E X T ERNAL SUBMISSION
Sexual Reproduction and Gametogenesis in Saccharomyces cerevisiae Implications for Replicative Aging RIYAD SEERVAI, BROWN UNIVERSITY ‘13
While aging makes the somatic body mortal, reproduction maintains the germ-line as immortal. In this paper, Riyad Seervai reviews findings showing that sexual reproduction in Saccharmoyces cerevisiae resets the replicative aging clock through a number of morphological and biochemical processes. I also discuss the connection between mating and aging in other model organisms. Introduction
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n 1885, Samuel Butler famously stated, “A hen is an egg’s way of making a new egg.” This revolutionary concept has had important ramifications on the way that scientists understand reproduction and longevity. The only way for a germ cell to pass on its DNA is through the intermediate of a free-living, independent organism that is capable of mating. Sexual selection drives the evolution of organisms in order to satisfy the needs of the germ line. Germ cells are thus immortal, able to defy time because they live on through the somatic cells of the body. However, studies in Saccharomyces cerevisiae from Dr. Angelica Amon’s Lab at MIT have shown that this is not always the case, and that somatic cells are able to defy time through germ line functions as well. Saccharomyces cerevisiae, commonly referred to as budding yeast or bakers’ yeast, has stood out as a model organism for understanding a variety of biological processes. The small size of its genome, the ease with which it can be manipulated, and its short life-cycle have made it a strong candidate for studies in reproduction, both sexual and vegetative. In recent years, yeast has also stood out as a prime candidate for studies of cellular and organismal aging (1), due to their cells’ finite replicative capacity (2). This paper shows how these two biological processes – reproduction and gamete formation, and aging – are connected in ways that were previously unknown. The paper describes WINTER 2013
Figure 1: Genetic characterization of the mating cycle in S. cerevisiae. a and α cells express different genes that are involved in attracting the other mating type during sexual reproduction. Reproduced from (4).
the processes of sexual reproduction and aging in S. cerevisiae. Then, it proceeds to analyze Amon’s studies in order to provide an understanding of how the two processes defy Chronos and Thanatos, thus maintaining the unsolved mystery of the chicken and the egg.
Yeast Mating 101 The history of mating in S. cerevisiae dates back to over half a century ago. It was determined that when conditions are favorable, two haploid yeast spores fuse together in order to form a diploid hybrid cell (3). This required that the cells be viable, remain in a haploid state, and have opposite mating types. It was surprising to note that budding yeast was not a simple, asexual organism. On the contrary, yeast have two mating type (MAT) loci, MATa and MATα, which confer a and α mating types to the haploid cells. The loci have been genetically determined (4), and it has been shown that the MATa1 locus
activates a-specific genes (asg) responsible for the production of a-pheromone and a receptor for the α–factor. The α locus contains two loci, MATα1 and MATα2, which are responsible for suppressing the a-specific genes (α1) and activating the α-specific genes (α2). Both a and α cells express haploid-specific genes (hsg), which are involved in the mating process. In order for two heterothallic yeast cells to mate and form a diploid, they must be attracted to each other. The a cell releases a-factor (or pheromone) that lands on the α cell’s receptor for a-pheromone. The α cell attracts the a cell in a similar fashion (5). Upon sensing the opposite mating pheromone, the cells get arrested in an unbudded stage of the cell cycle in which DNA replication has not yet taken place – that is, the cells are still haploid (6). This is the optimal stage during which nuclear fusion, DNA replication, and meiosis can occur without lethal mistakes (7). The arrested cells now undergo an alteration in morphology to form elongated, 39