A novel approach to molecular evolution study

China has a large land area with highly diverse topography, climate and vegetation, and animal resources and is ranked eighth in the world and first in the Northern Hemisphere on richness of biodiversity. Even though little work on molecular evolution had been reported a decade ago, studies on both the evolution of macromolecules and the molecular phylogeny have become active in China in recent years. This review highlights some of the interesting and important developments in molecular evolution study in China. Chinese scientists have made significant contribution on the methods inferring phylogeny and biogeography of animals and plants in East Asia using molecular data. Studies on population and conservation genetics of animals and plants, such as Golden monkey and Chinese sturgeon, provided useful information for conserving the endangered species. East and South Asia has been demonstrated to be one of the centres of domestication. Origin and evolution of genes and gene families have been explored, which shed new insight on the genetic mechanism of adaptation. In the genomic era, Chinese researchers also made a transition from single-gene to a genomic investigation approach. Considering the fact that amazing progress has been made in the past few years, and more and more talented young scientists are entering field, the future of molecular evolution study in China holds much promise.

Download Full-text

Pattern recognition of sequence similarities in globular proteins by Fourier analysis: A novel approach to molecular evolution

Journal of Molecular Evolution ◽

10.1007/bf02101001 ◽

1986 ◽

Vol 23 (1) ◽

pp. 80-87 ◽

Cited By ~ 7

Author(s):

A. M. Liquori ◽

A. Ripamonti ◽

C. Sadun ◽

S. Ottani ◽

D. Braga

Keyword(s):

Pattern Recognition ◽

Molecular Evolution ◽

Fourier Analysis ◽

Globular Proteins ◽

Novel Approach ◽

Sequence Similarities

Download Full-text

A machine-learning-guided mutagenesis platform for accelerated discovery of novel functional proteins

10.1101/282996 ◽

2018 ◽

Author(s):

Yutaka Saito ◽

Misaki Oikawa ◽

Hikaru Nakazawa ◽

Teppei Niide ◽

Tomoshi Kameda ◽

...

Keyword(s):

Machine Learning ◽

Molecular Evolution ◽

Fluorescent Protein ◽

Yellow Fluorescent Protein ◽

Screening Experiments ◽

Novel Approach ◽

Machine Learning Model ◽

High Enrichment ◽

Green Fluorescent ◽

Protein Variants

AbstractMolecular evolution based on mutagenesis is widely used in protein engineering. However, optimal proteins are often difficult to obtain due to a large sequence space that requires high costs for screening experiments. Here, we propose a novel approach that combines molecular evolution with machine learning. In this approach, we conduct two rounds of mutagenesis where an initial library of protein variants is used to train a machine-learning model to guide mutagenesis for the second-round library. This enables to prepare a small library suited for screening experiments with high enrichment of functional proteins. We demonstrated a proof-of-concept of our approach by altering the reference green fluorescent protein (GFP) so that its fluorescence is changed to yellow while improving its fluorescence intensity. Using 155 and 78 variants for the initial and the second-round libraries, respectively, we successfully obtained a number of proteins showing yellow fluorescence, 12 of which had better fluorescence performance than the reference yellow fluorescent protein (YFP). These results show the potential of our approach as a powerful platform for accelerated discovery of functional proteins.

Download Full-text

Molecular evolution of a cytochrome P450 for the synthesis of potential antidepressant (2R,6R)-hydroxynorketamine

Chemical Communications ◽

10.1039/d0cc06729f ◽

2021 ◽

Author(s):

Ansgar Bokel ◽

Michael C. Hutter ◽

Vlada B. Urlacher

Keyword(s):

Cytochrome P450 ◽

Molecular Evolution ◽

Cytochrome P450 Monooxygenase ◽

P450 Monooxygenase ◽

Effective Synthesis

Engineered cytochrome P450 monooxygenase CYP154E1 enables the effective synthesis of the potential antidepressant (2R,6R)-hydroxynorketamine via N-demethylation and regio- and stereoselective hydroxylation of (R)-ketamine.

