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BOLIVARIAN REPUBLIC OF VENEZUELA UNIVERSIDAD DEL ZULIA NEUROSCIENCES INSTITUTE GENETICS OF COMMON HERITABLE DISORDERS IN VENEZUELA RESEARCH TRAINING PROGRAM PROFESSOR: GLADYS MAESTRE, M.D RISING TO FIXATION Final Essay JOSELYN ROJAS QUINTERO, M.D ID. 13.933.162 Maracaibo, December 2005 Rising to Fixation A freshly duplicated selfish element is likely to be slightly deleterious because it takes up space in the genome and also makes use of the cell’s transcription and translation machinery for a function that not only does not contribute to the cell but wastes energy as well. Explain in terms of selection and drift why, in spite of the above consideration, the element can rise to fixation in the population. By definition, a selfish gene works only for itself, using any mean necessary for its survival in the next generations1. And by any mean, it includes the destruction of other genes while it is inserted in the DNA, and, the unique ability to multiply inside the genome so that the gene can have as many copies as it can. This intrinsic replication machinery that selfish elements have facilitates their fixation within the genome, even though, they might not even have a specific function, or worse, they can have disadvantageous effects on the host’s survival. The fixation of this type of genes depends mainly on two aspects: the selfish capacity of its replication and the method of fixation. The ability of the selfish gene to multiply within its host’s genome and to be able to replicate in the free-genomes is what I call selfish capacity. Since all mutations (good, trivial or bad) always occur in an individual’s germline, this gene has to duplicate intra-genome to ensure its survival in this specific individual, but its necessity to “colonize” non-selfish-elements genomes is what makes this sequence so enigmatic. Given that we are diploid individuals, one haploid genome is colonized and the other isn’t, so during the formation of the first 2 cells of the zygote the gene has to virtually “jump” (almost infectiously) and introduce itself in the non-colonized genome2 “conquering” it (intergenomic multiplication in the free haploid DNA). This process is, of course, done in a non-mendelian fashion. It’s clear that this kind of gene is a transposable sequence which has intragenomic replication machinery, and it multiplies at a certain frequency. The more it copies the higher the frequency of it in the next generation, although a lower rate of multiplication doesn’t alter the spreading since the intergenomic capacity of colonization is what keeps it in the future populations 2; the only thing that will change is the number of copies in each individual’s genome. So a “selfisher” gene would be one that has various copies inside the DNA of the host, made at a high rate, and can colonize faster the zygote´s cells. Only it can ensure its survival, and that is being quicker than the other transposable elements. The tricky question is what happens if this gene lowers the fitness of the individual who carries it? It would have to be a very disadvantageous trait – lethal or sterility related – to eliminate the host (extinct the gene). If the gene only lowers the fitness then is just a matter of “selecting” the method of fixation. In this case the gene “takes up space in the genome” and “wastes energy”, so apparently it doesn’t interfere strongly with the reproductive capacities. By Darwin’s definition3 during natural selection only the fittest survive, being this the one that has more reproductive capabilities, ensuring a good number of offprings that will continue the species. In a genomic level, the “fit individual” is without a doubt a quick selfish gene. Even if the gene lowers the fitness, the host will continue to procreate (at least 1 offspring) that will carry the gene and its copies, and since it doesn’t produce a contra productive phenotype trait, selection “lets it pass”. This is true unless during the next generations, the copies alters genomic sequences that regulate procreation, at this point, selection will eliminate it. Based on Darwin’s observations, the population will reproduce in an infinite matter, but, what happens if by chance a natural disaster or a plague occurs? The population will be shortened and the ones who survive will be selected by chance not selection. Let’s assume that the survivors have the selfish gene, and being in this bottleneck situation they will multiply to increase the population number, passing the gene to all their descendants. Hence, this gene was then fixated by a genetic drift method. Another drift way to fixate a gene is the so called “founder effect” where one individual settles in a new small population genetically different from him. Since the matting will be likely non-random in the course of the following generations the gene will be passed along in a Mendelian fashion, until every genome has it (frequency 1). But keep in mind that a non-selfish-element genome is the playground of a quick selfish gene, so the new population genome colonization will be “just a walk in the park” (so to speak). In other words, it seems that a “selfisher” gene would be better fixated during genetic drift situations, although with a closer look, a fast-multiplying self-replicating gene fits better the description of Darwin’s key to survival. To summarize, a selfish gene is a genomic sequence with self-replicating properties that can be fixated into the genome, even if it offers no benefits to the host or group of individuals. This kind of sequence can be fixated by natural selection or genetic drift, always depending of its own replicating characteristics. CITED REFERENCES 1. DAWKINS, R. 1976 The Selfish Gene. Oxford University Press, Oxford. 2. HICKEY, D. “Selfish DNA: a sexually tranbsmitted nuclear parasite”. Genetics 1982;101:519-53. 3. FLEMING C, GOODALL J. “Dangerous Darwin”. Public Understand Sci 2002;11:259-71.