Evolutionary honing in and mutational replacement: how long-term directed mutational responses to specific environmental pressures are possible

Livnat, Adi; Melamed, Daniel R.

doi:10.1007/s12064-023-00387-z

Cited by 3 publications

(15 citation statements)

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“…Examples of molecular mechanisms leading to complex conditioned mutations (CCMs) (Figure modified from [50]): In each of the panels, evolutionary time is represented with the broader arrows, showing the consequences of evolutionary changes, while the thinner arrows and other elements represent processes occurring in "developmental time" or within the lifetime of the organism. These within-organism and correlation between gene interaction and gene fusion given that neighboring genes are more likely to be working together.…”

Section: Empirical Evidence For Complex Conditioned Mutationmentioning

confidence: 99%

“…In addition, this mechanistic determination occurs in a biologically meaningful manner. For example, genes whose products are required in excess amounts are more likely to undergo a duplication mutation [50,[62][63][64][65][66] (see Figure 1).…”

Section: Objections: Modifier Theory Mutator Alleles and Hypermutabilitymentioning

confidence: 99%

“…[53] (B) Gene duplication: Selection pressure leading to a high transcriptional activity of a certain gene makes this gene more likely to undergo a duplication mutation over the generations due to transcription-associated genome instability. [49,50] (C) A-to-G RNA editing activity whose frequency at certain RNA sites increases over evolutionary time increases the rate of A-to-G DNA mutations at the corresponding positions in the DNA via several possible mechanisms, such as reverse transcriptase activity of several DNA polymerases using edited RNA as a template. [50] (D) CCMs facilitate evolutionary change by generating new, heritable genomic units based on regulatory information already present in the genome as a system, which derive from configurations specific to each heritable change that have been evolutionarily beneficial in the past.…”

Section: Objections: Modifier Theory Mutator Alleles and Hypermutabilitymentioning

confidence: 99%

“…[49,50] (C) A-to-G RNA editing activity whose frequency at certain RNA sites increases over evolutionary time increases the rate of A-to-G DNA mutations at the corresponding positions in the DNA via several possible mechanisms, such as reverse transcriptase activity of several DNA polymerases using edited RNA as a template. [50] (D) CCMs facilitate evolutionary change by generating new, heritable genomic units based on regulatory information already present in the genome as a system, which derive from configurations specific to each heritable change that have been evolutionarily beneficial in the past. [50] Modifier theory is well developed mathematically and constitutes an important resource in the arsenal of evolutionary genetics.…”

Section: Objections: Modifier Theory Mutator Alleles and Hypermutabilitymentioning

confidence: 99%

“…Possibly, but there are multiple empirical observations consistent with the CCM picture (Figure 1). [50,53] It is also important to note that the HbS case has traditionally been invoked as a central empirical example of random mutation and natural selection. [98,99] Thus, other seemingly clear-cut examples of random mutation, such as those studied with the fluctuation test, may need to be revisited with the new category of CCMs in view.…”

Section: Ramifications: Revisiting a Classic Experimentsmentioning

confidence: 99%

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Mutation and evolution: Conceptual possibilities

Livnat,

Love

2024

BioEssays

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Although random mutation is central to models of evolutionary change, a lack of clarity remains regarding the conceptual possibilities for thinking about the nature and role of mutation in evolution. We distinguish several claims at the intersection of mutation, evolution, and directionality and then characterize a previously unrecognized category: complex conditioned mutation. Empirical evidence in support of this category suggests that the historically famous fluctuation test should be revisited, and new experiments should be undertaken with emerging experimental techniques to facilitate detecting mutation rates within specific loci at an ultra‐high, individual base pair resolution.

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Section: Empirical Evidence For Complex Conditioned Mutationmentioning

confidence: 99%

Section: Objections: Modifier Theory Mutator Alleles and Hypermutabilitymentioning

confidence: 99%

Section: Objections: Modifier Theory Mutator Alleles and Hypermutabilitymentioning

confidence: 99%

Section: Objections: Modifier Theory Mutator Alleles and Hypermutabilitymentioning

confidence: 99%

Section: Ramifications: Revisiting a Classic Experimentsmentioning

confidence: 99%

See 3 more Smart Citations

Mutation and evolution: Conceptual possibilities

Livnat,

Love

2024

BioEssays

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Past, Present, and Future of RNA Modifications in Infectious Disease Research

Pan,

Bruch,

Blango

2024

ACS Infect. Dis.

