21.6 Comparing genome sequences provides clues to evolution and development

## *ch 21 Genomes and their Evolution*

### 21.4

*21.4 Multicellular eukaryotes have much noncoding DNA and many multigene families*

### 21.5

*21.5 Duplication, rearrangement, and mutation of DNA contribute to genome evolution*

### 21.6

***21.6 Comparing genome sequences provides clues to evolution and development***

## 前情提要

In the last 25 years, we have seen rapid advances in

* genome sequencing and data collection 基因定序資料蒐集
* new techniques for assessing gene activity across the whole genome 基因活動，橫跨整個基因體
* Refined approaches for understanding how genes and their products work together in complex systems. 更好的管道了解基因體在複雜系統下的作用。

comparative studies

* genome sequences from different species
* embryonic development in different species

### 比較遠親

Genes highly conserved—in distantly related species

* Bacteria
* Archaea
* Eukaryotes

support the theory that they are the fundamental domains of life

#### 模式生物的研究

research on model organisms

Very ancient genes can still be surprisingly similar in disparate species.古老的相似基因還留在早已分家的個體裡。

Researchers have deduced the functions of the human genes by studying their yeast counterparts. 比較酵母菌上人類的相對基因就可以研究基因突變所造成的疾病。

### 比較近親

Using the human genome sequence as a guide, researchers were able to quickly sequence the chimpanzee

genome. 研究人類也可以順便研究猩猩的基因(因為很類似)

Most genomes are assembled individually, as has been done recently for the bonobo and gorilla genomes. (Along with chimpanzees, bonobos are the other African ape species that are the closest living relatives to humans.)

比較物種間的相異基因

An exciting application of this type of analysis is seen as researchers compare the human genome with the genomes of the chimpanzee, mouse, rat, and other mammals.

Identifying the genes shared by all of these species but not by nonmammals should give clues about what it takes to make a mammal, while finding the genes shared by chimpanzees and humans but not by rodents will tell us something about primates 靈長目.比較不同層次的基因可以定義不同層次的基因相似度，例如哺乳綱或是靈長目。

* human and chimpanzee genomes have diverged only about **6** million years ago.
* Considering single nucleotide substitutions, the two genomes differ by only **1.2%**. 只有比對單一核甘酸序列的話猩猩與人類只有1.2%的差異性。
* longer stretches of DNA, **2.7%** difference due to insertions or deletions of larger regions in the genome of one or the other species. 有2.7%是因為插入或移除核甘酸。

> many of the insertions were duplications or other repetitive DNA.
>
>

* **a third** of the human duplications are not present in the chimpanzee genome, and some of these duplications contain regions associated with human diseases.三分之一的人類重複基因(見21.4)沒有出現在猩猩身上。這些重複基因造成一些人類疾病。

1. There are more Aluelements in the human genome.人類有很多alu元件。
2. Chimpanzee genome contains many copies of a retroviral provirus not present in humans.猩猩有很多反轉錄原病毒的基因片段。

> All of these observations provide clues to the forces that might have swept the two genomes along different paths, but we don’t have a complete picture yet.
>
>

不管是bonobo還是chimpanzee都有各自有和人類比較相似的基因，由此可描繪出演化的歷史。

To discover the basis for the phenotypic differences between chimpanzees and humans, biologists are studying specific genes and types of genes that differ between the two species and comparing them with their counterparts in other mammals.研究基本表現型相異的地方，比較猩猩和人類相異的基因，再比對哺乳類動物的。

人類某些基因比猩猩或小鼠演化的還快。

這些基因包含:

* malaria 瘧疾
* tuberculosis 結核
* 大腦大小
* transcription factor 轉錄因子(演化最快，因為調控基因的轉錄，指揮整個基因表現)

#### FOXP2

A gene in development of speech and language in humans and of vocalization 發聲 in other vertebrates 脊椎動物。

1. 在小鼠干擾FOXP2的結果包含brain anatomy 腦部解剖學 and vocalization 發聲。
	1. 腦部細胞的排列會混亂
	2. 干擾2個染色體比1個更難發聲
2. 在人類干擾FOXP2影響說話、語言能力。
3. 在zebra finch 斑胸草雀 和 canary 金絲雀 身上影響學習唱歌

把兩個人類和猩猩不同的人類胺基酸序列裝進小鼠的基因，小鼠的腦部迴路會稍微改變成人類大腦的語言區。

#### 尼安德塔

人類和他們雜交過30000年前，他們其實是可以說話的(依據FOXP2)

依據人類某些位置上基因導致的疾病，我們會回去研究小鼠上的相同片段。

我們也需要研究生命樹上被忽略的分支。

## 一個種族裡的比較

human species is so short—probably about **200,000** years

Much of our diversity seems to be in the form of single nucleotide polymorphisms (SNPs)單一核甘酸多形性

* 100-300個核甘酸就有1個SNP

In the course of this search, they have also found other variations—including chromosomal regions with inversions,deletions, and duplications.

**CNVs - DNA序列中的拷貝數變異 = STR短縱列重複序列 的數量多樣性**

* Being duplicated or deleted inconsistently within the population.
* 40 people found more than 8,000 CNVs involving 13% of the genes in the genome.(人數多寡不影響CNV的變異程度)
* CNVs are more likely to have phenotypic consequences and to play a role in complex diseases and disorders.

從研究非洲的一個古老的部落的STR多樣性，牠們的族群很小，但是和歐洲人與亞洲人的序列比較，可以研究人類遷徙的路線圖。