Neutral Theory and Phenotypic Evolution

Zhang, Jianzhi

doi:10.1093/molbev/msy065

Cited by 42 publications

(30 citation statements)

References 37 publications

(36 reference statements)

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“…However, cases where functions of different APA isoforms have been clearly demonstrated are still rare compared to the ubiquity of the phenomenon. It has therefore been proposed that most observed APA is noise (“error hypothesis”; Xu & Zhang, ) and that APA divergence between species is largely neutral or slightly deleterious (“neutral theory”; Zhang, ). Here, we address these issues in an F1 mouse model by investigating APA diversity within each tissue, APA differences between tissues, and cis ‐regulatory divergence between Mus musculus (C57BL/6J) and its sister species Mus spretus (SPRET/EiJ).…”

Section: Discussionmentioning

confidence: 99%

“…The authors support this hypothesis by showing that in general, lower gene expression levels correlate with higher APA diversity within and between tissues. In extension of Kimura's neutral theory of molecular evolution (Kimura, , ), Zhang also suggests that differences between species in gene regulatory phenotypes like APA are largely non‐adaptive, as only a small fraction of these will affect higher‐level phenotypes and organismal fitness (Zhang, ).…”

Section: Introductionmentioning

confidence: 99%

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Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation

Schaefke

Zou

et al. 2020

Molecular Systems Biology

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Alternative polyadenylation (APA) is a major layer of gene regulation. However, it has recently been argued that most APA represents molecular noise. To clarify their functional relevance and evolution, we quantified allele-specific APA patterns in multiple tissues from an F1 hybrid mouse. We found a clearly negative correlation between gene expression and APA diversity for the 2,866 genes (24.9%) with a dominant polyadenylation site (PAS) usage above or equal to 90%, suggesting that their other PASs represent molecular errors. Among the remaining genes with multiple PASs, 3,971 genes (34.5%) express two or more isoforms with potentially functional importance. Interestingly, the genes with potentially functional minor PASs specific to neuronal tissues often express two APA isoforms with distinct subcellular localizations. Furthermore, our analysis of cis-APA divergence shows its pattern across tissues is distinct from that of gene expression. Finally, we demonstrate that the relative usage of alternative PASs is not only affected by their cis-regulatory elements, but also by potential coupling between transcriptional and APA regulation as well as competition kinetics between alternative sites.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation

Schaefke

Zou

et al. 2020

Molecular Systems Biology

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“…If there is selection for more or less variation, then this may shift the selection pressure from particular phenotypes to particular regions of LALI-space. A rich literature of theory can be applied to such phenotypic landscapes, such as the neutral theory of Kimura [50,51], survival of the flattest [52] and arrival of the frequent [53].…”

Section: The L→ P Maps Provides An Important Metric For Interpretingmentioning

confidence: 99%

Isolating and Quantifying the Role of Developmental Noise in Generating Phenotypic Variation

Kiskowski

Glimm

Moreno

et al. 2018

Preprint

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Phenotypic variation in organisms is typically attributed to genotypic variation, environmental variation, and their interaction. Developmental noise, which arises from stochasticity in cellular and molecular processes occurring during development when genotype and environment are fixed, also contributes to phenotypic variation. The potential influence of developmental noise is likely underestimated in studies of phenotypic variation due to intrinsic mechanisms within organisms that stabilize phenotypes and decrease variation. Since we are just beginning to appreciate the extent to which phenotypic variation due to stochasticity is potentially adaptive, the contribution of developmental noise to phenotypic variation must be separated and measured to fully understand its role in evolution. Here, we show that phenotypic variation due to genotype and environment, versus the contribution of developmental noise, can be distinguished for leopard gecko (Eublepharis macularius) head color patterns using mathematical simulations that model the role of random variation (corresponding to developmental noise) in patterning. Specifically, we modified the parameters of simulations corresponding to genetic and environmental variation to generate the full range of phenotypic variation in color pattern seen on the heads of eight leopard geckos. We observed that over the range of these parameters, the component of variation due to genotype and environment exceeds that due to developmental noise in the studied gecko cohort. However, the effect of developmental noise on patterning is also substantial. This approach can be applied to any regular morphological trait that results from self-organized processes such as reaction-diffusion mechanisms, including the frequently found striped and spotted patterns of animal pigmentation patterning, patterning of bones in vertebrate limbs, body segmentation in segmented animals. Our approach addresses one of the major goals of evolutionary biology: to define the role of stochasticity in shaping phenotypic variation.

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“…A neutral mutation can change composition of genome but not affect superposition of networks. As result, evolution rate of genome is higher than observed at the organism level 42 .…”

Section: Biological Superposition As a Principle To Understand Adaptimentioning

confidence: 73%

Can random mutation explain phenotypic variability?

Trejo

2018

Preprint

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The epigenome regulates the gene expression of all differentiated cells and indicates which specific genes must be transcribed. It is argued that the expression factors that act on specific genes of the somatic cell involved in a behavior also act on the transcription of the same genes in the most undifferentiated cells of the germ line. It is proposed how a probabilistic view of the random mutation can explain the evolution of the phenotypes and integrate all the evidence pointing to a joint evolution with the environment.

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Neutral Theory and Phenotypic Evolution

Cited by 42 publications

References 37 publications

Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation

Pan‐tissue analysis of allelic alternative polyadenylation suggests widespread functional regulation

Isolating and Quantifying the Role of Developmental Noise in Generating Phenotypic Variation

Can random mutation explain phenotypic variability?

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