From Trees to Traits: A Review of Advances in PhyloG2P Methods and Future Directions

The need for genome-wide statistical analysis methods with low error rates prompted the development of several new and updated phylogenetic methods that could be applied to genomic data.

“This need prompted the development of several new and updated phylogenetic methods that could be applied to this genomic data (Zou and Zhang 2015; Prudent et al. 2016; Rey et al. 2018; Hu et al. 2019; Kowalczyk et al. 2019; Treaster et al. 2021; Duchemin et al. 2022; Fukushima and Pollock 2023; Morel et al. 2024)”

• cites Zou and Zhang 2015 sourceNot checked — no full text of the source
• cites Prudent et al. 2016 sourceSupported
• cites Rey et al. 2018 sourceSupported

Several recent studies have applied multiple complementary PhyloG2P methods.

“This diversity has been actively embraced with several recent studies applying multiple complementary PhyloG2P methods (Eliason et al. 2023; Zhang et al. 2023; Eastment et al. 2024; Matsuda and Makino 2024)”

• cites Eliason et al. 2023 sourceSupported
• cites Zhang et al. 2023Not matched

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• cites Eastment et al. 2024 sourceSupported

Eastment et al. (2024) constructed a set of gene alignments from vertebrate genomes spanning over 400 million years of evolution that included 17 independent transitions to viviparity, a far larger number than earlier PhyloG2P studies.

“Eastment et al. constructed a set of gene alignments from vertebrate genomes spanning over 400 million years of evolution that included 17 independent transitions to viviparity, a far larger number than earlier PhyloG2P studies (Yusuf et al. 2023).”

• cites Eastment et al. 2024 sourcePartly supported

  The Background states that the study used vertebrate whole-genome data spanning more than 400 million years and accounting for 17 independent transitions to viviparity. But the Methods (Whole genome alignments) say the default alignment used for substitution-rate analysis accounted for 14 transitions; the 17-transition figure describes the broader dataset, not specifically its coding-gene alignments. (LLM, conf=0.84)

  Experimental — accuracy not yet measured
• cites Yusuf et al. 2023 sourceSupported

• AssumptionRests on an assumption: Viviparity has independently evolved many times in vertebrates such as squamate reptiles and fish, as well as once in mammals.
• AssumptionRests on an assumption: Few previous studies had used genome-wide approaches to explore whether the same genes were involved in independent transitions to viviparity across deep evolutionary time scales.

Gene ontology enrichment tests have often identified significant enrichment in functions related to the trait of interest.

“This verification can be done through gene ontology enrichment tests, which have often identified significant enrichment in functions related to the trait of interest (Chikina et al. 2016; Prudent et al. 2016; Nagy et al. 2017; Hu et al. 2019; Zhang et al. 2023; Redlich et al. 2024).”

• cites Chikina et al. 2016 sourceNot checked yet

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• cites Prudent et al. 2016 sourceSupported
• cites Nagy et al. 2017 sourceNot checked yet

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Expanding the phylogenetic breadth of a study may reveal additional biological variation, such as more phenotypic categories or intermediate phenotypes between presence and absence.

“For example, expanding the phylogenetic breadth of a study may reveal additional biological variation, such as more phenotypic categories or intermediate phenotypes between “presence” and “absence” (Redlich et al. 2024).”

• cites Redlich et al. 2024 sourceNot checked yet

The third group of PhyloG2P methods search for duplications or losses of genetic elements.

“The third group search for duplications or losses of genetic elements, encompassing a variety of genetic phenomena and phenotypic transitions associated with these changes.”

Identical substitutions at the same nucleotide position or amino acid may cause identical phenotypic changes, such as resistance to a common toxin.

“For instance, identical substitutions (or insertions/deletions) at the same nucleotide position or amino acid may cause identical phenotypic changes (Fig. 2a), such as resistances to a common toxin (Zhen et al. 2012).”

• cites Zhen et al. 2012 sourceNot checked yet

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Single-lineage PhyloG2P studies primarily deepen understanding of existing genotype-to-phenotype maps rather than developing novel ones.

“While successfully applied across a range of organisms, this PhyloG2P approach primarily deepens our understanding of existing genotype to phenotype maps, rather than developing novel ones.”

Changes in phenotype can be produced by duplication or loss of entire genes or noncoding regulatory elements.

