Nonsynonymous substitution rate (Ka) is a relatively consistent parameter for defining fast-evolving and slow-evolving protein-coding genes

ABSTRACT Two chimpanzees, 1535 and 1536, became persistently infected following inoculation with RNA transcripts from cDNA clones of hepatitis C virus (HCV). Analysis of the HCV genomes from both animals showed an accumulation of amino acid substitutions over time. The appearance of substitutions in the envelope genes was associated with increased antienvelope antibody titers. However, extensive mutations were not incorporated into hypervariable region 1 (HVR1). A comparison of the nonsynonymous substitution rate/synonymous substitution rate was made at various time points to analyze selective pressure. The highest level of selective pressure occurred during the acute phase and decreased as the infection continued. The nonsynonymous substitution rate was initially higher than the synonymous substitution rate but decreased over time from 3.3 × 10−3 (chimpanzee 1535) and 3.2 × 10−3 (chimpanzee 1536) substitutions/site/year at week 26 to 1.4 × 10−3 (chimpanzee 1535) and 1.7 × 10−3 (chimpanzee 1536) at week 216, while the synonymous substitution rate remained steady at ∼1 × 10−3 substitutions/site/year. Analysis of PCR products using single-stranded conformational polymorphism indicated a low level of heterogeneity in the viral genome. The results of these studies confirm that the persistence of infection is not solely due to changes in HVR1 or heterogeneity and that the majority of variants observed in natural infections could not arise simply through mutation during the time period most humans and chimpanzees are observed. These data also indicate that immune pressure and selection continue throughout the chronic phase.

Download Full-text

Dissecting Fertility Functions of Drosophila Y Chromosome Genes with CRISPR

Genetics ◽

10.1534/genetics.120.302672 ◽

2020 ◽

Vol 214 (4) ◽

pp. 977-990 ◽

Cited By ~ 2

Author(s):

Yassi Hafezi ◽

Samantha R. Sruba ◽

Steven R. Tarrash ◽

Mariana F. Wolfner ◽

Andrew G. Clark

Keyword(s):

Male Fertility ◽

Nonsynonymous Substitution ◽

Wild Type ◽

Protein Coding ◽

Repeat Elements ◽

Protein Coding Genes ◽

The Third ◽

Link Type ◽

Complex Functions ◽

Lines Of Evidence

Gene-poor, repeat-rich regions of the genome are poorly understood and have been understudied due to technical challenges and the misconception that they are degenerating “junk.” Yet multiple lines of evidence indicate these regions may be an important source of variation that could drive adaptation and species divergence, particularly through regulation of fertility. The ∼40 Mb Y chromosome of Drosophila melanogaster contains only 16 known protein-coding genes, and is highly repetitive and entirely heterochromatic. Most of the genes originated from duplication of autosomal genes and have reduced nonsynonymous substitution rates, suggesting functional constraint. We devised a genetic strategy for recovering and retaining stocks with sterile Y-linked mutations and combined it with CRISPR to create mutants with deletions that disrupt three Y-linked genes. Two genes, PRY and FDY, had no previously identified functions. We found that PRY mutant males are subfertile, but FDY mutant males had no detectable fertility defects. FDY, the newest known gene on the Y chromosome, may have fertility effects that are conditional or too subtle to detect. The third gene, CCY, had been predicted but never formally shown to be required for male fertility. CRISPR targeting and RNA interference of CCY caused male sterility. Surprisingly, however, our CCY mutants were sterile even in the presence of an extra wild-type Y chromosome, suggesting that perturbation of the Y chromosome can lead to dominant sterility. Our approach provides an important step toward understanding the complex functions of the Y chromosome and parsing which functions are accomplished by genes vs. repeat elements.

Download Full-text

Two Korean Endemic Clematis Chloroplast Genomes: Inversion, Reposition, Expansion of the Inverted Repeat Region, Phylogenetic Analysis, and Nucleotide Substitution Rates

Plants ◽

10.3390/plants10020397 ◽

2021 ◽

Vol 10 (2) ◽

pp. 397

Author(s):

Kyoung Su Choi ◽

Young-Ho Ha ◽

Hee-Young Gil ◽

Kyung Choi ◽

Dong-Kap Kim ◽

...

Keyword(s):

