2.1 细胞的结构 2.2 染色体 2.3 染色体的传递(细胞分裂) 第二章 遗传的物质基础 2.1 细胞的结构 2.2 染色体 2.3 染色体的传递(细胞分裂)

2.1 细胞的结构

细胞的结构(Structure of Cells) All start out life with: 细胞膜(Plasma membrane, encircling a region where DNA is stored) 细胞质(Cytoplasm) Two types: 原核(Prokaryotic) 真核(Eukaryotic)

真核细胞 (Eukaryotic Cells) 锥虫、披发虫等；纤毛虫纲包括喇叭虫、草履虫、四膜虫、钟形虫、栉毛虫等；肉足纲包括放射虫、衣壳虫、沙壳虫、太阳虫、变形虫、有孔虫等；孢子虫纲就一种典型的，是疟原虫。 真核细胞 (Eukaryotic Cells) 具细胞核和其他细胞器(Have a nucleus and other organelles) 真核生物(Eukaryotic organisms) 植物(Plants) 动物(Animals) 原生生物(Protistans)：所有不是动物、植物或真菌的真核生物，包括纤毛虫、鞭毛虫等（草履虫、锥虫、疟原虫） 真菌(Fungi)

动物细胞(Animal Cells) 中心体 Centrosome 质膜Plasma membrane 细胞核Nucleus 核糖体Ribosomes 内质网Endoplasmic reticulum 高尔基体Golgi body 小泡Vesicles 线粒体Mitochondria 溶酶体Lysosome 细胞骨架Cytoskeleton

植物细胞(Plant Cells) 细胞壁Cell wall 质膜Plasma membrane 中央液泡Central vacuole 叶绿体Chloroplast 质膜Plasma membrane 细胞核Nucleus 核糖体Ribosomes 内质网Endoplasmic reticulum 高尔基体Golgi body 小泡Vesicles 线粒体Mitochondria 溶酶体Lysosome 细胞骨架Cytoskeleton

细胞核(Nucleus)

G0和G1期染色体:染色质(Chromosomes at G1 phase: Chromatin) 8 G0和G1期染色体:染色质(Chromosomes at G1 phase: Chromatin) 30 nm G0和G1期细胞中染色体通常存在的状态(The “usual” state of chromosomes in G0 and G1 cells) Coding (blue) and non-coding strands (grey) of DNA 2 nm

S-G2期染色体:染色质(Chromosomes at S-G2 phase: Chromatin) 9 S-G2期染色体:染色质(Chromosomes at S-G2 phase: Chromatin) G2期细胞中染色体通常存在的状态(The “usual” state of chromosomes in G2 cells (after DNA replication) Special DNA binding proteins e.g. cohesins “Old” coding strand “New” coding strand 两个G1期染色质的并排排列，之间有cohesins蛋白连接

前期染色体(Chromosomes at prophase) 10 前期染色体(Chromosomes at prophase) Mitotic Chromosome “Old” coding strand “New” coding strand When cells entry mitosis: Chromatin condense together into a mitotic chromosome

The mechanism of chromosome condensation is 11 The mechanism of chromosome condensation is not completely understood but note… Condensin complex P Phosphorylation of histones & proteins in condensin complex

DNA package and chromosome condensation with cell cycle progression from G2 to metaphase

Human T-lymphocyte metaphase Karyotype 46, XY

中期染色体(Chromosomes at Metaphase) 5 um

着丝粒 Centromeres the largest constriction of the chromosome. 100,000s of 171 base pair repeat, called alpha satellite sequences Centromere associated proteins are bound: Kinetochore Site of attachment of spindle fibers

Centromere and Kinetochore

端粒 Telomeres At the tips of chromosomes: Protect Many repeats of the sequence TTAGGG Subtelomeres have more varied short repeats

人类全着丝粒探针 （pan-centromeric，Green) 和全端粒探针 （pan-telomeric， Red) 荧光原位杂交检测染色体的完整性 Human N-Tert1 cells have intact chromosomes detected by FISH using telomeric and centromeric probes Qinghua Shi unpublished These cells have intact chromosomes. All chromosomes have centromere, green spots. Each chromatid has telomeres at both ends, red spots. 人类全着丝粒探针 （pan-centromeric，Green) 和全端粒探针 （pan-telomeric， Red)

