Download Genetics Lecture 13 Extranuclear Inheritance

3/7/2012
Genetics Lecture 13 Extranuclear Inheritance
Extranuclear Inheritance
• Throughout the history of genetics, occasional reports have challenged the basic tenet of Mendelian transmission genetics‐that the phenotype is transmitted by nuclear genes located on the chromosomes of both parents. • Observations have revealed inheritance patterns that fail to reflect Mendelian principles, and some indicate an apparent extranuclear influence on the phenotype. • Before the role of DNA in genetics was firmly established, such observations were commonly regarded with skepticism. •
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• There are several varieties of extranuclear inheritance. • One major type, referred to above, is also described as organelle heredity. – In this type of inheritance, DNA contained in mitochondria or chloroplasts determines certain phenotypic characteristics of the offspring. – Examples are often recognized on the basis of the uniparental transmission of these organelles, usually from the female parent through the egg to progeny. – A second type, called infectious heredity, results from a symbiotic or parasitic association with a microorganism
symbiotic or parasitic association with a microorganism. – In such cases, an inherited phenotype is affected by the presence of the microorganism in the cytoplasm of the host cells. – A third variety involves the maternal effect on the phenotype, whereby nuclear gene products are stored in the egg and then transmitted through the ooplasm to offspring. 3
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• These gene products are distributed to cells of the developing embryo and influence its phenotype. • The common element in all of these examples is the transmission of genetic information to offspring through the cytoplasm rather than through the nucleus, most often from only one of the parents. 4
Organelle Heredity Involves DNA in Chloroplasts and Mitochondria
• Before DNA was discovered in these organelles, the exact mechanism of transmission of the traits we are about to discuss was not clear, except that their inheritance appeared to be linked to something in the cytoplasm rather than to genes in the nucleus. • Most often (but not in all cases), the traits appeared to M t ft (b t t i ll
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be transmitted from the maternal parent through the ooplasm, causing the results of reciprocal crosses to vary. • Analysis of the inheritance patterns resulting from mutant alleles in chloroplasts and mitochondria has been difficult for two major reasons. 5
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• Second, large numbers of these organelles are contributed to each progeny cell following cell division. • lf only one or a few of the organelles acquire a new mutation or contain an existing one in a cell with a population of mostly normal organelles, the corresponding mutant phenotype may not be revealed, since the organelles lacking the mutation perform the wild‐type ll l ki
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function for the cell. • Such variation in the genetic content of organelles is called heteroplasmy. • Analysis is thus much more complex for traits controlled by genes encoded by organelle DNA than for Mendelian characters controlled by nuclear genes.
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Knowledge of Mitochondrial and Chloroplast DNA Helps Explain Organelle Heredity
• That both mitochondria and chloroplasts contain their own DNA and a system for expressing genetic information was first suggested by the discovery of mutations and the resultant inheritance patterns in plants, yeast, and other fungi. • Because both mitochondria and chloroplasts are inherited through the maternal cytoplasm in most organisms, and because examples of mutations could be linked hypothetically to the altered function
of mutations could be linked hypothetically to the altered function of either chloroplasts or mitochondria, geneticists set out to look for more direct evidence of DNA in these organelles. • Not only was unique DNA found to be a normal component of both mitochondria and chloroplasts, but careful examination of the nature of this genetic information would provide essential clues as to the evolutionary origin of these organelles. 7
Organelle DNA and the Endosymbiotic Theory • Electron microscopists not only documented the presence of DNA in mitochondria and chloroplasts, but they also saw that it exists there in a form quite unlike the form seen in
there in a form quite unlike the form seen in the nucleus of the eukaryotic cells that house these organelles. The
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endosymbiotic theory
• DNA in chloroplasts and mitochondria looks remarkably similar to the DNA seen in bacteria. • This similarity, along with the observation of the presence of a unique genetic system capable of organelle‐specific transcription and translation. • Basically, the endosymbiotic theory states that mitochondria and chloroplasts arose independently about 2 billion years ago from free‐living protobacteria
(primitive bacteria). •
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• This idea proposes that these ancient bacteria‐like cells were engulfed by larger primitive eukaryotic cells, which originally lacked the ability to respire aerobically or to capture energy from sunlight. • A beneficial, symbiotic relationship subsequently developed, whereby the bacteria eventually lost their ability to function autonomously, while the eukaryotic h t ll
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respiration or photosynthesis, as the case may be. • Although some questions remain unanswered, evidence continues to accumulate in support of this theory, and its basic tenets are now widely accepted. 11
• A brief examination of modern‐day mitochondria will help us better understand endosymbiotic theory. • During the course of evolution sub‐ sequent to the invasion event, distinct branches of diverse eukaryotic organisms arose. • As the evolution of the host cells progressed, the As the evolution of the host cells progressed, the
companion bacteria also underwent their own independent changes. • The primary alteration was the transfer of many of the genes from the invading bacterium to the nucleus of the host. 12
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• The products of these genes, though still functioning in the organelle, are nevertheless now encoded and transcribed in the nucleus and translated in the cytoplasm prior to their transport into the organelle. • The amount of DNA remaining today in the t pical mitochondrial genome is min sc le
typical mitochondrial genome is minuscule compared with that in the free‐living bacteria from which it was derived. • The most gene‐rich organelles now have fewer than 1O percent of the genes present in the smallest bacterium known
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Mutations in Mitochondrial DNA Cause Human Disorders
• The DNA found in human mitochondria has been completely sequenced and contains 16,569 base pairs. • As mentioned earlier, mtDNA gene products include 13 of over 70 proteins required for aerobic cellular respiration. respiration
• Because a cell’s energy supply is largely dependent on aerobic cellular respiration to generate ATP, disruption of any mitochondrial gene by mutation may potentially have a severe impact on that organism. • mtDNA is particularly vulnerable to mutations.