“Changes in phenotype can also be produced by duplication or loss of entire genes or noncoding regulatory elements (Nagy et al. 2014, 2017).”

• cites Nagy et al. 2014, 2017Not matched

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Successfully identifying the genetic elements controlling traits with low pleiotropic constraint or high genetic redundancy from a PhyloG2P perspective would require prior knowledge of the genetic elements likely to be involved.

“Successfully identifying the genetic elements controlling such traits from a PhyloG2P perspective would require prior knowledge of the genetic elements likely to be involved.”

Changes in different sites within the same gene or regulatory element may produce a replicated phenotypic change.

“Changes in different sites within the same gene or regulatory element may also produce a replicated phenotypic change (Fig. 2b).”

• cites Sykes et al. 2022 sourceNot checked — no full text of the source

If a replicated change in phenotype has been achieved through changes in different genetic elements, PhyloG2P methods will fail to identify them unless considerable prior knowledge of the genetic elements involved can be leveraged to identify genetic replication at the network or pathway level.

“If a replicated change in phenotype has been achieved through changes in different genetic elements, then PhyloG2P methods will fail to identify them unless considerable prior knowledge of the genetic elements involved can be leveraged to identify genetic replication at the network or pathway level (Lamichhaney et al. 2019; Wheeler et al. 2022; Eastment et al. 2024; Shakya et al. 2025).”

• cites Lamichhaney et al. 2019 sourceNot checked yet

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• cites Wheeler et al. 2022 sourceNot checked yet

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• cites Eastment et al. 2024 sourceNot checked yet

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PhyloG2P methods have seen a surge of development and application over the past decade.

“PhyloG2P methods have seen a surge of development and application over the past decade.”

The multilineage PhyloG2P approach has the significant advantage of being able to identify novel genotype-to-phenotype associations without requiring detailed prior knowledge about the genetic elements involved.

“While this PhyloG2P approach has some limitations (discussed in the following subsections), it has the significant advantage of being able to identify novel genotype to phenotype associations without requiring detailed prior knowledge about the genetic elements involved.”

In single-lineage PhyloG2P studies, because most lineages have a substantial number of unique phenotypic features, identified genetic changes may be associated with any of these features rather than the phenotype of interest.

“However, since most lineages will have a substantial number of unique phenotypic features, the identified genetic changes may be associated with any of these features rather than the phenotype of interest”

• AssumptionRests on an assumption: Most lineages have a substantial number of unique phenotypic features.

As sequenced genomes rapidly increased in availability over the past 20 years, it became clear that there was a need for statistical analysis methods that could be applied genome-wide while maintaining low error rates.

“However, as sequenced genomes rapidly increased in availability over the past 20 years, it became clear that there was a need for statistical analysis methods that could be applied genome-wide while maintaining low error rates (Nagy et al. 2020).”

• cites Nagy et al. 2020 sourceNot checked yet

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Not all traits associated with marine mammals are exclusive to their marine adaptation.

“However, not all of the traits associated with marine mammals are exclusive to their marine adaptation.”

Evolved resistance to hypoxia is important to marine mammals because it facilitates extended dive duration.

“For example, the evolved resistance to the stress of hypoxia (low blood oxygen) is important to marine mammals, as it facilitates extended dive duration (Chikina et al. 2016).”

• cites Chikina et al. 2016 sourceNot checked yet

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If a genetic network controlling a trait has a low pleiotropic constraint or high genetic redundancy, genetic changes in different genetic pathways may create similar trait changes.

“Alternatively, if a genetic network controlling a trait has a low pleiotropic constraint, or high genetic redundancy, then genetic changes in different genetic pathways may create similar trait changes (Griesmann et al. 2018).”

• cites Griesmann et al. 2018 sourceNot checked yet

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Each PhyloG2P method uses a different statistical framework to determine the significance of identified correlations, based on its defined criteria for what constitutes replicated evolution.

“Each method uses a different statistical framework to determine the significance of identified correlations, based on their defined criteria for what constitutes replicated evolution.”

Presence/absence based PhyloG2P studies have successfully identified links between genetic elements and traits, especially in the context of trait loss.

