RESUMO
Selection is expected to be more efficient in species that are more diverse because both the efficiency of natural selection and DNA sequence diversity are expected to depend upon the effective population size. We explore this relationship across a data set of 751 mammal species for which we have mitochondrial polymorphism data. We introduce a method by which we can examine the relationship between our measure of the efficiency of natural selection, the nonsynonymous relative to the synonymous nucleotide site diversity (πN/πS), and synonymous nucleotide diversity (πS), avoiding the statistical non-independence between the two quantities. We show that these two variables are strongly negatively and linearly correlated on a log scale. The slope is such that as πS doubles, πN/πS is reduced by 34%. We show that the slope of this relationship differs between the two phylogenetic groups for which we have the most data, rodents and bats, and that it also differs between species with high and low body mass, and between those with high and low mass-specific metabolic rate.
Assuntos
DNA Mitocondrial/genética , Mamíferos/genética , Polimorfismo Genético , Seleção Genética , Animais , Metabolismo Basal , Tamanho Corporal , Quirópteros/genética , Simulação por Computador , Modelos Genéticos , Densidade Demográfica , Roedores/genética , Análise de Sequência de DNARESUMO
It has been suggested that sexual reproduction is maintained because it reduces the load imposed by recurrent deleterious mutations. If rates of deleterious mutation per diploid genome per generation (U) exceed 1, and mutations interact synergistically, then sexuals can overcome their inherent twofold disadvantage. We have tested this hypothesis by estimating genomic point mutation rates for protein-coding genes in a range of animal taxa. We find a positive linear relationship between U and generation time. In species with short generation times, U is predicted to be far below 1, suggesting that sex is not maintained by its capacity to purge the genome of deleterious mutations.
Assuntos
Evolução Biológica , Mutação Puntual , Sexo , Animais , Aves/genética , Aves/fisiologia , Gatos/genética , Gatos/fisiologia , Bovinos/genética , Bovinos/fisiologia , Elementos de DNA Transponíveis , Cães/genética , Cães/fisiologia , Drosophila/genética , Drosophila/fisiologia , Feminino , Haplorrinos/genética , Haplorrinos/fisiologia , Humanos , Masculino , Mutação , Proteínas/genética , Roedores/genética , Roedores/fisiologia , Ovinos/genética , Ovinos/fisiologiaRESUMO
The assumption that human mitochondrial DNA is inherited from one parent only and therefore does not recombine is questionable. Linkage disequilibrium in human and chimpanzee mitochondrial DNA declines as a function of the distance between sites. This pattern can be attributed to one mechanism only: recombination.
Assuntos
DNA Mitocondrial/genética , Hominidae/genética , Desequilíbrio de Ligação , Pan troglodytes/genética , Recombinação Genética , Animais , Evolução Molecular , Pai , Feminino , Humanos , Masculino , NADH Desidrogenase/genética , Polimorfismo de Fragmento de RestriçãoRESUMO
An interplay among experimental studies of protein synthesis, evolutionary theory, and comparisons of DNA sequence data has shed light on the roles of natural selection and genetic drift in 'silent' DNA evolution.
Assuntos
Evolução Molecular , Biossíntese de Proteínas , Animais , DNA/genética , HumanosRESUMO
The 'mutational deterministic' hypothesis proposes that a high genomic rate of deleterious mutation (U) might maintain sexual reproduction. Our recent work casts doubt on this, as we estimate a low U for sexually reproducing species with short generation times. Following criticism by Kondrashov, here we defend our methods for estimating U and challenge the mutational deterministic hypothesis.
Assuntos
Mutação , Razão de Masculinidade , Animais , Evolução Biológica , Códon , HumanosRESUMO
It has been suggested that mutation bias is the major determinant of base composition bias at synonymous, intron, and flanking DNA sites in mammals. Here I test this hypothesis using population genetic data from the major histocompatibility genes of several mammalian species. The results of two tests are inconsistent with the mutation hypothesis in coding, noncoding, CpG-island, and non-CpG-island DNA, but are consistent with selection or biased gene conversion. It is argued that biased gene conversion is unlikely to affect silent site base composition in mammals. The results therefore suggest that selection is acting upon silent site G + C content. This may have broad implications, since silent site base composition reflects large-scale variation in G + C content along mammalian chromosomes. The results therefore suggest that selection may be acting upon the base composition of isochores and large sections of junk DNA.
Assuntos
Composição de Bases/genética , Mamíferos/genética , Seleção Genética , Alelos , Animais , Ilhas de CpG/genética , DNA/genética , Evolução Molecular , Regulação da Expressão Gênica , Frequência do Gene , Genética Populacional , Humanos , Complexo Principal de Histocompatibilidade/genética , Camundongos , Modelos Genéticos , Mutação , Polimorfismo Genético , Análise de Sequência de DNA , Estatística como AssuntoRESUMO
It has been shown previously that the synonymous substitution rate between Escherichia coli and Salmonella typhimurium is lower in highly than in weakly expressed genes, and it has been suggested that this is due to stronger selection for translational efficiency in highly expressed genes as reflected in their greater codon usage bias. This hypothesis is tested here by comparing the substitution rate in codon families with different patterns of synonymous codon use. It is shown that the decline in the substitution rate across expression levels is as great for codon families that do not appear to be subject to selection for translational efficiency as for those that are. This implies that selection on translational efficiency is not responsible for the decline in the substitution rate across genes. It is argued that the most likely explanation for this decline is a decrease in the mutation rate. It is also shown that a simple evolutionary model in which synonymous codon use is determined by a balance between mutation, selection for an optimal codon, and genetic drift predicts that selection should have little effect on the substitution rate in the present case.
