Download The origin of life molecules Nucleotide（核苷酸）

The origin of life molecules
• CH4, H2,NH3,H2O, CO2
Molecular Biology and Public Health
（分子生物学与公共卫生）
-----------basic molecules of life
（生命的基本分子）
Nucleobases（核酸碱基） and
Nucleosides（核苷）
• Lightning
• HCN (氰氢酸)
• Urea (尿素)
• Adenine (腺嘌呤)
Nucleotide（核苷酸）
• 5 bases: The primary nucleobases are cytosine(胞嘧啶，DNA
and RNA), guanine(鸟嘌呤，DNA and RNA), adenine(腺嘌呤，
DNA and RNA), thymine (胸腺嘧啶，DNA) and uracil (尿嘧啶，
RNA), abbreviated as C, G, A, T, and U, respectively.
• Ribose （核糖）
• Phosphate groups （磷酸基团）
• Nucleoside（核苷酸）, oligonucleotides （寡核苷酸）
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Amino acids（氨基酸）
• Amino acids are biologically important organic compounds made
from amine (-NH2) and carboxylic acid (-COOH) functional groups,
along with a side-chain specific to each amino acid.
• The key elements of an amino acid are carbon, hydrogen, oxygen,
and nitrogen, though other elements are found in the side-chains of
certain amino acids.
• 甘氨酸（Glycine）、丙氨酸（Alanine）、缬氨酸（Valine）、亮氨酸
（Leucine）、异亮氨酸（Isoleucine）、苯丙氨酸（Phenylalanine）、
色氨酸（Tryptophan）、酪氨酸（Tyrosine）、天冬氨酸（Aspartic
acid）、组氨酸（Histidine）、天冬酰胺（Asparagine）、谷氨酸
（Glutamic acid）、赖氨酸（Lysine）、谷氨酰胺（Glutamine）、甲
硫氨酸（Methionine）、精氨酸（Arginine）、丝氨酸（Serine）、苏
氨酸（Threonine）、半胱氨酸（Cysteine）、脯氨酸（Proline）等
• 9 of the 20 standard amino acids are called "essential" for humans
because they cannot be created from other compounds by the
human body, and so must be taken in as food.
Peptides（肽） and Proteins（蛋白质）
• Peptides are short chains
of amino acid monomers
linked by peptide (amide)
bonds.
• Proteins consist of one or more polypeptides arranged in
a biologically functional way, often bound to ligands such
as coenzymes and cofactors, or to another protein or
other macromolecule (DNA, RNA, etc.), or to complex
macromolecular assemblies.
• Peptides are distinguished from proteins on the basis of
size, and as a benchmark can be understood to contain
approximately 50 amino acids or less.
Two basic characters of life:
metabolism（代谢） and
reproduction （生殖/繁殖）
• Metabolism is the set of life-sustaining chemical
transformations within the cells of living
organisms.
• Reproduction (or procreation) is the biological
process by which new "offspring" individual
organisms are produced from their "parents".
Reproduction is a fundamental feature of all
known life; each individual organism exists as
the result of reproduction. The known methods
of reproduction are broadly grouped into two
main types: sexual and asexual.
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RNA（核糖核酸）
• Ribonucleic acid (RNA) is a ubiquitous
family of large biological molecules that
perform multiple vital roles in the coding,
decoding, regulation, and expression of
genes.
• mRNA, rRNA, tRNA, tmRNA, microRNA,
antisense RNA, Ribozyme
mRNA
• Messenger RNA (mRNA) is a large family of
RNA molecules that convey genetic
information from DNA to the ribosome, where
they specify the amino acid sequence of the
protein products of gene expression.
• Following transcription of mRNA by RNA
polymerase, the mRNA is translated into a
polymer of amino acids: a protein, as
summarized in the central dogma of molecular
biology.
rRNA
• Ribosomal ribonucleic acid (rRNA) is the RNA component of the
ribosome, and is essential for protein synthesis in all living organisms.