“While presence/absence based studies have successfully identified links between genetic elements and traits (Chikina et al. 2016; Eliason et al. 2023; Zhang et al. 2023), especially in the context of trait loss (Prudent et al. 2016; Partha et al. 2019; Sackton et al. 2019)”

• cites Chikina et al. 2016 sourceNot checked yet

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• cites Eliason et al. 2023 sourceNot checked yet

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• cites Zhang et al. 2023Not matched

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As the CSUBST metric accounts for the expected number of both synonymous and nonsynonymous replicated substitutions, it is also robust to poor estimations of those expected numbers, which can pose a challenge for several other methods.

“Additionally, as the metric accounts for the expected number of both synonymous and nonsynonymous replicated substitutions, it is also robust to poor estimations of those expected numbers, which can pose a challenge for several of the other methods (Zou and Zhang 2015).”

• cites Zou and Zhang 2015 sourceNot checked — no full text of the source

Rates-based PhyloG2P methods search for genetic elements that evolve at different rates in foreground and background lineages.

“PhyloG2P methods based on changes in evolutionary rates search for genetic elements which evolve at different rates in foreground and background lineages.”

• cites Treaster et al. 2021 sourceNot checked yet

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Over time, the loss of selective pressure associated with trait loss will lead to the accumulation of various mutational changes across all impacted homologous genetic elements.

“While changes in a trait may be caused by a small number of genetic changes as described above, over time the loss of selective pressure associated with trait loss will lead to the accumulation of various mutational changes across all impacted homologous genetic elements.”

Genetic changes in different genetic networks may produce similar changes in a phenotype.

“Finally, genetic changes in different genetic networks, may produce similar changes in a phenotype (Fig. 2e).”

The first group of PhyloG2P methods search for replication at individual amino acid sites.

“The first group search for replication at individual amino acid sites.”

When a homologous trait has been lost multiple times in independent lineages, there is a relatively high chance of replicated increases in substitution rate, or reductions in copy number of genetic elements associated with the trait.

“As a result, when a homologous trait has been lost multiple times in independent lineages, there is a relatively high chance of replicated increases in substitution rate, or reductions in copy number of genetic elements associated with the trait (Hiller et al. 2012; Nagy et al. 2017; Zhang et al. 2023).”

• cites Hiller et al. 2012 sourceNot checked yet
• cites Nagy et al. 2017 sourceNot checked yet

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• cites Zhang et al. 2023Not matched

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Many early phylogenetic methods for identifying correlations between phenotypic and genotypic changes saw limited application, largely because of their poor statistical properties, such as simplistic null models leading to poor false positive rates.

“Many of these early methods saw limited application, largely because of their poor statistical properties, such as simplistic null models leading to poor false positive rates.”

The evolutionary perspective of PhyloG2P enables genotype to phenotype mapping in situations where typical population genetics approaches would be challenging, if not impossible to implement.

“This evolutionary perspective enables genotype to phenotype mapping in situations where typical population genetics approaches would be challenging, if not impossible to implement (Nagy et al. 2020; Smith et al. 2020).”

• cites Nagy et al. 2020 sourceNot checked yet

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• cites Smith et al. 2020 sourceNot checked — no full text of the source

PhyloG2P studies based on continuous traits can provide a more detailed understanding of what aspect of the trait the genetic elements control.

“PhyloG2P studies based on continuous traits can also provide a more detailed understanding of what aspect of the trait the genetic elements control (e.g. length, developmental timing, colour, etc) (Kowalczyk et al. 2020; Baker et al. 2021).”

• cites Kowalczyk et al. 2020 sourceNot checked yet

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• cites Baker et al. 2021 sourceNot checked yet

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Many available PhyloG2P methods depend on replicated evolution because independent evolutionary transitions provide the statistical power to distinguish phenotype-associated genetic changes from background genomic variation.

“However, many available PhyloG2P methods depend on replicated evolution, as these independent evolutionary transitions provide the statistical power to distinguish phenotype-associated genetic changes from background genomic variation.”

Utilizing evolutionary replication provides greater power to differentiate lineage-specific genetic changes from those that are shared between some or all of the lineages with the phenotype of interest.

“Utilizing evolutionary replication provides greater power to differentiate lineage-specific genetic changes from those that are shared between some or all of the lineages with the phenotype of interest.”

Lineages may achieve a similar phenotypic change through substitutions in, or duplications of, distinct genetic elements that are part of the same genetic pathway or network where changes have similar impacts on network function.

