Molecule and DNA structure and replication

gene

is the sequence of DNA that encodes a specific protein or functional RNA.

allele

A variant form of a gene that arises by mutation and is found at the same place on a chromosome.

genome:

The complete set of genetic material in an organism, including all of its genes and non-coding sequences.

genotype

a gene that is individual inherited

phenotype

visible trait resulting from the interaction of genetics and environment.

gene expression

• turning on “gene: to produce DNA and protein

• turning the genotype and phenotypes

• follow the dogma central ( DNA —> RNA—> protein through transcription and translation) - can produce both non-coding and coding

protein expression 

• type and how much protein is made

• although protein expression  carry DNA molecules information, proteins ultimately determine the phenotypes because it control most of the reaction 

• type

  • enzyme: catylyze synthesis and tranformation of all biomolecules

  • Structural protein: maintain the cell strucutre

  • Signalling protein: hormones and receptors

Phenotypic variation cause

• different alles ( slight variation in gene sequence result in change of amino acid sequence of protein) 

• different regulation of gene and protein expression 

• unique alles and different regulation result in countless phenotype possibilities

• similar alleles and gene regulation lead to more similar  protein expression and phenotypes

Gregor mendel

The father of modern genetics, known for his pioneering work on the inheritance of traits in pea plants, establishing the laws of inheritance.

• how trait from generation can pass down to the next generation

• heritable traits result in mixing of “ praticular factor”

• each factor has two copies, one from each parent

Chromosome theory of inheritance

• individual has two copies of each chromosome

• similar or homologous chromosome seperate independently during meiosis to 4 daughter cell, contain half of no of chromosomes

gametes

have one copy of each chromosome

zygotes: 

the random combination of 2 gametesto form a diploid cell.

3 experiment lead to DNA as genetic material

Griffith:

• molecules that act as transforming principle

Avery:

• identify DNA is the transforming principle

Hershey:

• evidence show the DNA is genetic material

Griffith experiment

• Streptococcus pneumonia: bacteria pathogent that cause pneumonia

  • S ( smooth ) strain:virulent because it has polysaccharides capsule to protein it from immune system

  • R ( rough) is benign

• Step :

  • 4 experiment that when heat-killed the s- cell and input R cell then mice died,

  • state: molecules ( transforming principles) were released when s-cell were heat-killed, release the molecules would transform r cell into s-cell

• transfromation is permanent and hertable ( all progeny contains)

Avery, macleod, MacCarthy

• systematically eliminate each molecules until the tranformation of R-cell into S-cell stop, the molecules is missing is determined as the transforming molecules 

• step: kill and lyse the cell, remove sugar and lipid, input R-cell

  • Protase —> dies

  • Rnase: die

  • Dnase _ alive

• —> DNA is transformation molecules

Hershey and Chase

• use bacteriophage: ( virus that infect bacteria) and its E.coli host to show that DNA is the trnasforming principles

• attachmnet the virus gentic matral is injected into the host and phage remain outside—> hudenred progeny are amde, then burst

• DNA use phosphorus and protein use sulfur

  • 2 population of virus

    • radioactive phorphorys in it DNA

    • radioactive sulfur in protein

• Experiment 1: 35s was not found in E.coli and newly made phage

• Ex 2: 32p is found in both E.coli host and newly made phage

Molecular structure of DNA 

1. pentose sugrar 

• deoxyribose which is deoxyribonucleic acid in DNA

• ribose which is ribonucleic acid in RNA

—> difference: chemical group attach to 2’ carbond

2. nitrogenous base

• purine ( double rings): guanin and adenin

• pyrimidine (single rings): cytosine, thymine, and uracil

—> attach to the 1’ carbon

3. phosphate group (P04)

Nitrogenous base difference

• guanine having both NH2 and double bond to oxygen

• adenine only have NH2

• cytosine only have one double bond to 0 but thymine and uracile has two. and thymine. has methyl group while uracile does not

Nucleoside

A nucleoside consists of a nitrogenous base covalently bonded to a pentose sugar, without a phosphate group. It serves as the building block for nucleotides, which include a phosphate group

• deoxygadenosine

• deozyguanosine

• deoxythymidine

• deoxycytidine.

Nucleotides

• Nucleotides are the basic building blocks of nucleic acids, consisting of a nitrogenous base, a pentose sugar, and one or more phosphate groups. They are essential for DNA and RNA synthesis.

