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The function of protein and RNA molecules depends on complex epistatic interactions between sites. Therefore, the deleterious effect of a mutation can be suppressed by a compensatory second-site substitution. In relating a list of 86 pathogenic mutations in human tRNAs encoded by mitochondrial genes to the sequences of their mammalian orthologs, we noted that 52 pathogenic mutations were present in normal tRNAs of one or several nonhuman mammals. We found at least five mechanisms of compensation for 32 pathogenic mutations that destroyed a Watson-Crick pair in one of the four tRNA stems: restoration of the affected Watson-Crick interaction (25 cases), strengthening of another pair (4 cases), creation of a new pair (8 cases), changes of multiple interactions in the affected stem (11 cases) and changes involving the interaction between the loop and stem structures (3 cases). A pathogenic mutation and its compensating substitution are fixed in a lineage in rapid succession, and often a compensatory interaction evolves convergently in different clades. At least 10%, and perhaps as many as 50%, of all nucleotide substitutions in evolving mammalian tRNAs participate in such interactions, indicating that the evolution of tRNAs proceeds along highly epistatic fitness ridges. 相似文献
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Selection for short introns in highly expressed genes 总被引:1,自引:0,他引:1
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Deleterious mutations and the evolution of sexual reproduction 总被引:48,自引:0,他引:48
A S Kondrashov 《Nature》1988,336(6198):435-440
The origin and maintenance of sexual reproduction continues to be an important problem in evolutionary biology. If the deleterious mutation rate per genome per generation is greater than 1, then the greater efficiency of selection against these mutations in sexual populations may be responsible for the evolution of sex and related phenomena. In modern human populations detrimental mutations with small individual effects are probably accumulating faster than they are being eliminated by selection. 相似文献
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Haploidy or diploidy: which is better? 总被引:17,自引:0,他引:17
Although the evolutionary advantages of sexual reproduction have been extensively discussed, much less attention has been paid to haploid and diploid phases of the sexual life cycle. The relative lengths of these phases differ greatly in various taxa, including as extremes those with one or the other phase reduced to a single cell. Here we consider the efficiency of elimination of deleterious mutations as an evolutionary force and compare the mutation loads under haploid and diploid selection, Ln and L2n. With truncation-like selection, partial dominance, and heterozygous effect of a mutation less than about 1/4 its hemizygous effect, L2n less than Ln; otherwise L2n greater than Ln. The difference becomes important when the genomic deleterious mutation rate exceeds about 1 per genome. This suggests that the mutation rate, degree of dominance and mode of selection can be important in life-cycle evolution. 相似文献
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Sympatric speciation, the origin of two or more species from a single local population, has almost certainly been involved in formation of several species flocks, and may be fairly common in nature. The most straightforward scenario for sympatric speciation requires disruptive selection favouring two substantially different phenotypes, and consists of the evolution of reproductive isolation between them followed by the elimination of all intermediate phenotypes. Here we use the hypergeometric phenotypic model to show that sympatric speciation is possible even when fitness and mate choice depend on different quantitative traits, so that speciation must involve formation of covariance between these traits. The increase in the number of variable loci affecting fitness facilitates sympatric speciation, whereas the increase in the number of variable loci affecting mate choice has the opposite effect. These predictions may enable more cases of sympatric speciation to be identified. 相似文献
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Jordan IK Kondrashov FA Adzhubei IA Wolf YI Koonin EV Kondrashov AS Sunyaev S 《Nature》2005,433(7026):633-638
Amino acid composition of proteins varies substantially between taxa and, thus, can evolve. For example, proteins from organisms with (G + C)-rich (or (A + T)-rich) genomes contain more (or fewer) amino acids encoded by (G + C)-rich codons. However, no universal trends in ongoing changes of amino acid frequencies have been reported. We compared sets of orthologous proteins encoded by triplets of closely related genomes from 15 taxa representing all three domains of life (Bacteria, Archaea and Eukaryota), and used phylogenies to polarize amino acid substitutions. Cys, Met, His, Ser and Phe accrue in at least 14 taxa, whereas Pro, Ala, Glu and Gly are consistently lost. The same nine amino acids are currently accrued or lost in human proteins, as shown by analysis of non-synonymous single-nucleotide polymorphisms. All amino acids with declining frequencies are thought to be among the first incorporated into the genetic code; conversely, all amino acids with increasing frequencies, except Ser, were probably recruited late. Thus, expansion of initially under-represented amino acids, which began over 3,400 million years ago, apparently continues to this day. 相似文献