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• The number of copies of mtDNA in human cells can range from several hundred in somatic cells to approximately 100,000 copies of mtDNA in an oocyte. • Fortunately, a zygote receives a large number of organelles through the egg, so if only one organelle or a few of them contain a mutation, its impact is greatly diluted by the many mitochondria that lack the mutation and function normally. • However, during early development, cell division H
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disperses the initial population of mitochondria present in the zygote, and in the newly formed cells, these organelles reproduce autonomously.
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• In order for a human disorder to be attributable to genetically altered mitochondria, several criteria must be met: • 1. Inheritance must exhibit a maternal rather than a Mendelian pattern. • 2. The disorder must reflect a deficiency in the bioenergetic function of the organelle. • 3. There must be a mutation in one or more of the mitochondrial genes. 16
• Thus far, several disorders in humans are known to demonstrate these characteristics. • For example, myoclonic epilepsy and ragged‐red fiber disease (MERRF) demonstrates a pattern of inheritance consistent with maternal transmission. • Only the offspring of affected mothers inherit the disorder; the offspring of affected fathers are normal. • Individuals with this rare disorder express ataxia (lack of muscular coordination), deafness, dementia, and epileptic seizures. • The disease is so named because of the presence of “ragged‐red” f
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skeletal muscle fibers that exhibit blotchy red patches resulting from the proliferation of aberrant mitochondria. • Brain function, which has a high energy demand, is affected in this disorder, leading to the neurological symptoms described.
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Mitochondria, Human Health, and Aging
• The study of hereditary mitochondrial‐based disorders provides insights into the critical importance of this organelle during normal development. • In fact, mitochondrial dysfunction seems to be implicated in most all major disease conditions, including Type H (late‐
onset) diabetes atherosclerosis neurodegenerative
onset) diabetes, atherosclerosis, neurodegenerative diseases such as Parkinson, Alzheimer, and Huntington disease, schizophrenia and bipolar disorders, and a variety of cancers. • It is becoming evident, for example, that mutations in mtDNA are present in such human malignancies as skin, colorectal, liver, breast, pancreatic, lung, prostate, and bladder cancers.
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• Genetic tests for detecting mutations in the mtDNA genome that may serve as early‐stage disease markers have been developed. • For example, mtDNA mutations in skin cells have been detected as a biomarker of cumulative exposure of ultraviolet light and development of skin cancer. • However, it is still unclear whether mtDNA However it is still unclear whether mtDNA
mutations are causative effects contributing to development of malignant tumors or whether they are the consequences of tumor formation. •
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• The study of hereditary mitochondrial‐based disorders has also suggested a link between the progressive decline of mitochondrial function and the aging process. • It has been hypothesized that the accumulation of sporadic mutations in mtDNA leads to an increased prevalence of defective mitochondria (and the concomitant decrease in the supply of ATP) in cells over a lifetime. lif ti
• This condition in turn plays a significant role in aging. • It has been suggested that cells require a threshold level of ATP production resulting from oxidative phosphorylation for normal function. When the level drops below this threshold, the aging process is accelerated.
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In Maternal Effect, the Maternal Genotype Has a Strong Influence during Early Development • This is in contrast to biparental inheritance, where both parents transmit information on genes in the nucleus that d
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• In cases of maternal effect, the nuclear genes of the female gamete are transcribed, and the genetic products (either proteins or untranslated RNAs) accumulate in the egg cytoplasm. • After fertilization, these products are distributed among newly formed cells and influence the patterns or traits established during early development. 22
??? of the day Name: ______________________‐
• 1. In this type of inheritance, DNA contained in _________ or chloroplasts determines certain phenotypic characteristics of the offspring. • 2. First, the function of these organelles is dependent on gene products from both nuclear and organelle ______
• 3. As mentioned earlier, mtDNA gene products include ______ of over 70 proteins required for aerobic cellular respiration. • 4. _______tests for detecting mutations in the mtDNA genome that may serve as early stage disease markers have been developed
serve as early‐stage disease markers have been developed. • 5. In ___________ effect, also referred to as maternal influence, an offspring’s phenotype for a particular trait is under the control of nuclear gene products present in the egg. 23
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