Download Full-text

Copper-dependent ATP7B up-regulation drives the resistance of TMEM16A-overexpressing head-and-neck cancer models to platinum toxicity

Biochemical Journal ◽

10.1042/bcj20190591 ◽

2019 ◽

Vol 476 (24) ◽

pp. 3705-3719 ◽

Cited By ~ 2

Author(s):

Avani Vyas ◽

Umamaheswar Duvvuri ◽

Kirill Kiselyov

Keyword(s):

Oxidative Stress ◽

Head And Neck ◽

Transcriptional Activation ◽

Platinum Resistance ◽

Mrna Levels ◽

Strong Positive Correlation ◽

Platinum Compounds ◽

Copper Chelation ◽

Novel Approach ◽

Cancer Models

Platinum-containing drugs such as cisplatin and carboplatin are routinely used for the treatment of many solid tumors including squamous cell carcinoma of the head and neck (SCCHN). However, SCCHN resistance to platinum compounds is well documented. The resistance to platinum has been linked to the activity of divalent transporter ATP7B, which pumps platinum from the cytoplasm into lysosomes, decreasing its concentration in the cytoplasm. Several cancer models show increased expression of ATP7B; however, the reason for such an increase is not known. Here we show a strong positive correlation between mRNA levels of TMEM16A and ATP7B in human SCCHN tumors. TMEM16A overexpression and depletion in SCCHN cell lines caused parallel changes in the ATP7B mRNA levels. The ATP7B increase in TMEM16A-overexpressing cells was reversed by suppression of NADPH oxidase 2 (NOX2), by the antioxidant N-Acetyl-Cysteine (NAC) and by copper chelation using cuprizone and bathocuproine sulphonate (BCS). Pretreatment with either chelator significantly increased cisplatin's sensitivity, particularly in the context of TMEM16A overexpression. We propose that increased oxidative stress in TMEM16A-overexpressing cells liberates the chelated copper in the cytoplasm, leading to the transcriptional activation of ATP7B expression. This, in turn, decreases the efficacy of platinum compounds by promoting their vesicular sequestration. We think that such a new explanation of the mechanism of SCCHN tumors’ platinum resistance identifies novel approach to treating these tumors.

Download Full-text

Collecting Words: A Clinical Example of a Morphology-Focused Orthographic Intervention

Language Speech and Hearing Services in Schools ◽

10.1044/2020_lshss-19-00050 ◽

2020 ◽

Vol 51 (3) ◽

pp. 544-560 ◽

Cited By ~ 3

Author(s):

Kimberly A. Murphy ◽

Emily A. Diehm

Keyword(s):

Written Language ◽

Morphological Knowledge ◽

English Orthography ◽

Word Level ◽

Novel Approach ◽

Language Pathology ◽

The One ◽

Critical Intervention ◽

Reading And Spelling ◽

Reading And Spelling Difficulties

Purpose Morphological interventions promote gains in morphological knowledge and in other oral and written language skills (e.g., phonological awareness, vocabulary, reading, and spelling), yet we have a limited understanding of critical intervention features. In this clinical focus article, we describe a relatively novel approach to teaching morphology that considers its role as the key organizing principle of English orthography. We also present a clinical example of such an intervention delivered during a summer camp at a university speech and hearing clinic. Method Graduate speech-language pathology students provided a 6-week morphology-focused orthographic intervention to children in first through fourth grade ( n = 10) who demonstrated word-level reading and spelling difficulties. The intervention focused children's attention on morphological families, teaching how morphology is interrelated with phonology and etymology in English orthography. Results Comparing pre- and posttest scores, children demonstrated improvement in reading and/or spelling abilities, with the largest gains observed in spelling affixes within polymorphemic words. Children and their caregivers reacted positively to the intervention. Therefore, data from the camp offer preliminary support for teaching morphology within the context of written words, and the intervention appears to be a feasible approach for simultaneously increasing morphological knowledge, reading, and spelling. Conclusion Children with word-level reading and spelling difficulties may benefit from a morphology-focused orthographic intervention, such as the one described here. Research on the approach is warranted, and clinicians are encouraged to explore its possible effectiveness in their practice. Supplemental Material https://doi.org/10.23641/asha.12290687

Download Full-text