Deleterious mutations

Genetic Control. Manipulation of the mechanisms of inheritance of the insect pest populations has occurred most successhiUy through the mass release of steri1i2ed males, but a variety of other techniques have been studied, including the environmental use of chemostetilants and the mass introduction of deleterious mutations, eg, conditional lethals and chromosomal translocations (58 ndash 60) (see Genetic engineering). 

Initially, it was assumed that the HlV-1 population is infinite, evolution is deterministic, and antiretroviral resistance development is definite (Coffin 1995). However, our research amongst others has demonstrated that the effective population size, defined as the average number of HIV variants that produces infectious progeny is relatively small (Leigh Brown 1997 Leigh Brown and Richman 1997 Nijhnis et al. 1998). This can be explained because the majority of virus particles that are produced harbor deleterious mutations resulting in noninfectious virus. Also limited target cell availability and inactivation of potentially infectious viruses by the host... 

Wild female house mice, Mus musculus, prefer the odor of males with the t-complex wild genotype over males with deleterious mutations (- -/t) at the... 

It should be born in mind that normal MRC activity can be found in an organ or a tissue that does not clinically express the disease. One might deal with a tissue-specific organ deficiency, as observed in Friedreich s ataxia where iron-sulfur deficiency is barely detectable in skeletal muscle or skin fibroblasts [57]. Tissue specificity is far from being understood it is often observed even in the case of patients harboring deleterious mutation in nuclear genes with widespread expression in the organism [9]. 

It is presumably the ability to survive as a heterozygote, even with one or more highly deleterious mutations, that has led to the dominance of the diploid phase in higher plants and animals.76 However, to the biochemical geneticist organisms with a haploid phase offer experimental advantages because recessive mutants can be detected readily. 

Sex helps to remove deleterious mutations from a population.243 A large fraction of human fetuses (at least 10-25%) contain an "incorrect" number of chromosomes and as many as 20% of oocytes are defective. In contrast only 3-4% of sperm are chromosomally abnormal. Female meiosis I appears to be highly error-prone.243a Abnormal fertilized eggs or embryos are eliminated later in development. 

The health consequence of deleterious mutation in populations is poorly understood, despite the large effort that has been expended in the study of mutation. Spontaneous-mutation rates are known only roughly, the forces that maintain or alter gene frequencies in populations are not well understood, and the relative impacts of different types of mutations are obscure. 

The human situation is not understood, but it is possible that, for every severe mutation detected by laboratory test systems, 20 or more mildly deleterious mutations also occur. 

As a search technique, using mutation and selection alone has several limitations. Evolution via asexual reproduction tends to build up deleterious mutations, ultimately limiting the potential of the experiment, an effect known as Muller s ratchet (Muller, 1964). This effect is exacerbated by high mutagenesis rates, as slightly deleterious amino acid substitutions can hitchhike with positive mutations. Recombination can act to remove neutral and deleterious mutations while allowing the accumulation of... 

Elena SF, Lenski RE (1997) Test of synergistic interactions among deleterious mutations in bacteria. Nature 390 395-398... 

Keightley PD, Eyre-Walker A (2000) Deleterious mutations and the evolution of sex. Science... 

Koedoed S, Otten ME, Koebmann BJ, Bruggeman FJ, Bakker BM, Snoep JL, Krab K, van Spanning RJM, van Verseveld HW, Jensen PR, Koster JG, Westerhoff HV (2002) A turbo engine with automatic transmission How to marry chemicomotion to the subtleties and robustness of life. Biochim Biophys Acta 1555 75-82 Kondrashov AS (1988) Deleterious mutations and the evolution of sexual reproduction. Nature 336 435-440... 

CNS have the highest demand of all the cells in the body for OXPHOS to provide ATP for normal function. Cardiac and skeletal muscle have the next highest need for OXPHOS, while the endocrine system and skin have lesser requirements for OXPHOS. Thus, as mitochondrial function fails due to deleterious mutations in mtDNA, often the earliest manifestations of such mitochondrial distress is seen in neurological and muscular abnormalities. 

There are conditions under which mildly deleterious mutations could contribute to protein evolution. If a second mutation occurs in a protein-coding gene that has experienced a deleterious mutation, it might compensate for the harmful effect of the first. If the doubly mutated gene were functionally equivalent to the wild-type gene, it would be fixed by genetic drift. 

For normal cell growth and proliferation, the DNA must be protected from various types of damage. Such damage, induced, for example, by uv irradiation, can involve the chemical alteration of the DNA and, consequently, deleterious mutation. Cells are able to correct or repair such damage. One of the best-understood mechanisms of repair involves the synthesis of new DNA, which replaces the damaged portion. This is called repair synthesis of DNA. The extent of repair synthesis is very small in comparison with the DNA synthesis accompanying replication of the chromosomes. 

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