7 to 10 percent of men — mtDNA mutations may significantly be contributing to male sub-fertility.
Turning up cage temperature by four degrees Celsius caused male mice carrying the mutation to become almost completely sterile. This allowed the scientists to test a second prediction of the mother's curse hypothesis: the nuclear genome can evolve mechanisms suppressing male-harming mtDNA mutations and restore male fitness.
They mated females with mutant mtDNA to males from different fruit fly strains collected from around the world. Then they assayed the male offspring's fertility and were surprised to discover that nuclear genomes from many of these strains had completely restored male fertility.
In addition to Patel, Miriyala and Littleton, co-authors of paper include Janet Young from the Fred Hutchinson Cancer Research Center, Hieko Yang andYukiko Yamashita from the University of Michigan, Kien Trinh, Scott Kennedyand Leo Pallanck from the University of Washington. The research was conducted in the laboratory of evolutionary biologist Harmit Singh Malik at the Fred Hutchinson Cancer Research Center.
The research was supported by grants from the Helen Hay Whitney Foundation, the Mathers Foundation and National Institute of Health grants F30 AG045021, GM104990 and GM074108.
Mitochondrial DNA damage (RIGHT).
Image Credit: Global Research