“These distinct genetic elements may be part of the same genetic pathway or network where changes have similar impacts on network function (Láruson et al. 2020; Shakya et al. 2025) (Fig. 2d).”

• cites Láruson et al. 2020 sourceNot checked — no full text of the source
• cites Shakya et al. 2025 sourceNot checked yet

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Utilizing replicated evolution provides a key advantage for discovering genotype-to-phenotype relationships even in genomic regions with no prior functional characterization.

“It has also been noted that utilizing replicated evolution provides a key advantage for discovering genotype to phenotype relationships, even in genomic regions with no prior functional characterization (Nagy et al. 2020).”

• cites Nagy et al. 2020 sourceNot checked yet

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Presence/absence based studies may oversimplify the biological processes under investigation, limiting the insights gained.

“they may also oversimplify the biological processes under investigation, limiting the insights gained (Lamichhaney et al. 2019).”

• cites Lamichhaney et al. 2019 sourceNot checked yet

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Replicated loss of homologous traits has been the focus of many PhyloG2P studies because it has a high chance of producing replicated genetic changes.

“Replicated loss of homologous traits has been the focus of many PhyloG2P studies, as it has a high chance of producing replicated genetic changes (Prudent et al. 2016; Sackton et al. 2019).”

• cites Prudent et al. 2016 sourceNot checked yet
• cites Sackton et al. 2019 sourceNot checked yet

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PhyloG2P methods that utilize replicated evolution may struggle when there is a low chance of any of the genetic changes being replicated across lineages.

“PhyloG2P methods that utilize replicated evolution may struggle in such cases, as there is a low chance of any of the genetic changes being replicated across lineages (Zou and Zhang 2015).”

• cites Zou and Zhang 2015 sourceNot checked — no full text of the source

Evolved resistance to hypoxia has also been essential for mammals that have transitioned to subterranean or high altitude environments.

“However, evolved resistance to hypoxia has also been essential for mammals that have transitioned to subterranean or high altitude environments, where oxygen availability is also limited (Wang et al. 2024) (Fig. 1).”

• cites Wang et al. 2024 sourceNot checked yet

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To fully characterize the genetic changes associated with evolutionary adaptations involving multiple traits, the traits may need to be investigated individually in addition to studying their collective replicated evolution.

“Therefore, to fully characterize the genetic changes associated with evolutionary adaptations involving multiple traits, such as those seen in marine mammals, the traits may need to be investigated individually in addition to studying their collective replicated evolution (Speed and Arbuckle 2017; Lamichhaney et al. 2019).”

• cites Speed and Arbuckle 2017Not matched

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• cites Lamichhaney et al. 2019 sourceNot checked yet

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The second group of PhyloG2P methods search for either individual or replicated changes in the rate of genetic evolution.

“The second group of approaches search for either individual or replicated changes in the rate of genetic evolution.”

Searching for genetic changes that are exclusively found in marine mammals may fail to detect some genetic elements underpinning hypoxia tolerance, because this adaptation is shared with other nonmarine lineages.

“As such, searching for genetic changes that are exclusively found in marine mammals may fail to detect some genetic elements underpinning hypoxia tolerance, as this adaptation is shared with other nonmarine lineages.”

Many PhyloG2P studies analyze traits as binary presence/absence patterns across lineages.

“Many PhyloG2P studies analyze traits as a binary presence/absence pattern across lineages, as they can be relatively simple to measure for a large number of individuals or species (Stefen et al. 2022).”

• cites Stefen et al. 2022 sourceNot checked yet

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The results of PhyloG2P studies will depend in part on where traits lie along a spectrum of complexity.

“We suggest that the results of PhyloG2P studies will depend in part on where traits lie along a spectrum of complexity.”

For genetic networks under a high degree of pleiotropic constraint, only a limited number of genetic changes may produce a particular trait change without causing deleterious changes in other traits controlled by the network.

“For genetic networks under a high degree of pleiotropic constraint, only a limited number of genetic changes may produce a particular trait change without causing deleterious changes in other traits controlled by the network (Stern 2013).”

• cites Stern 2013 sourceNot checked — no full text of the source

Measuring traits continuously rather than categorically can enhance statistical power.

“Similarly, measuring traits continuously rather than categorically can enhance statistical power, as for each lineage there is often more information than just the presence/absence of a trait.”

