# Week 12 From Dry to Wet, an Evolutionary Story. Evolution function analysis of DNA methyltransferase
<br>
<p align="justify"> Statement before class: All the contents here marked are belong to the course [<font color=orange>Bioinformatics: Introduction and Methods</font>](https://www.coursera.org/learn/bioinformatics-pku/home/welcome). If you like this high-quality course contents, please turn to the official course for more details. Here, i recored the knowledge learnt for convenience. If any copyright problem exist, please tell me, i’ll delete all immediately, Thanks!</p>
<br>
## Newly emerging genes are key sources of evolutionary novelty
<br>
Gene seq variation between duplicates will emerge as the evolution progresses. The seq variation will further lead to functional differentiation, and ultimately generate the new genes. => Sequence Divergebce ~ Funtional Novelty.

<br>
## 裴刚教授介绍甲基化酶
<br>
<p align="justify"> 细胞信号转导:接受外界信号并做出反应,传递到细胞内发生变化快速或长期的变化。<u>假说</u>:导致细胞功能的改变,即可能是通过表观遗传学方式造成的,基因组和序列不变的情况下,人体200多种细胞不同的表达,才有表观基因组/遗传组学。表观遗传学通过对细胞核内的DNA修饰(甲基化等)产生变化,对调控基因表达至关重要,那么甲基化过程中的重要部分就是**甲基化酶**。不同细胞内,不同生理病理中甲基化不同,是否与甲基化酶的结构(AA的组成,不同种属进化,生理病理的发生发展过程)有关,最终结构不同造成甲基化酶的功能不同。
<br>
蛋白质是组成的框架,是细胞膜的重要组成成分,还是作为信号转导的重要分子,细胞的新陈代谢能量利用相关,基因的转录翻译表达需要蛋白质。进化过程中重要有益突变保留,保守型分析发现保守型蛋白质具有重要功能,将特定AA突变,如果蛋白质功能丧失,那么这个AA是重要的,另外,蛋白质之间也是相互作用的,那么这些重要AA也是蛋白质件相互作用的重要关联,所以要研究一种蛋白功能,可以通过关联重要AA的另一种蛋白质分析,所以AA突变是研究蛋白质的重要途径。
<br>
生物信息学预测定位可能的,大概的研究方向,事半功倍。验证蛋白的方法,一是敲出的方法,二是过表达或抑制相应的表达,三是找到类似其他相近物种或等效基因进行研究。生信的应用:由于时间制约,验证理论思想需要生信建立理论系统。</p>
## Evolutionary Story Part2

<br>
DNA methylation level is decreased across whole genome. However, we can’t observe the similar phenomenon in DNMT3a knock-out mice. So what are the sequence changes leading to such functional differences?

<br>
Structural analysis suggested that the I -> N results in a tigher enzyme-DNA interacton.



The substitution from I -> N contributes to a stronger methylation activity of mammalian DNMT3b than DNMT3a and non-mammalian DNMT3b.

<br>
**Summary**
<br>
- Evolution-guided bioinformaticd analysis successfully identified interesting genes involved early development regulation showed clear functional novelty during evolution, and also provided strong hints for the key substitution, its biochemical effort, and the eventually functional significane.
- Key single substitution could result in significant functional novelty and help novel gene (re-) wired itself into exsiting circuits.
- An integrated, genome-scale bioinformatic analysis combined with targetted experimental assay is effective in studying complex biological system.
<br>
## Multiscale modelling today
- Complex processes in organic chemistry and biochemistry
- Heterogenerous catalysis
- Theoretical calculation of the spectrum


<br>
**<center>Correlated**
<br>
[Bioinformatics/ Introduction and Methos (Week 1 Bioinformatics Introduction)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethosweek1md)
[Bioinformatics/ Introduction and Methos (Week 2 Sequence Alignment)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethosweek2md)
[Bioinformatics/ Introduction and Methos (Week 3 Seq DB and BLAST Algorithnm)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethodsweek3md)
[Bioinformatics/ Introduction and Methos (Week 4 Markov Model)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethodsweek4md)
[Bioinformatics/ Introduction and Methos (Week 5 From Sequencing to NGS)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethodsweek5md)
[Bioinformatics/ Introduction and Methos (Week6 Variant Database)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethodsweek6md)
[Bioinformatics/ Introduction and Methos (Week7 Transcriptome Analysis, and RNA-Seq)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethodsweek7md)
[Bioinformatics/ Introduction and Methos (Week8 Prediction and Analysis of Noncoding RNA)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethodsweek8md)
[Bioinformatics/ Introduction and Methos (Week9 Ontology, Gene Ontology and KEGG Pathway Database)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethodsweek9md)
[Bioinformatics/ Introduction and Methos (Week 10 Bioinformatics Database and Resources)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethodsweek10md)
[Bioinformatics/ Introduction and Methos (Week 11 New Gene Evolution Detected by Genomic Computation: Basic Concepts and Examples)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethodsweek11md)
[Bioinformatics/ Introduction and Methos (Week 12 From Dry to Wet, an Evolutionary Story. Evolution function analysis of DNA methyltransferase)](https://www.haoxi.info/archives/bioinformaticsintroductionandmethodsweek12md)</center>

Bioinformatics: Introduction and Methods (Week 12)