• Ribosomes contain two major rRNAs and 50 or more proteins. The
LSU and SSU rRNAs are found within the large and small ribosomal
subunits, respectively. The LSU rRNA acts as a ribozyme, helping
catalyze peptide bond formation.
Large subunit (rRNAs)
Small subunit
(rRNA)
prokaryotic 70S
50S (5S: 120 nt, 23S: 2906 nt)
30S (16S: 1542 nt)
eukaryotic
60S (5S: 121 nt, 5.8S: 156 nt, 28S: 5070 nt)
40S (18S: 1869 nt)
Type
The "life cycle" of an mRNA in a eukaryotic cell. RNA is transcribed in the
nucleus; processed, it is transported to the cytoplasm and translated by the
ribosome. Finally, the mRNA is degraded.
Size
80S
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tRNA
• A Transfer RNA (tRNA) is an adaptor molecule
composed of RNA, typically 73 to 94 nucleotides in
length, that serves as the physical link between the
nucleotide sequence of nucleic acids (DNA and RNA)
and the amino acid sequence of proteins.
• It does this by carrying an amino acid to the protein
synthetic machinery of a cell (ribosome) as directed by a
three-nucleotide sequence (codon) in a messenger RNA
(mRNA). As such, tRNAs are a necessary component of
protein translation, the biological synthesis of new
proteins according to the genetic code.
The interaction of tRNA and mRNA in protein synthesis.
tmRNA
• Transfer-messenger RNA (abbreviated
tmRNA, also known as 10Sa RNA and by
its genetic name SsrA) is a bacterial RNA
molecule with dual tRNA-like and
messenger RNA-like properties. The
tmRNA forms a ribonucleoprotein complex
(tmRNP) together with Small Protein B
(SmpB), Elongation Factor Tu (EF-Tu),
and ribosomal protein S1.
tmRNA combines features of tRNA and mRNA.
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microRNA
• A microRNA (abbr. miRNA) is a small non-coding RNA
molecule (ca. 22 nucleotides) found in plants and
animals, which functions in transcriptional and posttranscriptional regulation of gene expression.
• Encoded by eukaryotic nuclear DNA, miRNAs function
via base-pairing with complementary sequences within
mRNA molecules, usually resulting in gene silencing via
translational repression or target degradation.
trans-Translation stages A through F. A ribosome with its RNA binding sites, designated
E, P, and A, is stuck near the 3' end of a broken mRNA. The tmRNP binds to the A-site,
allowing the ribosome to switch templates from the broken message onto the open
reading frame of the tmRNA via the resume codon (blue GCA). Regular translation
eventually resumes. Upon reaching the tmRNA stop codon (red UAA), a hybrid protein
with a proteolysis tag (green beads) is released.
• The human genome may encode over 1000 miRNAs,
which may target about 60% of mammalian genes and
are abundant in many human cell types.
antisense RNA
• Antisense RNA (asRNA) is a single-stranded
RNA that is complementary to a messenger
RNA (mRNA) strand transcribed within a cell.
Some authors have used the term micRNA
(mRNA-interfering complementary RNA) to refer
to these RNAs but it is not widely used.
miRNA Processing Pathway. (1) miRNAs are expressed in the nucleus as
parts of long primary miRNA transcripts (Pri-miRNA) that have 5’ caps and 3’
poly(A) tails. (2) The hairpin structure that likely forms around the miRNA
sequence of the pri-miRNA acts as a signal for digestion by a double-stranded
(ds) ribonuclease (Drosha) to produce the precursor miRNA (Pre-miRNA). (3)
Exportin-5 mediates nuclear export of pre-miRNAs. (4) A cytoplasmic dsRNA
nuclease (Dicer) cleaves the pre-miRNA leaving 1–4 nt 3' overhangs. The
single-stranded mature miRNA associates with a complex that is similar, if not
identical, to the RNA Induced Silencing Complex (RISC). (5) The miRNA/RISC
complex represses protein translation by binding to sequences in the 3'
untranslated region of specific mRNAs.
