Inheritance#

Prophase I#

1. chromatin coils up into chromosomes (condense)
2. centrosomes move towards opposite poles and then start to make microtubule spindle
3. Nuclear envelope and nucleolus disappear

上面发生的事情在mitosis中也会发生，但接下来发生的是属于prophase I的：

1. homologous chromosomes pair up to form bivalents. This process is called synapsis

   $$\text{homologous chromosomes} \xrightarrow{synapsis} \text{bivalents}$$

2. Crossing over might occur between non-sister chromatids of a pair of homologous chromosomes at chiasma, leading to exchange of genetic material and new combination of alleles

   Chiasma (plural. chiasmata) 交叉点

   corssing over这一步中交换了基因，会有新的allele产生，增加了genetic variation

3. Linkage groups are broken

   Linkage group - consists of genes that are located on the same chromosome and tend to be inherited together.

   The closer two genes are, the less likely the crossing over between them occurs.

Metaphase I#

1. Homologous chromosomes pairs (bivalents) line up across the equator of spindle
2. Each pair lines up independently of others
3. Independent assortment 自由组合/独立分配 of bivalents happens, resulting in $2^n$ chromosome / allele combinations ($n$ stands for the number of pairs of homologous chromosomes)

Independent assortment makes the gametes that are genetically unique. This is a result of the random alignment of bivalents on the equator of the spindle.

Total possible of chromosome combination: $2^n$

For example: human has 23 pairs chromosomes, so there are $2^{23} = 8324608$ different combinations.

Anaphase I#

1. Each pair of homologous chromosomes separates and moves to opposite poles, centromeres first, pulled by spindle microtubules
2. Centromere DO NOT divide
3. Spindle microtubules shorten

There are half the number of chromosomes go to the opposite ends, 2 haploid cells are formed.

这个地方会产生两个haploid的细胞，也就是说只有one complete set of chromosomes，但这个地方因为centromere没有分裂，所以每条chromosome上都有sister chromatids。

Telophase I#

1. Chromosomes uncoil into chromatin
2. Remains of spindle are breaking down
3. Nuclear envelope and nucleolus re-form

Meiosis II#

Meiosis II is just like mitosis, but no homologous chromosomes exist, and no DNA replication between meiosis I and meiosis II.

In prophase II of meiosis II:

1. Centrosomes replicate.

In metaphase II of meiosis II:

1. Chromosomes with sister chromatids line up across the equator of spindle.
2. Independent assortment of sister chromatids occurs.

In anaphase II of meiosis II:

1. Sister chromatids separate and move to opposite poles, centromeres first, pulled by spindle microtubules.
2. Centromeres DIVIDE.

In telophase II of meiosis II:

1. Four haploid nuclei are formed. 4 daughter cells are going to be formed.

Genetic Variation#

The genetic variation can comes from:

• meiosis stage

  • crossing over

    Crossing over begins from chiasmata formation, this is the exchange of genetic material between non-sister chromatids of homologous chromosomes, at meiosis I.

    And form new combination of alleles.

  • independent assortment

    Independent assortment会在meiosis中发生两次，分别在：

    • metaphase 1 - the random assortment of bivalents
    • metaphase 2 - the random assortment of chromatids

  • mutation - random change in base sequence of DNA, and form new alleles

• fertilisation stage

  • random mating
  • random fusion of gametes during random fertilisation

Inheritance#

Test cross - needed to determine the genotype of one organism showing dominant phenotype.

A large number of offspring gives a more accurate prediction.

Monohybrid inheritance - inheritance of one gene

1. Two true-breeding纯种的/pure-breeding /homozygous plants are crossed (cross=mate/breed).
2. The true-breeding parents are referred to as the P generation (parental generation).
3. The hybrid offspring are the F₁ generation (first filial generation, the word filial from the Latin word for “son”).
4. F₁ hybrids self-pollinate/cross-pollinate with other F₁ hybrids to produce an F₂ generation (second filial generation).

