By Marissa SteplerCommonly known as the “powerhouses” of the cell, mitochondria provide the vast majority of energy required for cells to function, grow, move, and thrive. Mitochondria self-replicate and have their own DNA, but only 37 of the approximately 3000 genes needed for mitochondrial function are found in mitochondrial DNA. The majority of genes contributing to mitochondrial energy generation, nucleotide synthesis, hormone production, and the many other functions of the mitochondria are located in the nuclear chromosomal DNA of each cell.
When the “powerhouses” of the cell fail, cellular health and function can be drastically decreased, often leading to cell dysfunction and death across numerous different cell types and tissues. In mitochondrial disease, this dysfunction occurs due to inherited or spontaneous mutations in nuclear genes encoding proteins involved in mitochondrial function or mitochondrial DNA. Mutations in nuclear genes can be inherited from either parent. However, because, in a fertilized embryo, all cytoplasm and mitochondria are provided by the egg, mutations in the mitochondrial DNA of a child are inherited solely from his mother. Furthermore, a mother’s mitochondrial DNA mutation may occur in a small enough percentage of her total mitochondria that she remains unaffected, yet the mutation may be lethal when passed on to her children. So if a mother knows she carries a mitochondrial DNA mutation, how can she prevent the transmission of the mutation to her children? Recently, researchers have addressed this problem through a new variation on in vitro fertilization (IVF) called three-parent IVF. In this procedure, instead of using an egg from a single female donor and sperm from a single male donor, eggs from two female donors – one from the mother and one from a female donor lacking mitochondrial DNA mutations – are used. When a cell, such as an egg cell, undergoes DNA replication, the dividing chromosomes are pulled apart by microtubule spindles before being separated into two daughter nuclei. In three-parent IVF, a technique called spindle transfer is used to extract the spindles and their attached chromosomes, which are then injected into the healthy donor egg from which the spindles have been removed. This new combined egg is then fertilized with the father’s sperm, resulting in an embryo which has maternal and parental nuclear DNA but healthy donor mitochondrial DNA. While this IVF method has been previously tested in primates and mammals, it was not attempted in humans until recently, when the procedure was used by a mother who had a mitochondrial gene mutation which results in Leigh syndrome, a lethal neurological disorder. After two of her previous children inherited the disease, the mother underwent spindle transfer three-parent IVF, which resulted in a successful pregnancy and birth of a healthy baby boy. Although considered controversial in some circles, three-parent IVF seems to be a powerful and effective method for preventing some inherited human mitochondrial diseases. As technology continues to advance, this procedure may be used to prevent other inherited disorders related to mitochondria and organelle dysfunction. Currently, this breakthrough procedure offers hope for parents carrying mutations in mitochondrial disease-related genes and for scientists researching organelle-related diseases. Sources: [1] https://www.sciencenews.org/article/three-parent-babies-explained [2]http://www.umdf.org/site/c.8qKOJ0MvF7LUG/b.7934627/k.3711/What_is_Mitochondrial_Disease.htm [3]http://whut.pbslearningmedia.org/resource/tdc02.sci.life.cell.mitochondria/the-powerhouse-of-the-cell/
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by Angela WongRecent discoveries may help shed light on what makes us all unique, and why even identical twins can be so unlike (Salk, 2016). These findings have large implications on not only what distinguishes us from one another, but also on what sets Homo sapiens apart from other eukaryotes. In a sense, these factors simultaneously define and unite us. LINE-1 retrotransposons (L1s), also called “jumping genes,” are small pieces of DNA that have been known to insert genetic information throughout the genome. “Jumping” around the genome, they amplify themselves which lead regulatory DNA to be copied and shuffled (Ivancevic, Kortschak, Bertozzi et al., 2016). Present in most healthy neurons, L1s are a source of genomic diversity on the brain. Variations between neurons within the same brain suggest that they “function slightly differently from each other,” says the study’s senior investigator, Rusty Gage. Due to L1s and other factors, each neuron contains around 1,500 unique mutations (Yong, 2015). Diversity of neurons, which process and transmit information in the brain, impacts one’s brain functionality (Salk, 2016). Additionally, at least a third of the 20,000 different genes in the human genome are expressed in the brain—the highest proportion of genes expressed in the human body. According to latest studies, L1s can also remove large chunks of DNA, affecting the genome even more significantly than previously thought. Evidence has shown that neurons from those with schizophrenia and Rett syndrome have above-average levels of L1 variations within their genomes. Researchers at the Salk Institute believe that these findings indicate will further the understanding of the role, and they plan to continue exploring the role of L1 variations and how they impact both brain function and illness (Salk, 2016). Other scientists conducted a “comprehensive phylogenetic analysis of elements from over 500 species from widely divergent branches in the tree of life” to examine the diversity of L1s, which are thought of as “tightly constrained, homologous, and ubiquitous elements with well-characterized domain organization.” They found that in recent times, the growth of L1 elements in mammalian species have diverged from lineages in other plants and metazoans, animals with cell differentiation. Illustrating that “both long-term inherited evolutionary patterns and random bursts of activity in individual species can significantly alter genomes” (Ivancevic et al., 2016). These two studies highlight the significance of L1s in the expression of characteristics that make each one of us unique, as well as uniquely human. Sources: Ivancevic, A. M., Kortschak, D., Bertozzi, T., & Adelson, D. (2016, September 26). LINEs between species: Evolutionary dynamics of LINE-1 retrotransposons across the eukaryotic tree of life. Genome Biology and Evolution. Retrieved from http://gbe.oxfordjournals.org/content/early/2016/09/30/gbe.evw243.abstract The brain’s stunning genomic diversity revealed - Salk ... (2016, September 9). Retrieved October 21, 2016, from http://www.salk.edu/news-release/brains-stunning-genomic-diversity-revealed/ Yong, E. (2016, October 1). The Surprising Genealogy of Your Brain - The Atlantic. Retrieved October 21, 2016, from http://www.theatlantic.com/science/archive/2015/10/the-genealogy-of-your- brain/408232/ |
AuthorsThe authors of these blog posts are staff writers of The Triple Helix at Georgetown University. Archives
November 2016
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