Tell me what I am ????? 染色体是一个物种区分于其他物种的最基本遗传特征

不同物种染色体数目不同 物种Species 二倍体 # 单倍体 # 牛Cattle 60 30 猪Swine 38 19 羊Sheep 54 27 马Horse 64 32 人Human 46 23 鸡Chicken 78 39 山羊Goat 60 30 驴Donkey 62 31 (The number of chromosomes in human cells were originally thought to number 48. It wasn’t until 1956 that the true number in humans was determined to be 46 and to consist of 23 pairs of homologous chromosomes.) 染色体最少的生物：一种蚂蚁（M. pilosula），单倍体细胞仅1条染色体 染色体最多的生物：？？？

染色体 The Chromosomes 染色体在体细胞中成对出现 Chromosomes occurs in pairs in every somatic cell except in the sperm and ovum. 一个物种的绝大多数（全部）体细胞，其染色体数目相同Chromosomes numbers are the same in vast majority (every) somatic cell for each species.

染色体 The Chromosomes 在二倍体细胞中含2条性染色体 There are 2 sex chromosomes included in the diploid number of the chromosomes. 除性染色体以外的染色体统称为常染色体 All of the other chromosomes are referred to as autosomes. 雌性哺乳类的2条性染色体相同 In mammals if the sex chromosomes are alike, XX it results in a female. 雄性哺乳类的2条性染色体不同 If the sex chromosomes are different, XY it results in a male.(例外：毛冠鹿)

染色体传递：细胞分裂 Chromosome transmitting: Cell Division Meiosis 减数分裂 Is the form of cell division which results reduce the chromosome number from the diploid # to the haploid #. Occurs only in the sex cells, generate sperm and egg. Mitosis 有丝分裂 Is the form of cell division which results in the formation of identical daughter cells, keeps the chromosome number constant. Tissue growth and repair. Occurs throughout the body except in the sex cells.

正常有丝分裂 绿色荧光蛋白（Green fluorescence protein, GFP）-组蛋白H2B融合基因，转入细胞中，使其表达 Shi & King, Nature 437:1038-1042, 2005 Abscission

细胞周期示意图 Cell Cycle Progression Shi, unpublished S G1 Checkpoint G2 Checkpoint G2 G1 Prophase A mechanism responds to chromosome missegregation? G2 checkpoint: Monitors DNA replication and damage repairing and blocks mitosis entry which allows cells more time to repair DNA damage or complete DNA synthesis. Spindle checkpoint: Monitors attachment & tension of kinetochore and blocks transition from metaphase to anaphase which allows cells more time to correct non-bipolar attachment of kinetiochores. Metaphase Spindle checkpoint Telophase 贝班 Anaphase

细胞周期 The Cell Cycle 是一个细胞从其形成到其分裂为2个细胞的一系列按序发生的事件 The cell cycle is an orderly sequence of events that occurs from the time when a cell is first formed until it divides into two new cells. Most of the cell cycle is spent in interphase（G1， S 和G2〕. Following interphase, the mitotic stage of cell division occurs. Division (前、中、后、末期和细胞质分裂〕

G2 During late interphase, before the start of mitosis, duplicated chromatin is condensing into chromosomes, and centrosomes have duplicated in preparation for mitosis.

Early Prophase. Chromosomes condense. Nuclear envelope disappears Early Prophase *Chromosomes condense *Nuclear envelope disappears *Centrioles move to opposite sides of the cell During early prophase, mitosis has begun. Duplicated chromosomes are now visible. Each chromosome is duplicated and composed of sister chromatids held together at a centromere. Centrosomes begin moving apart, the nuclear envelope is fragmenting, and the nucleolus will disappear.

Late Prophase Spindle forms and attaches to kinetochores on the chromosomes During late prophase, the spindle is forming and spindle fibers appear between the separating chromosomes. Centromeres attach to spindle fibers called centromeric (or kinteochore) fibers. The chromosomes have no particular orientation as yet.

Metaphase. Chromosomes lined up on equator of spindle Metaphase *Chromosomes lined up on equator of spindle *Centrioles at opposite ends of cell By the time of metaphase, the fully formed spindle consists of poles, asters, and fibers. The metaphase plate is a plane perpendicular to the axis of the spindle and equidistant from the poles. The chromosomes attached to the centromeric spindle fibers line up at the metaphase plate during metaphase. Polar spindle fibers reach beyond the metaphase plate and overlap.