• All the F₁ individuals are heterozygous, called monohybrids.

• A cross between F₁ individuals is known as monohybrid cross. 这句话存疑，如果monohybrid是只考虑一个allele的话，就不可能是F₁这一代之间的杂交，P这一代的基因是GG和gg，所以F₁这一代的基因只可能是Gg。

• More broadly, monohybrid cross means a cross in which the inheritance of one gene is considered.

Alleles of one gene are separated along with the separation of homologous chromosomes in anaphase I. Each gamete inherits one allele of a gene.

Dihybrid inheritance & dihybrid cross

This involve the inheritance of 2 genes

• All the F₁ individuals are heterozygous, called dihybrids.
• A cross between F₁ individuals is known as dihybrid cross.
• More broadly, dihybrid cross means a cross in which the inheritance of 2 genes is considered.

During meiosis:

1. Alleles of one gene are separated along with the separation of homologous chromosomes in anaphase I.
2. Alleles of genes on non-homologous chromosomes combine.
3. Each gamete inherits one allele from each gene. 每个haploid继承母diploid上的一个allele

Sex-linkage

• Sex-linked gene: a gene located on one of the sex chromosomes and not on the other, usually on X chromosome
• Sex-linkage produces characteristics/features that are more common in one sex/gender than in the other

Red-green colour blindness

The gene is only located on X chromosome. The dominant allele $X^B$ codes for the normal vision, the recessive allele $X^b$ codes for the red-green colour blindness.

	genotype	phenotype
female	$X^B X^B$	woman with normal vision
	$X^B X^b$	woman with normal vision (who is a carrier) 携带者
	$X^b X^b$	woman with red–green colour blindness
male	$X^B Y$	man with normal vision
	$X^b Y$	man with red–green colour blindness

Haemophilia 血友病

The (F8) gene only on the X chromosome has 2 alleles：

1. The dominant allele codes for functional, normal factor VIII¹

2. The recessive allele cannot code for enough normal factor VIII, leading to lack of normal factor VIII.

• $X^F$ - normal blood clotting
• $X^f$ - haemophilia 血友病
• $Y$

Haemophilia: blood does not clot normally, and excessive bleeding can follow from even a small injury.

genotype	phenotype
$X^F X^F$	normal blood clotting
$X^F X^f$	normal blood clotting
$X^f X^f$	haemophilia
$X^F Y$	normal blood clotting
$X^f Y$	haemophilia

Autosomal Linkage

• Two genes on the same autosome (any chromosome that is not a sex chromosome) are said to be autosomally linked
• Autosomally linked genes tend to be inherited together and do not assort independently
• Each linkage group is bracketed in the genotype, e.g. $(AB)(ab)$

一般来说在有autosomal linkage的情况下，括号中的alleles是一起遗传的，把这个括号内的东西当成一个整体即可。

这边的例外是corssing over，发生crossing over时有小概率会互换括号行内的alleles。

左边的$(EA)(ex)$有一小部分变成了$(Ea)(eA)$

Crossing over between two gene loci is more likely to take place if the genes are further apart, because there is more length of chromosome between them that can cross over.

Epistasis 上位抑他性，上位效应

epistasis - the interaction of two genes at different loci; one gene affects the expression and phenotype of another

For example, in the inheritance of feather colour in chickens:

• Allele G is for coloured feathers
• Allele g is for white feathers.
• There is another gene F/f. When F is present, the feathers are white.

优先表达F，没有F时再看G和g。

Albinism 白化病#

异变基因：TYR gene

TYR gene (chromosome 11) has 2 alleles. The dominant allele is normal and can code for active tyrosinase. The mutant allele is recessive which leads to inactive tyrosinase.

Tyrosinase converts tyrosine into DOPA and then into dopaquinone. Then melanin is made in melanocytes 黑素细胞.