The likelihood of similar phenotypic changes being achieved through similar genetic changes in distinct lineages depends on the degree of pleiotropy and genetic redundancy in the genetic elements and networks that control the trait.

“The likelihood of similar phenotypic changes being achieved through similar genetic changes in distinct lineages depends on the degree of pleiotropy (Zhang 2023) (where a single genetic element can affect multiple traits) and genetic redundancy (Láruson et al. 2020) (where multiple different mutations can have similar impacts on a trait) in the genetic elements and networks that control the trait.”

• cites Zhang 2023Not matched

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• cites Láruson et al. 2020 sourceNot checked — no full text of the source

CSUBST uniquely examines replicated codon changes by independently analyzing synonymous and nonsynonymous substitutions.

“CSUBST uniquely examines replicated codon changes by independently analyzing synonymous and nonsynonymous substitutions.”

• cites Fukushima and Pollock 2023 sourceNot checked yet

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By accounting for synonymous substitutions, the CSUBST metric is robust to errors in topology which can confound other methods.

“By accounting for synonymous substitutions, this metric is robust to errors in topology which can confound the other methods described above (Mendes and Hahn 2016; Mendes et al. 2019).”

• cites Mendes and Hahn 2016 sourceNot checked yet
• cites Mendes et al. 2019 sourceNot checked yet

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For simple traits with easily quantifiable phenotypes and a simple genetic basis, PhyloG2P studies will have a chance to identify specific genotype-to-phenotype maps.

“On one end, we can conceptualize “simple” traits with both easily quantifiable phenotypes and a simple genetic basis. Here PhyloG2P studies will have a chance to identify specific genotype to phenotype maps (Lamichhaney et al. 2019; Nagy et al. 2020; Okuyama et al. 2025).”

• cites Lamichhaney et al. 2019 sourceNot checked yet

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• cites Nagy et al. 2020 sourceNot checked yet

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• cites Okuyama et al. 2025 sourceNot checked — no full text of the source

Other recent studies have used only a single PhyloG2P method.

“However, there have been other recent studies that only use a single PhyloG2P method (Xu et al. 2021; Sakamoto et al. 2024).”

• cites Xu et al. 2021Not matched

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• cites Sakamoto et al. 2024 sourceNot checked — no full text of the source

PhyloG2P studies have revealed genetic replication in noncoding regions when it was not found in coding regions.

“Similarly, PhyloG2P studies have revealed the presence of genetic replication in noncoding regions when it was not found in coding regions (Langer et al. 2018; Feigin et al. 2019; Thomas et al. 2024; Shakya et al. 2025).”

• cites Langer et al. 2018 sourceNot checked yet

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• cites Feigin et al. 2019 sourceNot checked yet

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• cites Thomas et al. 2024 sourceNot checked yet

PhyloG2P methods can also be used to complement other molecular and genetics approaches.

“PhyloG2P methods can also be used to compliment other molecular and genetics approaches.”

Rates-based methods can identify genetic elements under positive selection where multiple different mutations cause a similar phenotypic change, which single-site methods may miss.

“Additionally, in the context of replicated phenotypic transitions, evolutionary rates-based methods can identify genetic elements experiencing positive selection in which multiple different mutations could cause a similar change in phenotype (Fig. 2b), which may not be identified by methods based on replicated changes at single sites (Treaster et al. 2021).”

• cites Treaster et al. 2021 sourceNot checked yet

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Transgenic or knockout experiments are important because they provide evidence of causal relationships between a genetic element and a trait.

“These experiments are important, as they provide evidence of causal relationships between a genetic element and a trait (Losos 2011).”

• cites Losos 2011 sourceNot checked — no full text of the source

ESL uses binary encoding to enable joint analysis of any genetic feature, such as SNPs or presence/absence of a genetic element, as well as epigenetic or environmental variables.

“ESL uses binary encoding to enable joint analysis of any genetic feature, such as SNPs or presence/absence of a genetic element, as well as epigenetic or environmental variables.”

• cites Kumar and Sharma 2021 sourceNot checked yet

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There are many other epigenetic and transcriptomic features of genomes which can impact phenotypes, including DNA methylation, chromatin structure, structural rearrangements, and interactions between RNA, proteins, and their environment.

“These features include DNA methylation, chromatin structure, structural rearrangements (Vargas-Chavez et al. 2025), and the interactions between RNA, proteins, and their environment.”

