Sequence Divergence, Functional Constraint, and Selection in Protein Evolution

Fay, Justin C.; Wu, Chung‐I

doi:10.1146/annurev.genom.4.020303.162528

Cited by 254 publications

(171 citation statements)

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“…Such variation in rate (heterotachy) may point to lineage-specific positive selection or relaxation of evolutionary constraints 77 . We developed a statistical method similar to the recently described Gene Set Enrichment Analysis (GSEA) [78][79][80] to detect evidence of heterotachy for sets of functionally related genes (see Supplementary Information).…”

Section: Genesmentioning

confidence: 99%

Genome sequence, comparative analysis and haplotype structure of the domestic dog

Lindblad‐Toh¹,

Wade²,

Mikkelsen³

et al. 2005

Nature

2,218

2,079

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Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.

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Section: Genesmentioning

confidence: 99%

Genome sequence, comparative analysis and haplotype structure of the domestic dog

Lindblad‐Toh¹,

Wade²,

Mikkelsen³

et al. 2005

Nature

2,218

2,079

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“…measured by the K a /K s ratio) than species like mouse or Drosophila (for review, see Fay and Wu 2003). Currently, there is currently no comparative analysis on miRNA emergence between closely related species that have disparate Ne's (which should be reflected in their genome-wide K a /K s ratio).…”

Section: Mirnas and Expression Buffering-the Emergence Of New Mirnasmentioning

confidence: 99%

Evolution under canalization and the dual roles of microRNAs—A hypothesis

Wu¹,

Shen²,

Tang³

2009

Genome Res.

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146

167

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Canalization refers to the process by which phenotypes are stabilized within species. Evolution by natural selection can proceed efficiently only when phenotypes are canalized. The existence and identity of canalizing genes have thus been an important, but controversial topic. Recent evidence has increasingly hinted that microRNAs may be involved in canalizing gene expression. Their paradoxical properties (e.g., strongly conserved but functionally dispensable) suggest unconventional regulatory roles. We synthesized published and unpublished results and hypothesize that miRNAs may have dual functions-in gene expression tuning and in expression buffering. In tuning, miRNAs modify the mean expression level of their targets, but in buffering they merely reduce the variance around a preset mean. In light of the constant emergence of new miRNAs, we further discuss the relative importance of these two functions in evolution.Living organisms process as much information and execute as many instructions as any high-power computers normally do. The difference is that living organisms carry out the tasks under extremely variable environments, whereas no computers are made to withstand even moderate fluctuations in voltage input. Living things must be able to dampen variable inputs (in nutrition, temperature, humidity, genetic background, etc.) to achieve the remarkable stability in the output (development, physiological responses, gene expression, etc.). This phenomenon is the essence of biological homeostasis.Darwin's The Origin of Species (Darwin 1859), on the other hand, is about evolutionary changes. On the surface, evolutionary changes and phenotypic stability may seem like antithetical concepts, but in the language of genetics they are really two sides of the same issue. Evolution by natural selection can proceed only when biological systems are reasonably stable. Imagine a system in which phenotypic manifestation is highly variable. In it natural selection cannot easily distinguish one genotype from another and would have low efficacy. The original nongenetic version of the Darwinian theory encountered many difficulties. One of them was the blending of genetic materials, potentially leading to the homogenization of phenotypes. The other resulted from the ignorance of the difference between genotype and phenotype and the puzzle over the existence of phenotypic variation. Fisher (1930) pointed out that, in Darwin's thinking, phenotypic variation should have been purged by natural selection-only the fittest should have remained.The relationship between evolution and biological homeostasis can best be expressed in quantitative genetic terms. Let V g and V e denote phenotypic variance due to genotypic and environmental effect, respectively. V g 3 e is the interactive term between gene and environment. The total phenotypic variance, V t , can be expressed as follows:For simplicity, we assume no dominance here, but the general principle is the same in more complex systems. Any mechanism of biological homeostasis should redu...

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“…When comparing observed data to neutral expectations, too little variation implies that purifying selection has constrained changes in gene expression, whereas too much variation implies that selection has either maintained variation within a population or driven divergence between species. Tests of neutrality based on the rate of expression changes are analogous to the tests of neutrality based on the rate of synonymous and nonsynonymous substitutions in protein coding sequences (Fay and Wu, 2003).…”

Section: Rates Testsmentioning

confidence: 99%

Evaluating the role of natural selection in the evolution of gene regulation

Fay¹,

2007

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Surveys of gene expression reveal extensive variability both within and between a wide range of species. Compelling cases have been made for adaptive changes in gene regulation, but the proportion of expression divergence attributable to natural selection remains unclear. Distinguishing adaptive changes driven by positive selection from neutral divergence resulting from mutation and genetic drift is critical for understanding the evolution of gene expression. Here, we review the various methods that have been used to test for signs of selection in genomic expression data. We also discuss properties of regulatory systems relevant to neutral models of gene expression. Despite some potential caveats, published studies provide considerable evidence for adaptive changes in gene expression. Future challenges for studies of regulatory evolution will be to quantify the frequency of adaptive changes, identify the genetic basis of expression divergence and associate changes in gene expression with specific organismal phenotypes.

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Sequence Divergence, Functional Constraint, and Selection in Protein Evolution

Cited by 254 publications

References 100 publications

Genome sequence, comparative analysis and haplotype structure of the domestic dog

Genome sequence, comparative analysis and haplotype structure of the domestic dog

Evolution under canalization and the dual roles of microRNAs—A hypothesis

Evaluating the role of natural selection in the evolution of gene regulation

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