Anaphase *Centromeres divide: each 2- chromatid chromosome becomes two 1-chromatid chromosomes *Chromosomes pulled to opposite poles by the spindle During anaphase, daughter chromosomes (each consisting of one chromatid) are moving toward the poles of the spindle. The daughter chromosomes have a centromere and a single chromatid. The movement of the daughter chromosomes occurs because the centromeric spindle fibers disassemble at the region of the centromere, pulling the daughter chromosomes toward the poles, and because the polar spindle fibers push the poles apart as they lengthen and slide past one another.

Telophase. Chromosomes decondense. Nuclear envelope reappears Telophase * Chromosomes decondense * Nuclear envelope reappears * Cytoplasm divided into 2 cells During telophase, the spindle disappears, and the nuclear envelopes begin to reform around daughter nuclei. Each 2n daughter nucleus contains the same numbers and kinds of chromosomes as the original 2n parental cell. Chromosomes become diffuse chromatin again, and a nucleolus appears in each daughter nucleus. At this point, cytokinesis is also nearly complete.

Cytokinesis in Animal Cells In animal cells, a cleavage furrow begins at the end of anaphase. A band of actin and myosin filaments, called the contractile ring, slowly forms a constriction between the two daughter cells. A narrow bridge between the two cells is apparent during telophase, then the contractile ring completes the division.

Cytokinesis in animal cells A single cell becomes two cells by a furrowing process. A contractile ring composed of actin filaments gradually gets smaller, and the cleavage furrow pinches the cell into two cells.

Mitosis in Detail During mitosis, the spindle distributes the chromosomes to each daughter cell. The spindle contains fibers made of microtubules that disassemble and assemble. Centrosomes, that duplicate and separate during interphase, organize the spindle. Centrosomes contain centrioles and asters. Mitosis has four phases: prophase, metaphase, anaphase, and telophase. Each centrosome contains a pair of barrel-shaped organelles called centrioles and an aster, which is an array of short microtubules that radiate from the centrosome. Plant cells lack centrioles; thus centrioles are not required for spindle formation.

Mitosis: Maintaining Chromosome Number Following DNA replication during interphase, each chromosome in the parental nucleus is duplicated and consists of two sister chromatids. During mitosis, the centromeres divide and the sister chromatids separate, becoming daughter chromosomes that move into the daughter nuclei. Therefore, daughter cells have the same number and kinds of chromosomes as the parental cell. In this figure, the blue chromosomes were inherited from one parent, and the red chromosomes were inherited from the other parent.

Meiosis: Halving chromosome number Following DNA replication, each chromosome is duplicated. During meiosis I, the homologous chromosomes pair during synapsis and then separate. During meiosis II, the centromeres divide and the sister chromatids separate, becoming daughter chromosomes that move into the daughter nuclei.

Meiosis: Two Divisions Two consecutive nuclear divisions Meiosis I Meiosis II DNA is NOT duplicated between divisions Four haploid nuclei are formed

Stages of Meiosis Meiosis I Meiosis II Prophase I Prophase II Metaphase I Anaphase I Telophase I Meiosis II Prophase II Metaphase II Anaphase II Telophase II

Chromosome behavior in meiosis I prophase

联合复合体（SC） SC:位于两条同源染色体之间，沿纵轴方向延伸； 两侧为侧生组分，宽约20-40nm； 侧生组分和中央组分之间有横向排列的纤维，大致成直角相连，称L-C纤细；SC主要由碱性蛋白组成

SYCP3: 示联会复合体侧轴；MLH1：示重组位点；CREST：示着丝粒 A 人精母细胞减数分裂I前期 SYCP3: 示联会复合体侧轴；MLH1：示重组位点；CREST：示着丝粒 发现了多种未见报道的减数分裂异常 Meiosis arrests at diplotene with various defects in synapsis. A-D Diplotene spermatocytes with various synapsis defects. E. Statistics of meiosis progression. F. Testicular section stained with H-E. (Red, green and blue marks SCP3, MLH1 foci and centromeres, respectively. n: the number of cells analyzed)

of chromosomes at metaphase I Meiosis I - Stages Crossing over Random alignment of chromosomes at metaphase I Homologues separate Prophase I Metaphase I Anaphase I Telophase I

Sister chromatids separate

精子发生 Spermatogenesis spermato- gonium (diploid male reproductive cell) primary spermatocyte (diploid) secondary spermatocytes (haploid) spermatids (haploid) Mitosis I, Cytoplasmic division Meiosis II, Cytoplasmic division Growth