• cites Vargas-Chavez et al. 2025 sourceNot checked yet

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These forms of variance are particularly important for the analysis of traits with continuous values, as allelic variation between individuals may contribute to significantly different values of the trait.

“These forms of variance are particularly important for the analysis of traits with continuous values, as allelic variation between individuals may contribute to significantly different values of the trait (such as height or lifespan).”

• AssumptionRests on an assumption: Allelic variation between individuals may contribute to significantly different values of continuous traits.

Another barrier is computational intensity.

“Another barrier is computational intensity.”

There is no single approach to determine the replicated genetic changes underlying phenotypic replication.

“The diversity of methods available means that there is no one single approach to determine the replicated genetic changes underlying phenotypic replication.”

Zhang et al. (2023) used PhyloG2P methods from all three categories (replicated amino acid substitutions, changes in evolutionary rates, and duplication/loss of genetic elements) to identify genetic replication across seven independent alpine transitions in the angiosperms.

“Zhang et al. (2023) used PhyloG2P methods from all three categories (replicated amino acid substitutions, changes in evolutionary rates, and duplication/loss of genetic elements) to identify genetic replication across seven independent alpine transitions in the angiosperms.”

• cites Zhang et al. 2023Not matched

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• AssumptionRests on an assumption: Many lineages of angiosperm plants have independently adapted to harsh alpine environments.

An important limitation of current PhyloG2P methods is that they rely on a single "representative" trait value and consensus genome for each lineage, which does not account for the phenotypic and genotypic variation within lineages.

“An important limitation of current PhyloG2P methods is that they rely on a single “representative” trait value and consensus genome for each lineage, which does not account for the phenotypic and genotypic variation within lineages.”

• AssumptionRests on an assumption: Trait values can vary widely within lineages, and this variance will likely not be consistent through time or between lineages.

It is likely that allelic variation within populations that have undergone replicated phenotypic evolution will show corresponding signs of adaptation in the genetic elements controlling the trait.

“It is also likely that allelic variation within populations that have undergone replicated phenotypic evolution will show corresponding signs of adaptation in the genetic elements controlling the trait (Barghi et al. 2020).”

• cites Barghi et al. 2020 sourceNot checked — no full text of the source

Okuyama et al.'s study highlights how PhyloG2P methods can complement other molecular genetics methods.

“This study highlights how PhyloG2P methods can compliment other molecular genetics methods.”

• cites Okuyama et al. 2025 sourceNot checked — no full text of the source

The subset of lineages in which Eastment et al. detected the replicated gene family contraction have all previously been identified as no longer producing yolk, including mammals.

“However, the subset of lineage that Eastment et al. (2024) detected the replicate gene family contraction in have all previously been identified as no longer producing yolk (including mammals).”

• cites Eastment et al. 2024 sourceNot checked yet

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There are potential barriers that can prevent the widespread application of PhyloG2P methods.

“There are potential barriers that can prevent the widespread application of PhyloG2P methods.”

Zhang et al. (2023)'s study demonstrates how different categories of PhyloG2P methods can identify distinct sets of genetic elements related to changes in component traits involved in complex phenotypic adaptations.

“Zhang et al. (2023)’s study demonstrates how the different categories of PhyloG2P methods can identify distinct sets of genetic elements related to changes in component traits involved in complex phenotypic adaptations.”

• cites Zhang et al. 2023Not matched

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Okuyama et al.'s analysis identified three substitutions within the gene that had occurred in all three independent transitions studied.

“Their analysis identified three substitutions within the gene that had occurred in all three independent transitions studied.”

• cites Okuyama et al. 2025 sourceNot checked — no full text of the source

ESL is orders of magnitude less computationally intensive than the PhyloG2P models discussed in this review.

“As well as its capacity to integrate a variety of variables relevant to phenotypic prediction, ESL is also orders of magnitude less computationally intensive than the PhyloG2P models discussed in this review.”

• cites Kumar and Sharma 2021 sourceNot checked yet

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Phenotypic replication can be caused by replicated changes at several genetic levels in both coding and noncoding genetic elements.

“Phenotypic replication can be caused by replicated changes at several genetic levels in both coding and noncoding genetic elements.”

One barrier is the accessibility of PhyloG2P methods from a technical perspective.