• phosphate is bind to 5’ carbon of sugar

DNA structure

• nuclotide monomer polymerize via phosohodiester bond, covalent bond between phosphate group and 2 pentose sugar at 5’ and 3’ carbon

• polynucleotide has polarity 5’ end ( bond to the phosphate) and 3’ end bond tothe hyroxyl group taht the end

• type of nucleic acid depend on sugar type

• DNA has negative charge

Erwin Chargaff:

rule

• percentage of A = % T

• %C=%G

Other conclusion

• % pyring = % pyrimidine 

• A+t not equal C+G 

• A,C,T,G is not presnet in equal amount 

ROsalind Franklin

• DNA is cylindrical and 2 nm diameter 

• 0.34 nm periodicity which base pair is on top one another 

• X-ray difraction indicates that DNA is helixcal structure 

• she does not have definitive model 

• Her colledgue gives image to waston 

Watson and Crick

• two stands DNA is spiral as double helix bout a common axis

• Two stand run atiparallel

• Purine on one strand is paired with teh pyrimidine base on other ( based on chaff rule)

• The exterior of backbone is hydrophylic and interior of hydophobic and connected two stand by hydrogen bonds

DNA double helix

• base pairing complementary so one stand can be used to specify another stand 

• base pair stacked lying perpedicular to the axis contribue to teh stabiluty 

• hydrogen bond between based to keep 2 stand intact

DNA model - watson anc crick

complementary base pairing allow the parental strand act as tempate to synthesize new strand

• parental strand can unwide by breaking hydrogen bonds

• semi-consevative replication where the double helix will contain one stand form parente and new synthized stand

DNA organize in eularyotic cell

• DNA molecules is multiple linear chromosomes that exclosed in nucleus

• 3.2 base pair in DNA molecule s

• 2 meter pack in cell 250000 smaller

• to keep DNA organized and regulate gene expression, it condensed into chromatin

• DNA double helix is first wrapped 1.65 around histone octamer to form the nucleosome

• Histone is basic with positve charge to neutralize the negative change on DNA.

Specific structure in eykaryotic nucleus

• DNA molecules is repeating series of nuclesomes called 10nm chromatin fibre

• then histone cause it to coild futher into 30nm chromatin fibre ( solenoid)

• chromatin is normal stant

• unwind when replication and transciption

• condensed into chromosomes in meiosis and mitosis

Histone and DNA around

• Nucleosome is histone octamer with around 147 bp of DNA wrapped around it, forming the fundamental unit of chromatin structure.

• ach full turn contain aourn 6 nuclesomes 

• Histne H1 binds linker DNA and nucleosomes to form solenoid. 

Euchromatin

• region where less DNA compaction and genes are actively expressed 

Heterochromatin

• high DNA compaction, is silensed

  • Costitutive heterochromatin is always high DNA compacted, such as cetromere and sub-telomerics

  • Facultative heterochromatin can become decompacted depending on the cell type and developmental stage, allowing for regulation of gene expression.

Chromosome organization 

• chromosome compacts  DNA fully 

• chromosomal structure can protect DNA from daamge

• easily speratate and transmitted to daughter cell during cell division 

component of chromosome

• orgin of replicaiton: DNA sequence along chromosome which initiate Dna replication

• centromere: dna squence required for correct segregation by directing formation of kinetochore protein where miotic spinddle attaches

• telomere: DNa sequence at the end of chromosomes that protect DNA fromdegrattion and allow proper DNA replocation of the chromsomes end

Majority of ploidy

• diploid, 2 set of chromosomes one from each parent

• haploid: sexually repproductve cell

• polyploidy: more that a pair of each chromosome such as protist and flowering plant

DNA organization is prokaryotics cell

• it is double-stand ciruclar small DNA 

• have other DNA called plasmid

• DNA delocalized in cytosol 

• Prokaryotic DNA does not need same level of compaction as eukaryotic DNA due to lack of histones and does not form complex structures such as nucleosomes.

• Histone like protein or nucleioid associated protein

• each cell havae mutiple type of plasmid and copies

• plasmid carries a gene non-essential to life, but give some advatanges insome environmental

  • metabolism

  • competition

  • antibiotic resistance

Potential model of DNA replication

• semiconservative replication: daughter stand remain one from parent and one new stand

• consevative DNA: after replication: all new daughter strand pair up

• Dispersive DNA replication: mixture of both parent and newly synthesized NDA 

Evidence of Semincoservative DNA replication: Meselson and Stahl

trackin by nitrogen isotopes

Step

• N14 is lighter with abudant nitrogen isotope

• N15 have additional neutron so heavier

• E.col grew in medium contains only N15, result in neucleotide contains 100% N15, in nitrgoenous bases

• DNA is isolated and centrifuged in CsCl, and position based on density

• transfer E.coli into medium contain N14, result nucleotide with 100% of N14 in nitrogenous base

• sample in single round of replication then second round