Phylogenetic Analysis ◽

Inverted Repeat ◽

Nonsynonymous Substitution ◽

Single Copy ◽

Inverted Repeat Region ◽

Substitution Rates ◽

Protein Coding ◽

Protein Coding Genes ◽

Chloroplast Genomes ◽

Fundamental Information

Previous studies on the chloroplast genome in Clematis focused on the chloroplast structure within Anemoneae. The chloroplast genomes of Cleamtis were sequenced to provide information for studies on phylogeny and evolution. Two Korean endemic Clematis chloroplast genomes (Clematis brachyura and C. trichotoma) range from 159,170 to 159,532 bp, containing 134 identical genes. Comparing the coding and non-coding regions among 12 Clematis species revealed divergent sites, with carination occurring in the petD-rpoA region. Comparing other Clematis chloroplast genomes suggested that Clematis has two inversions (trnH-rps16 and rps4), reposition (trnL-ndhC), and inverted repeat (IR) region expansion. For phylogenetic analysis, 71 protein-coding genes were aligned from 36 Ranunculaceae chloroplast genomes. Anemoneae (Anemoclema, Pulsatilla, Anemone, and Clematis) clades were monophyletic and well-supported by the bootstrap value (100%). Based on 70 chloroplast protein-coding genes, we compared nonsynonymous (dN) and synonymous (dS) substitution rates among Clematis, Anemoneae (excluding Clematis), and other Ranunculaceae species. The average synonymoussubstitution rates (dS)of large single copy (LSC), small single copy (SSC), and IR genes in Anemoneae and Clematis were significantly higher than those of other Ranunculaceae species, but not the nonsynonymous substitution rates (dN). This study provides fundamental information on plastid genome evolution in the Ranunculaceae.

Download Full-text

Loss of the IR region in conifer plastomes: Changes in the selection pressure and substitution rate of protein‐coding genes

Ecology and Evolution ◽

10.1002/ece3.8499 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Jingyao Ping ◽

Jing Hao ◽

Jinye Li ◽

Yiqing Yang ◽

Yingjuan Su ◽

...

Keyword(s):

Substitution Rate ◽

Selection Pressure ◽

Protein Coding ◽

Protein Coding Genes

Download Full-text

Synonymous Site-to-Site Substitution Rate Variation Dramatically Inflates False Positive Rates of Selection Analyses: Ignore at Your Own Peril

Molecular Biology and Evolution ◽

10.1093/molbev/msaa037 ◽

2020 ◽

Vol 37 (8) ◽

pp. 2430-2439 ◽

Cited By ~ 11

Author(s):

Sadie R Wisotsky ◽

Sergei L Kosakovsky Pond ◽

Stephen D Shank ◽

Spencer V Muse

Keyword(s):

False Positive ◽

Substitution Rate ◽

Simulated Data ◽

Nonsynonymous Substitution ◽

Synonymous Substitution ◽

Rate Variation ◽

Nonsynonymous Substitution Rate ◽

Selection Testing ◽

The Impact ◽

Substitution Rate Variation

Abstract Most molecular evolutionary studies of natural selection maintain the decades-old assumption that synonymous substitution rate variation (SRV) across sites within genes occurs at levels that are either nonexistent or negligible. However, numerous studies challenge this assumption from a biological perspective and show that SRV is comparable in magnitude to that of nonsynonymous substitution rate variation. We evaluated the impact of this assumption on methods for inferring selection at the molecular level by incorporating SRV into an existing method (BUSTED) for detecting signatures of episodic diversifying selection in genes. Using simulated data we found that failing to account for even moderate levels of SRV in selection testing is likely to produce intolerably high false positive rates. To evaluate the effect of the SRV assumption on actual inferences we compared results of tests with and without the assumption in an empirical analysis of over 13,000 Euteleostomi (bony vertebrate) gene alignments from the Selectome database. This exercise reveals that close to 50% of positive results (i.e., evidence for selection) in empirical analyses disappear when SRV is modeled as part of the statistical analysis and are thus candidates for being false positives. The results from this work add to a growing literature establishing that tests of selection are much more sensitive to certain model assumptions than previously believed.

Download Full-text

Episodic evolution of prolactin receptor gene in mammals: coevolution with its ligand

Journal of Molecular Endocrinology ◽

10.1677/jme.1.01798 ◽

2005 ◽

Vol 35 (3) ◽

pp. 411-419 ◽

Cited By ~ 16

Author(s):

Ying Li ◽

Michael Wallis ◽

Ya-ping Zhang

Keyword(s):

Substitution Rate ◽

Transmembrane Domain ◽

Receptor Gene ◽

Prolactin Receptor ◽

Rapid Evolution ◽

Nonsynonymous Substitution ◽

Synonymous Substitution ◽

Episodic Evolution ◽

Nonsynonymous Substitution Rate ◽

Intracellular Domains

Divergence of proteins in signaling pathways requires ligand and receptor coevolution to maintain or improve binding affinity and/or specificity. In this paper we show a clear case of coevolution between the prolactin (PRL) gene and its receptor (prolactin receptor, PRLR) in mammals. First we observed episodic evolution of the extracellular and intracellular domains of the PRLR, which is closely consistent with that seen in PRL. Correlated evolution was demonstrated both between PRL and its receptor and between the two domains of the PRLR using Pearson’s correlation coefficient. On comparing the ratio of the nonsynonymous substitution rate to synonymous substitution rate (ω =dN/dS) for each branch of the star phylogeny of mammalian PRLRs, separately for the extracellular domain (ECD) and the transmembrane domain/intracellular domain (TMD/ICD), we observed a lower ω ratio for ECD than TMD/ICD along those branches leading to pig, dog and rabbit but a higher ratio for ECD than TMD/ICD on the branches leading to primates, rodents and ruminants, on which bursts of rapid evolution were observed. These observations can be best explained by coevolution between PRL and its receptor and between the two domains of the PRLR.

Download Full-text