白化症患者没办法合成typosine，导致接下来的一串生产黑色素的过程都没办法发生。

Albinism only occurs in homozygous recessive people and affects hair, skin and iris.

Patients have pale hair and skin and pale blue or pink iris.

The condition is often accompanied by poor vision, rapid, jerky movements of the eyes and a tendency to avoid bright light.

NOTE

Explain how the presence of a mutant allele can result in albinism. [7]

• ref. to TYR gene ;
• normal gene product is tyrosinase ;
• tyrosine converted to, DOPA / dopaquinone ; ora
• melanin is made in melanocytes ;
• mutant allele is recessive ;
• tyrosinase, not produced / inactive ;
• affects, hair / skin / irises ;
• only in homozygous recessive people ;

Sickle Cell Anaemia 镰刀型细胞贫血病#

异变基因：HBB gene

• Hb^A = normal β-globin allele

• Hb^S = mutant β-globin allele

  The allele Hb^S has a base substitution and alters the tertiary structure of β-globin, and alters the quaternary structure of haemoglobin.

Mutated β-globin causes:

• Hb molecule to become less soluble in low pO₂
• Form long fibres
• Cells become crescent / sickle-shaped
• Carry less oxygen

异变后产生的别的特性：

• Sickled red blood cells break down faster → cause lack of RBCs

  更快分解

• Sickle cell crisis (RBC get stuck in capillaries and block blood flow) → Cause pain

  堵塞血管

• Sickle Cell Anaemia can give protection against malaria / Plasmodium infection

  提供针对于malaria的保护

NOTE

Outline the effects of the mutant sickle cell allele on the phenotype of a person with sickle cell anaemia. [9]

• homozygous for, mutant allele / Hb^S ; 写出变异的allele
• altered β polypeptide in haemoglobin ; 什么地方发生了改变
• haemoglobin / β-globin, less soluble ; 后果1
• in low(er) oxygen (concentration) ; 后果2
• (Hb) forms long fibres ; 形态变化
• red blood cells, sickle / form crescent shape ; 反映到红细胞上的形态变化
• (RBCs) carry less oxygen ; 红细胞的后果1
• sickle cell crisis: (RBCs) get stuck in capillaries, blocks blood flow and causes pain ;;;; 堵塞血管（价值四分）
• RBCs break down faster / lack of RBCs ; 更快分解
• protection against, malaria / Plasmodium infection ; 提供针对于正常血红细胞特异性感染疾病的保护

Haemophilia血友病#

异变基因：F8 gene on X chromosome

The sex-linked F8 gene only on the X chromosome, it has 2 alleles.

• The dominant allele X^F codes for functional, normal factor VIII

  Factor VIII - a protein necessary for blood clotting.

• The recessive allele X^f cannot code for normal factor VIII

The blood does not clot normally and excessive bleeding can follow from even a small injury.

由于haemophilia是由recessive sex-linked gene造成的，所以它的发生条件是：

• Female - X^fX^f
• Male - X^fY

Huntington’s disease亨廷顿病#

异变基因：HTT gene

The HTT gene (on chromosome 4) codes for the protein huntingtin. This gene contains repeated CAG triplets². When the number of CAG repeats is over 40, neurone development is abnormal.

• Dominant allele - faulty allele
• Recessive allele - normal allele

If a person has one dominant allele, the person develops Huntington’s disease.

When they get older, they will begin to lose ability to walk, talk and think.

Operon in Prokaryotic cells#

在prokaryotic cells中以lac operon为例:

The E. coli lac operon is an example of an inducible set of genes.

