Substitution mutation in genetics

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Substitution Mutation in Genetics: Definition and Types

A substitution mutation in genetics refers to a change where one nucleotide base is replaced by another in the DNA sequence. This can result in different types of mutations, such as transitions (purine to purine or pyrimidine to pyrimidine) and transversions (purine to pyrimidine or vice versa) . Substitution mutations can occur in both coding and non-coding regions of the genome, affecting gene function and evolution 25.

Patterns and Frequency of Substitution Mutations

Research shows that transition mutations (e.g., A↔G or C↔T) are generally more common than transversions . Additionally, there is a tendency for mutations to result in more adenine (A) or thymine (T) bases compared to guanine (G) or cytosine (C) . The pattern of nucleotide substitution is not entirely random; certain types of substitutions, such as guanine to adenine, occur more frequently in naturally occurring mutations . Hotspots for specific substitution mutations exist within the genome, often due to endogenous DNA lesions rather than replication errors .

Substitution Mutations and Evolutionary Processes

Substitution mutations play a key role in molecular evolution. The neutral mutation-random drift hypothesis suggests that many substitutions are neutral and become fixed in populations by chance, especially in small populations or during speciation events . However, slightly deleterious mutations can also become fixed, influencing the rate and pattern of evolution . The rate at which substitutions occur can be affected by population size, genetic diversity, and environmental changes 19.

Substitution Models in Molecular Evolution

Substitution models are used to describe and analyze the process of genetic variation through fixed mutations. These models have evolved to better mimic real evolutionary processes, accounting for differences in mutation rates and selection pressures across DNA, codon, and amino acid sequences . Accurate models are essential for understanding evolutionary dynamics and for selecting appropriate methods in evolutionary analysis .

Substitution Rate Versus Mutation Rate

The rate at which mutations arise (mutation rate) is often higher than the rate at which they become fixed in a population (substitution rate), especially when most mutations are slightly deleterious and are removed by purifying selection . This leads to a time-dependent effect, where short-term mutation rates appear higher than long-term substitution rates . Newer methods, such as the substitution-mutation rate ratio (c/μ), have been developed to provide a broader and more accurate assessment of selection pressure, especially in cases where traditional methods like the Ka/Ks ratio may be limited .

Non-Randomness and Directionality in Substitution Mutations

Substitution mutations do not occur randomly throughout the genome. There are significant departures from randomness, with certain nucleotide changes being more common due to underlying molecular mechanisms and selective pressures 47. The directionality and specificity of these mutations are influenced by DNA sequence context, cellular metabolism, and the presence of mutational hotspots .

Conclusion

Substitution mutations are a fundamental aspect of genetic variation and evolution. Their patterns are shaped by molecular mechanisms, selection pressures, and population dynamics. Understanding the frequency, directionality, and evolutionary consequences of substitution mutations is crucial for interpreting genetic data and modeling evolutionary processes 124567910.

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Most relevant research papers on this topic

Slightly Deleterious Mutant Substitutions in Evolution

Slightly deleterious mutations are important in evolution, potentially accelerating it in small populations or during speciation.

Highly Cited

1973·

1029citations

·T. Ohta

Patterns of nucleotide substitution in pseudogenes and functional genes

Transition mutations occur more frequently than transversion mutations, and nucleotide substitutions result more often in A or T than G or C, with functional genes showing similar patterns.

Highly Cited

2005·

262citations

·T. Gojobori et al.

Substitutions Are Boring: Some Arguments about Parallel Mutations and High Mutation Rates.

Parallel mutations and high mutation rates significantly shape genome architectures and genetic variation, challenging common models of evolutionary genetics.

2019·

40citations

·M. Press et al.

Evidence suggesting a non-random character to nucleotide replacements in naturally occurring mutations.

Natural mutations show a significant non-random character in nucleotide replacements, primarily due to a high incidence of guanine-to-adenine substitutions in amino acid codons.

Highly Cited

1967·

93citations

·Walter M. Fitch

Trends in substitution models of molecular evolution

Current substitution models of molecular evolution need further research for more realistic modeling and improved methods for selecting and analyzing models.

Highly Cited

2015·

130citations

·M. Arenas

Substitution-Mutation Rate Ratio (c/µ) As Molecular Adaptation Test Beyond Ka/Ks: A SARS-COV-2 Case Study.

The substitution-mutation rate ratio (c/) test is a more accurate method to detect selection pressure at a nucleotide site in a genome than the traditional Ka/Ks test, especially when synonymous mutations are neutral.

2025·

0citations

·Chun Wu et al.

Origins of spontaneous mutations: specificity and directionality of base-substitution, frameshift, and sequence-substitution mutageneses.

Spontaneous mutations arise from various sources, with hotspots in DNA sequences being more likely to result from endogenous DNA lesions than replication errors.

Highly Cited

2002·

164citations

·H. Maki

Substitution processes in molecular evolution. I. Uniform and clustered substitutions in a haploid model.

Substitutions in haploid populations are more regular in rapidly fluctuating environments and more clustered in slowly fluctuating environments, due to the increase in fitness with each substitution and the lowering of the effective mutation rate.

1993·

53citations

·John H. Gillespie

Is adaptation limited by mutation? A timescale-dependent effect of genetic diversity on the adaptive substitution rate in animals

Adaptation is limited by mutation supply in low-diversity species, but not at a larger taxonomic scale, suggesting that beneficial mutations scale downward with species' long-term population size.

2019·

65citations

·M. Rousselle et al.

Evidence for time dependency of molecular rate estimates.

The observed molecular rates may differ over time, with the substitution rate of mitochondrial protein-coding genes in birds and mammals being 0.01 substitutions/site/million years, and the mutation rate exceeding substitution rates in various organisms.

Highly Cited

2007·

279citations

·S. Ho et al.

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