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impossible. Here, we aim to add to the importance of this seminal report with additional insights into where the field of RNA modification research intersects that of infection biology. We provide a more elaborate description of key references and posit just a few ways that the success of the proposed path from the NASEM report could change the way we consider infectious diseases. We encourage the readers of this perspective to also visit the NASEM report to better appreciate the entire landscape of RNA modifications research, through the lens of many of the very researchers that made seminal discoveries to establish the field.■ WHAT IS AN RNA MODIFICATION AND HOW DO WE MAP THEM?RNA is decorated with over 170 known chemical modifications that influence RNA function, stability, structure, and interaction with other macromolecules including nucleic acids and proteins. These chemical modifications range from small alterations like methylations and acetylations to bulky modifications like those of glutamyl-queuosine (GluQ) or 5c a r b o x y m e t h y l a m i n o m e t h y l -2 -g e r a n y l t h i o u r i d i n e (cmnm 5 ges 2 U). 2 Sometimes these modifications appear to be permanent additions to the RNA, whereas in other cases, modifications like N 6 -methyladenosine (m 6 A) or 4-thiouridine (s4U) are reversible and highly regulated. 3,4 Importantly, a single RNA molecule can harbor multiple modifications, resulting in numerous structures and functionalities. The implication here is that one gene (DNA sequence) can encode for myriad variations of mature RNA molecules based on these chemical decorations, the collection of which is termed the epitranscriptome. It is now appreciated that there is not one epitranscriptome as there is one genome, but instead a collection of epitranscriptomes depending on the cell type, environmental growth conditions, lifecycle stage, etc. 1 tRNAs harbor the largest number of modifications in both prokaryotes and eukaryotes with roughly 14 per molecule on average; 5 however, rRNA also require abundant modification for proper function. In eukaryotes, modifications are also regularly observed on mRNA and noncoding RNAs, whereas these modifications appear to be less common on the nonstructural prokaryotic RNAs. 5 We definitely have a long way to go to completely understand all of the RNA modifications within even the simplest of organisms, but the NASEM report encourages the first steps toward defining a single epitranscriptome in full and the long-term goal of being able to even assess more complex and dynamic epitranscriptomes.RNA modifications can currently be incompletely mapped using a variety of techniques, including mass spectrometry, next-generation RNA-sequencing technologies, and the emerging direct RNA sequencing approaches like the Oxford Nanopore Technologies (ONT) sequencing platform, among many others (Figure 1). 6 Each of these techniques has strengths and weaknesses, but none are presently able to sequence all RNA modifications on a single RNA to determine the full epitran...

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De novo rates of aTrypanosoma-resistant mutation in two human populations

Melamed,

Shemer,

Bolotin

et al. 2024

Preprint

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Until recently, mutation rates have only been measured as averages across many genomic positions. Recently, a method to measure mutation rates at the single-mutation resolution was applied to a narrow region in the human hemoglobin subunit beta (HBB) gene containing the site of the hemoglobin S (HbS) mutation as well as to a paralogous hemoglobin subunit delta (HBD) region, in sperm samples from sub-Saharan African and northern European donors. The HbS mutation, which protects against malaria while causing sickle-cell anemia in homozygotes originated de novo significantly more frequently in theHBBgene in Africans compared to the other three test cases combined (the EuropeanHBBgene and the European and AfricanHBDgene). Here, we apply this approach to the human apolipopro-tein L1 (APOL1) gene containing the site of the G1 1024A→G mutation, which protects against African sleeping sickness caused byTrypanosoma brucei gambiensewhile causing a substantially increased risk of chronic kidney disease (CKD) in homozygotes. We find that the 1024A→G mutation is the mutation of highest de novo origination rate and deviates most from the genome-wide average rate for its type (A→G) compared to all other observable mutations in the region, and that it originates de novo significantly more frequently in Africans than in Europeans—i.e., in the population where it is of adaptive significance. The results are inconsistent with the notion that the probability of a specific mutational event is independent of its value to the organism and underscore the importance of studying mutation rates at the single-mutation resolution.

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Evolutionary honing in and mutational replacement: how long-term directed mutational responses to specific environmental pressures are possible

Cited by 3 publications

References 155 publications

Mutation and evolution: Conceptual possibilities

Mutation and evolution: Conceptual possibilities

Past, Present, and Future of RNA Modifications in Infectious Disease Research

De novo rates of aTrypanosoma-resistant mutation in two human populations

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