Assuntos
Códon/genética , Enterobacteriaceae/genética , Modelos Genéticos , Mutação , Biossíntese de Proteínas , Escherichia coli/genética , Evolução Molecular , Frequência do Gene , Salmonella typhimurium/genética , Seleção Genética , Alinhamento de SequênciaRESUMO
Several lines of evidence are presented which suggest that sequence G + C content and recombination frequency are related in mammals: (i) chromosome G + C content is positively correlated to chiasmata density; (ii) the non-pairing region of the Y chromosome has one of the lowest G + C contents of any chromosomal segment; (iii) a reduction in the rate of recombination at several loci is mirrored by a decrease in G + C content; and (iv) when compared with humans, mice have a lower variance in chiasmata density which is reflected in a lower variance in G + C content. The observed relation between recombination frequency and sequence G + C content provides an elegant explanation of why gene density is higher in G + C rich isochores than in other parts of the genome, and why long interspersed elements (LINES) are exclusive to G + C poor isochores. However, the cause of the relation is as yet unknown. Several possibilities are considered, including gene conversion.
Assuntos
Composição de Bases , Evolução Biológica , Genoma , Mamíferos/genética , Modelos Genéticos , Recombinação Genética , Animais , Troca Genética , Reparo do DNA , Feminino , Conversão Gênica , Frequência do Gene , Masculino , Camundongos/genética , Primatas/genética , Sequências Repetitivas de Ácido Nucleico , Cromossomo YRESUMO
Phylogenetic trees constructed using human mitochondrial sequences contain a large number of homoplasies. These are due either to repeated mutation or to recombination between mitochondrial lineages. We show that a tree constructed using synonymous variation in the protein coding sequences of 29 largely complete human mitochondrial molecules contains 22 homoplasies at 32 phylogenetically informative sites. This level of homoplasy is very unlikely if inheritance is clonal, even if we take into account base composition bias. There must either be 'hypervariable' sites or recombination between mitochondria. We present evidence which suggests that hypervariable sites do not exist in our data. It therefore seems likely that recombination has occurred between mitochondrial lineages in humans.
Assuntos
DNA Mitocondrial/genética , Haplorrinos/genética , Proteínas/genética , Animais , Sequência de Bases , Células Clonais , Variação Genética , Hominidae/genética , Humanos , Hylobates/genética , Modelos Genéticos , Dados de Sequência Molecular , FilogeniaRESUMO
A strong negative correlation between the rate of amino-acid substitution and codon usage bias in Drosophila has been attributed to interference between positive selection at nonsynonymous sites and weak selection on codon usage. To further explore this possibility we have investigated polymorphism and divergence at three kinds of sites: synonymous, nonsynonymous and intronic in relation to codon bias in D. melanogaster and D. simulans. We confirmed that protein evolution is one of the main explicative parameters for interlocus codon bias variation (r(2) approximately 40%). However, intron or synonymous diversities, which could have been expected to be good indicators of local interference [here defined as the additional increase of drift due to selection on tightly linked sites, also called 'genetic draft' by Gillespie (2000)] did not covary significantly with codon bias or with protein evolution. Concurrently, levels of polymorphism were reduced in regions of low recombination rates whereas codon bias was not. Finally, while nonsynonymous diversities were very well correlated between species, neither synonymous nor intron diversities observed in D. melanogaster were correlated with those observed in D. simulans. All together, our results suggest that the selective constraint on the protein is a stable component of gene evolution while local interference is not. The pattern of variation in genetic draft along the genome therefore seems to be instable through evolutionary times and should therefore be considered as a minor determinant of codon bias variance. We argue that selective constraints for optimal codon usage are likely to be correlated with selective constraints on the protein, both between codons within a gene, as previously suggested, and also between genes within a genome.
Assuntos
Códon/genética , Drosophila/genética , Evolução Molecular , Genoma/genética , Polimorfismo Genético , Seleção Genética , Animais , Especificidade da EspécieRESUMO
The spatial distribution of synonymous substitutions in enterobacterial genes is investigated. It is shown that synonymous substitutions are significantly clustered in such a way that a synonymous substitution in one codon elevates the rate of synonymous substitution in an adjacent codon by about 10%. The level of clustering does not appear to be related to the level of gene expression, and it is restricted to a range of two or three codons. There are at least three possible explanations: (1) sequence-directed mutagenesis, (2) recombination, and (3) selection.