“One is the accessibility of PhyloG2P methods from a technical perspective.”

Relatively few applications of PhyloG2P methods have been followed up by transgenic or knockout experiments to verify the role of genetic elements identified in their analysis.

“However, relatively few applications of PhyloG2P methods have been followed up by transgenic or knockout experiments to verify the role of genetic elements identified in their analysis (Booker et al. 2016; Sackton et al. 2019; Xu et al. 2021; Okuyama et al. 2025).”

• cites Booker et al. 2016 sourceNot checked yet
• cites Sackton et al. 2019 sourceNot checked yet

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• cites Xu et al. 2021Not matched

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One shortcoming of using machine learning is that it does not explicitly model evolutionary processes, complicating the interpretation of the features it identifies.

“However, one shortcoming of using machine learning is that it does not explicitly model evolutionary processes, complicating the interpretation of the features it identifies.”

• AssumptionRests on an assumption: Machine learning does not explicitly model evolutionary processes.

Evolutionary rates analysis by Zhang et al. identified replicated changes in genes across different biological pathways.

“Evolutionary rates analysis identified replicated changes in genes across different biological pathways.”

• cites Zhang et al. 2023Not matched

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RERconverge requires branches to be assigned as foreground or background through ancestral state reconstruction, which can be challenging for many traits.

“The first issue is that RERconverge requires branches to be assigned as foreground or background through ancestral state reconstruction, which can be challenging for many traits”

• cites Treaster et al. 2021 sourceNot checked yet

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The δ statistic and RERconverge generally identify distinct sets of genetic elements for nonbinary categorical traits.

“Redlich et al. (2024) found that the δ statistic and RERconverge generally identified distinct sets of genetic elements, suggesting that further research into the impacts of these two approaches to modeling changes in evolutionary rate may be required.”

• cites Redlich et al. 2024 sourceNot checked yet

Okuyama et al.'s follow-up experiments manipulating those three sites confirmed they were necessary and sufficient to cause the phenotypic change.

“Their follow up experiments manipulating those three sites confirmed they were necessary and sufficient to cause the phenotypic change.”

• cites Okuyama et al. 2025 sourceNot checked — no full text of the source

Okuyama et al. (2025) used a range of transcriptomic, molecular, and transgenic approaches to understand the genetic mechanisms underlying replicated changes in floral scent compounds.

“Okuyama et al. (2025) used a range of transcriptomic, molecular, and transgenic approaches to understand the genetic mechanisms underlying replicated changes in floral scent compounds.”

• cites Okuyama et al. 2025 sourceNot checked — no full text of the source

Uncertainty in ancestral state reconstruction remains an important limitation for drawing conclusions from PhyloG2P analysis.

“However, uncertainty in ancestral state reconstruction still represents an important limitation, and it’s potential impacts should be considered carefully when drawing conclusions from PhyloG2P analysis.”

Zhang et al. identified accelerated evolution of genes relating to self-incompatibility using RERconverge.

“They also identified the accelerated evolution of genes relating to self-incompatibility (the inability to self fertilize) using RERconverge.”

• cites Zhang et al. 2023Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

High computational demands can limit the capacity for researchers to analyze genomic data.

“While high computational demands are common in genomic analysis, they can limit the capacity for researchers to analyze genomic data.”

• AssumptionRests on an assumption: High computational demands are common in genomic analysis.

Eastment et al. identified a contraction of a gene family related to yolk development in a subset of viviparous species.

“Notably, they identified a contraction of a gene family related to yolk development in a subset of viviparous species.”

• cites Eastment et al. 2024 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.

PhyloAcc's comparison of M1 over M2 prevents false positives from acceleration associated with a nonforeground trait, which other rates-based methods often do not account for.

“The second comparison with M2 prevents potential false positives resulting from acceleration associated with a nonforeground trait, which are often not accounted for in other rates-based methods.”

After identifying the responsible gene, Okuyama et al. used CSUBST to identify replicated amino acid substitutions in the foreground lineages.

“After identifying the responsible gene, they used CSUBST (Fukushima and Pollock 2023) to identify replicated amino acid substitutions in the foreground lineages.”

• cites Okuyama et al. 2025 sourceNot checked — no full text of the source
• cites Fukushima and Pollock 2023 sourceNot checked yet

  Checked before — its earlier verdict is held back until a new check runs.