• Antisense RNA may be introduced into a cell to
inhibit translation of a complementary mRNA by
base pairing to it and physically obstructing the
translation machinery. This effect is therefore
stoichiometric.
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Ribozyme
• A ribozyme (ribonucleic acid enzyme) is an RNA
molecule that is capable of performing specific
biochemical reactions, similar to the action of
protein enzymes.
• The 1981 discovery of ribozymes demonstrated
that RNA can be both genetic material (like DNA)
and a biological catalyst (like protein enzymes),
and contributed to the RNA world hypothesis,
which suggests that RNA may have been
important in the evolution of prebiotic selfreplicating systems.
The chicken-egg debate: RNA
world （RNA世界假说）
• The RNA world hypothesis proposes that selfreplicating ribonucleic acid (RNA) molecules
were precursors to current life, which is based
on deoxyribonucleic acid (DNA), RNA and
proteins.
• RNA stores genetic information like DNA, and
catalyzes chemical reactions like an enzyme
protein. It may, therefore, have played a major
step in the evolution of cellular life.
DNA（脱氧核糖核酸）
• Deoxyribonucleic acid (DNA) is a molecule that
encodes the genetic instructions used in the
development and functioning of all known living
organisms and many viruses.
• Along with RNA and proteins, DNA is one of the
three major macromolecules essential for all
known forms of life.
• The structure of the DNA double helix（DNA双
螺旋结构）
• Plasmid DNA, chromosome DNA, cDNA, gene
(ORF) structure, DNA methylation, chromosome
structure
DNA Structure
• Base pairing
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Double helix
DNA双螺旋结构模型的建立
• The DNA double helix is
stabilized primarily by two forces:
hydrogen bonds between
nucleotides and base-stacking
interactions among aromatic
nucleobases.
• The double-helix model of DNA
structure was first published in
the journal 《Nature》 by James
D. Watson and Francis Crick in
1953
Chromosome （染色体）
• A chromosome is a single
piece of coiled DNA
containing many genes,
regulatory elements and
other nucleotide sequences.
• Also contain DNA-bound
proteins, which serve to
package the DNA and
control its functions.
诺贝尔医学与生理学奖
1962年
Plasmid（质粒） DNA
• A plasmid is a small DNA molecule that is physically
separate from, and can replicate independently of,
chromosomal DNA within a cell.
• Most commonly found as small circular, double-stranded
DNA molecules in bacteria, plasmids are sometimes
present in archaea and eukaryotic organisms.
• In nature, plasmids carry genes that may benefit survival
of the organism (e.g. antibiotic resistance), and can
frequently be transmitted from one bacterium to another
(even of another species) via horizontal gene transfer.
• Artificial plasmids are widely used as vectors in
molecular cloning, serving to drive the replication of
recombinant DNA sequences within host organisms.
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Plasmid（质粒） DNA
Complementary DNA
•
Complementary DNA (cDNA) is DNA synthesized from a
messenger RNA (mRNA) template in a reaction catalysed by the
enzymes reverse transcriptase and DNA polymerase.
• The major difference between cDNA and its corresponding gene
sequence is that cDNA has no intron sequences, non-coding DNA
sequences punctuated between coding sequences.
Gene（基因）
• A modern working definition of a gene is "a
locatable region of genomic sequence,
corresponding to a unit of inheritance, which is
associated with regulatory regions, transcribed
regions, and or other functional sequence
regions ".
• ORF: Open reading frame(开放阅读框)
• Genetic code(密码子)
DNA codon（密码子）/ Genetic
code（遗传编码）
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Chromosome structure
• Bacterial Chromosome Structure
Prokaryotic cells (bacteria) contain their
chromosome as circular DNA. Usually the
entire genome is a single circle, but often there
are extra circles called plasmids. The DNA is
packaged by DNA-binding proteins.