Assuntos
Análise por Conglomerados , Enterobacteriaceae/genética , Genes Bacterianos/genética , Código Genético , Variação Genética , Sequência de Bases , Escherichia coli/genética , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida/genética , Recombinação Genética/genética , Salmonella typhimurium/genética , Seleção GenéticaRESUMO
Until very recently, mitochondria were thought to be clonally inherited through the maternal line in most higher animals. However, three papers published in 2000 claimed population-genetic evidence of recombination in human mitochondrial DNA. Here I review the current state of the debate. I review the evidence for the two main pathways by which recombination might occur: through paternal leakage and via a mitochondrial DNA sequence in the nuclear genome. There is no strong evidence for either pathway, although paternal leakage seems a definite possibility. However, the population-genetic evidence, although not conclusive, is strongly suggestive of recombination in mitochondrial DNA. The implications of non-clonality for our understanding of human and mitochondrial evolution are discussed.
Assuntos
DNA Mitocondrial , Recombinação Genética , Animais , Humanos , Desequilíbrio de Ligação , MitocôndriasRESUMO
It has been suggested that the differences in synonymous codon use between mammalian genes within a genome are due to differences in the efficiency of DNA mismatch repair. This hypothesis was tested by developing a model of mismatch repair, which was used to predict the expected relationship between the rate of substitution and G+C content at silent sites. It was found that the silent-substitution rate should decline with increasing G+C content over most of the G+C-content range, if it is assumed that mismatch repair is G+C biased, an assumption which is supported by data. This prediction was then tested on a set of 58 primate and artiodactyl genes. There was no evidence of a direct decline in substitution rate with increasing G+C content, for either twofold- or fourfold-degenerate sites. It was therefore concluded that variation in the efficiency of mismatch repair is not responsible for the differences in synonymous codon use between mammalian genes. In support of this conclusion, analysis of the model also showed that the parameter range over which mismatch repair can explain the differences in synonymous codon use between genes is very small.
Assuntos
Evolução Biológica , Códon/genética , Reparo do DNA/genética , Mamíferos/genética , Animais , Composição de Bases , Simulação por Computador , Modelos GenéticosRESUMO
It is shown that synonymous codon usage is less biased in favor of those codons preferred by highly expressed genes at the end of Escherichia coli genes than in the middle. This appears to be due to the close proximity of many E. coli genes. It is shown that a substantial number of genes overlap either the Shine-Dalgarno sequence or the coding sequence of the next gene on the chromosome and that the codons that overlap have lower synonymous codon bias than those which do not. It is also shown that there is an increase in the frequency of A-ending codons, and a decrease in the frequency of G-ending codons at the end of E. coli genes that lie close to another gene. It is suggested that these trends in composition could be associated with selection against the formation of mRNA secondary structure near the start of the next gene on the chromosome. Stop codon use is also affected by the close proximity of genes; many genes are forced to use TGA and TAG stop codons because they terminate either within the Shine-Dalgarno or coding sequence of the next gene on the chromosome. The implications these results have for the evolution of synonymous codon use are discussed.
Assuntos
Códon de Terminação/genética , Escherichia coli/genética , Genes Bacterianos , Sequência de Bases , Sítios de Ligação , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Escherichia coli/metabolismo , Evolução Molecular , Expressão Gênica , Dados de Sequência Molecular , RNA Bacteriano/genética , RNA Bacteriano/metabolismo , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Ribossomos/metabolismoRESUMO
It has been suggested that isochores are maintained by mutation biases, and that this leads to variation in the rate of mutation across the genome. A model of DNA replication is presented in which the probabilities of misincorporation and proofreading are affected by the composition and concentration of the free nucleotide pools. The relationship between sequence G+C content and the mutation rate is investigated. It is found that there is very little variation in the mutation rate between sequences of different G+C contents if the total concentration of the free nucleotides remains constant. However, variation in the mutation rate can be arbitrarily large if some mismatches are proofread and the total concentration of free nucleotides varies. Hence the model suggests that the maintenance of isochores by the replication of DNA in free nucleotide pools of biased composition does not lead per se to mutation rate variance. However, it is possible that changes in composition could be accompanied by changes in concentration, thus generating mutation rate variance. Furthermore, there is the possibility that germ-line selection could lead to alterations in the overall free nucleotide concentration through the cell cycle. These findings are discussed with reference to the variance in mammalian silent substitution rates.
Assuntos
Composição de Bases , Replicação do DNA , Variação Genética/genética , Mamíferos/genética , Modelos Genéticos , Mutação , Animais , Reparo do DNARESUMO
Since the G + C content of a gene is correlated to that of the isochore in which it resides, and early replicating isochores are thought to be relatively G + C rich, early replicating genes should also be rich in G + C. This hypothesis is tested on a sample of 44 mammalian genes for which replication time data and sequence information are available. Early replicating genes do not appear to be more G + C rich than late replicating genes, instead there is considerable variation in the G + C content of genes replicated during both halves of S phase. These results show that both G + C rich and poor fractions of the genome are replicated early and late in the cell cycle, and suggest that isochores are not maintained by the replication of DNA sequences in compositionally biased free nucleotide pools.