卵子发生Oogenesis Growth 第一极体(n) first polar body (haploid) 三个极体(n) 3 polar bodies (haploid) 卵原细胞 (2n) oogonium (diploid reproductive cell) 初级卵母细胞 (2n) primary oocyte (diploid) 次级卵母细胞 (n) secondary oocyte (haploid) 卵子(n) ovum (haploid) Meiosis I, Cytoplasmic division Meiosis II, Cytoplasmic division Growth

人类生命周期 Life cycle of humans Meiosis in human males is a part of sperm production, and meiosis in human females is a part of egg production. When a haploid sperm fertilizes a haploid egg, the zygote is diploid, The zygote undergoes mitosis as it develops into a newborn child. Mitosis continues after birth until the individual reaches maturity; then the life cycle begins again.

受精 Fertilization 雌雄配子结合、细胞核融合 Male and female gametes unite and nuclei fuse 两个单倍体的配子融合形成二倍体的合子 Fusion of two haploid nuclei produces diploid nucleus in the zygote 配子融合是随机的 That two gametes unite is random 增加了子代的变异 Adds to variation among offspring

导致子代变异的因素 Factors Contributing to Variation Among Offspring 前期I同源染色体间的交换 （Crossing over during prophase I〕 中期I染色体在赤道板上的自由排列 （Random alignment of chromosomes at metaphase I〕 配子的自由组合 （Random combination of gametes at fertilization〕

有丝分裂和减数分裂比较 MITOSIS Occurs in most types of eukaryotic cells. MEIOSIS Occurs in formation of gametes in eukaryotic cells

有丝分裂和减数分裂比较 MITOSIS No pairing of Homologous chromosomes MEIOSIS Homologous chromosomes pair & synapsis; crossing over may occur

有丝分裂和减数分裂比较 MITOSIS Chromosome number is maintained. MEIOSIS Chromosome number is reduced from diploidy to haploidy.

有丝分裂和减数分裂比较 MITOSIS One division MEIOSIS Two divisions

有丝分裂和减数分裂比较 MITOSIS Two daughter cells are produced. MEIOSIS Four daughter cells are produced.

有丝分裂和减数分裂比较 MITOSIS Daughter cells are identical to each other and to parent cell MEIOSIS Daughter cells contain varying combinations of chromosomes

Mitosis & Meiosis Compared 有丝分裂和减数分裂比较 Mitosis Functions Asexual reproduction Growth, repair Occurs in somatic cells Produces clones Meiosis Function Sexual reproduction Occurs in germ cells Produces variable offspring

前期 (Prophase vs. Prophase I) 有丝分裂和减数分裂比较 有丝分裂前期 (Prophase, Mitosis) 同源染色体互不影响 (Homologous pairs do not interact with each other.) 减数分裂前期I (Prophase I, Meiosis) 同源染色体配对、联会、遗传物质交换（Homologous pairs become zippered together and crossing over occurs.)

分裂后期 减数分裂后期I (Anaphase I, Meiosis) 有丝分裂和减数分裂比较 减数分裂后期I (Anaphase I, Meiosis) 同源染色体分开(Homologous chromosomes are separated from each other.) 有丝分裂后期/减数分裂后期II (Anaphase/Anaphase II, Mitosis/Meiosis) 姐妹染色单体分开 (Sister chromatids of a chromosome are separated from each other)

分裂结果(Results of Mitosis and Meiosis) 有丝分裂和减数分裂比较 有丝分裂 (Mitosis) 2个二倍体细胞 (Two diploid cells produced) 2个子细胞均与亲代细胞相同 (Each identical to parent) 减数分裂 (Meiosis) 4个单倍体细胞 (Four haploid cells produced) 4个子细胞互不相同,且有别于亲代细胞 (Differ from parent and one another)

生命的细胞理论（1） 1) 每种生物都是由1个或多个细胞组成的 (Every organism is consisted of one or more cells) 2) 细胞是生命的最小单位(Cell is smallest unit of life) 3) 生命的延续是以单个细胞的生长和分裂为基础的(Continuity of life arises from growth and division of single cells)

生命的细胞理论（2） 4〕可独自生存或具此潜力 Can survive on its own or has potential to do so 5〕可进行高度有序的代谢 Is highly organized for metabolism 6〕可感受并对环境的变化作出反应 Senses and responds to environment 7〕具有增殖的潜力 Has potential to reproduce