DNA methylation (甲基化)
Chromosome structure
• Eukaryotic chromosome structure
Eukaryotic cells contain their DNA within the
nuclear membrane. The DNA is wrapped
around the histone core of eight protein subunits,
forming the nucleosome. The nucleosome is
clamped by histone H1. About 200 base pairs
(bp) of DNA coil around one histone.
Gene expression flow
• DNA methylation is a biochemical process involving the
addition of a methyl group to the cytosine or adenine DNA
nucleotides.
• DNA methylation stably alters the expression of genes in cells
as cells divide and differentiate from embryonic stem cells into
specific tissues.
• The resulting change is normally permanent and unidirectional,
preventing one organism from reverting to a stem cell or
converting into another type of tissue.
•Methylation of histone or of DNA usually turns a
gene off.
•Acetylation of histone usually turns a gene on.
•Phosphorylation -- we're not sure what that does.
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Peptides
• Peptides are short chains of amino acid monomers
linked by peptide (amide) bonds, the covalent chemical
bonds formed when the carboxyl group of one amino
acid reacts with the amino group of another. Peptides
are distinguished from proteins on the basis of size, and
as a benchmark can be understood to contain
approximately 50 amino acids or less
Single unit proteins（单链蛋白质 ）
• Contains only one peptide
• Bacterial proteins
• Ribonuclease A
• lysozyme
Multi-unit proteins（寡聚蛋白质）
Protein complexes 蛋白复合体
• Contains 2 or >2 peptides （subunits）
• Contains 2 or >2 proteins
• Eukaryotic proteins
• Linked by non-covalent protein–protein
interactions
• These complexes are a cornerstone of many (if
not most) biological processes and together they
form various types of molecular machinery that
perform a vast array of biological functions.
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Central dogma of molecular biology
(中心法则)
Genetic information flow
• The central dogma of molecular biology is an
explanation of the flow of genetic information within a
biological system.
• It was first stated by Francis Crick in 1958: “The central
dogma of molecular biology deals with the detailed
residue-by-residue transfer of sequential information. It
states that such information cannot be transferred from
protein to either protein or nucleic acid”.
• Marshall Nirenberg said, "DNA makes RNA makes
protein.“
The exceptions (deviations) of central
dogma landed two Nobel prizes
Summary
• Life molecule: DNA, RNA, Protein
DNA
RNA
???
Protein
???
David Baltimore in 1975 for his discovery of Reverse transcriptase (RT)
Stanley Benjamin Prusiner in 1997 for his discovery of prion.
• RNA: mRNA, rRNA, tRNA, tmRNA, microRNA,
antisense RNA, Ribozyme
• DNA: structure, plasmid DNA, chromosome, cDNA, gene
(ORF) structure, DNA methylation, chromosome
structure
• Peptides, single unit proteins, multi-unit proteins, protein
complexes
• Central dogma of molecular biology
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Questions
1. Why RNA is the most likely original molecule
of life?
The mission of scientist
Uncover the law and truth of mother nature
Persist (truth often lies in the hands of minority)
2. Why cells do not use RNA alone as basic life
molecules despite that RNA can both store
genetic information and catalyze biochemical
reactions?
Challenge authority (Respect law of nature more than respect
any person
Comprehensive (no rush to conclusion, self-correct)
3. What is the core definition of central dogma
and how it has been challenged and
supplemented?
A quiz for fun
1. Which month has 28 days?
2. What can’t you ever grab with your right hand?
3. How many eggs can you eat with an empty stomach?
4. Can you imagine something that might travel faster than light?
Curiosity and unlimited imagination
Suggested reading: “The structure of Scientific Revolutions by
Thomas S. Kuhn
Next…
• DNA manipulation: DNA Isolation, gel
electrophoresis, Restriction enzymes
(scissors), ligases, polymerases,
polynucleotide kinases, TDT, DNA
topoisomerases, vectors, amplification,
Southern blot, primer extension, RFLP,
PFGE, Multi-locus sequencing, Whole
genome sequencing, comparative
genomics
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