The responsibility of lac operon:

• transporting lactose in cell
• metabolizing (breakdown the lactose molecule into sugars)

lac → lactose

Operon - a cluster of functionally-related genes that are controlled by a shared operator and promoter, and transcribed together

lac operon是在DNA的一部分，它包括:

• structural genes: lacZ, lacY, lacA

• regulatory genes: promoter, operator

  Promoter和operator用于指示operon的起点和终点（tell the operon when to start and stop transcription）

  • Promoter - where RNA polymerase binds, allow the transcription to begin
  • Operator - where the repressor protein³ 阻遏蛋白 binds

其中的lacZYA genes负责生产用于transport和metabolise的蛋白质：

• lacZ - 生产β-galactosidase (lactase)，用于分解lactose，以及isomerise lactose to allolactose
• lacY - 生产β-galactosidase permease (lactose permease)，结合到CSM上成为channel protein，促使lactose进入细胞
• lacA - 生产β-galactoside transacetylase（这个部分的功能还不明确，算补充内容）

Repressor protein在glucose浓度高的时候bind于operator上，阻止RNA polymerase编译lacZYA genes。

当lactose的浓度显著高于glucose时，有一部分lactose会自然转换成lactose的isomer，allolactose，此时allolactose会bind到repressor protein上，使repressor protein改变形状并脱离operator，允许RNA polymerase编译lacZYA genes。

Constitutive protein (repressor protein)

• it is made all the time (produced continuously)
• concentration doesn’t vary

Inducible proteins (β-galactosidase, lactose permease, transacetylase)

• are not made all the time and only made when needed
• only made when the inducer lactose is present
• inducer causes the gene expression

如果没有repressor protein时，inducible proteins会一直产生，造成：

• waste of ATP and amino acid
• excess of protein
• decrease growth

NOTE

Describe the genetic control of protein production in a prokaryote using the lac operon. [7]

• the regulatory gene codes for repressor protein ;;
• (repressor protein) binds to operator ;

In presence of lactose

• lactose (allolactose) binds to repressor protein ;
• (repressor protein) changes shape and moves away from/no longer binds to, operator ;;

In absence of lactose

• repressor protein blocks promoter or promoter region now unblocked ;
• RNA polymerase cannot bind to promoter or RNA polymerase can now bind to promoter ;
• lacZYA genes cannot be transcribed / mRNA not synthesised or (named) gene now, transcribed / ‘switched on’ ;
• β-galactosidase and lactose permease cannot be synthesised or enzymes / named enzyme, can now be synthesised ;

Transcription Factors in Eukaryotic Cells#

WARNING

Eukaryotic cell中没有operon和operator，但是有promoter

In eukaryotic cells, RNA polymerase cannot bind to promoter directly. It needs the help of transcription factors.

Transcription factors are coded for by different regulatory genes.

How TFs carry out their role:

1. They are proteins that can bind to DNA.
2. They bind to promoter first, which then allows RNA polymerase to get attached to promoter/DNA.
3. They control transcription.

TF会先结合到promoter上，然后允许RNA polymerase附着到promoter上，三者结合在一起的整个东西被称为transcription initiation complex

Only after transcription factors are attached to the promoter does RNA polymerase II bind to it. The whole complex of transcription factors and RNA polymerase II bound to the promoter is called a transcription initiation complex.

NOTE

In eukaryotes, gene expression is controlled by transcription factors, coded for by regulatory genes.

Outline ways in which transcription factors carry out their role. [2]

any two from

1. proteins that bind to DNA ;
2. binds to the promoter ; A enhancers
3. control, gene expression / transcription / mRNA synthesis ;
4. allow attachment of RNA polymerase to DNA ;

这一部分还会关联到15单元中和植物生长（gibberellin）相关的知识：Control and Coordination - Gibberellin

NOTE

Gibberellin is a plant growth hormone that has a role in germination and in stem elongation.

Outline how gibberellin is involved in activating genes for stem elongation. [2]

any two from

1. idea that DELLA proteins prevent the activation of genes (for stem elongation) ;
2. gibberellin binds to receptors (on cell surface membrane) ;
3. causes breakdown of DELLA proteins ;
4. (so) transcription / gene expression / gene activation / mRNA synthesis, can occur ;
5. AVP ; e.g. ref. to transcription factors / PIF