Nucleic Acids Where are they found in nature and What do they look like

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Nucleic AcidsWhere are they found in
nature?andWhat do they look like?
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Genomes
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DNA molecules are packaged in the cell as
structures called chromosomes. Bacteria have a
single chromosome. Eukaryotes have multiple
chromosomes. A single chromosome contains
thousands of genes, each encoding a protein. All
of an organisms chromosomes make up the
genome. Humans have 46 chromosomes. The human
genome has about 3 billion nucleotide base pairs.
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The Human Genome
http//www.ncbi.nlm.nih.gov/genome/guide/human/
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How is DNA packaged into a cell?
E. coli has a single double-strandedDNA molecule
as its genome. There are 4,639,221 base pairs in
the E. coli genome. The DNA is 1.7 mM long, 850
times the length of an E. coli cell.
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plasmid
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Large DNA moleculesare compacted in a cellby
supercoiling.
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Relaxed and supercoiled plasmid DNA
supercoiled
relaxed
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DNA in eukaryotic cells is packaged into
nucleosomes,which contain proteins called
histones.
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Electron micrograph of nucleosomes
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DNA wrapped around a histone core (side view)
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Nucleosomes are packaged to form 30 nm fibers
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Compaction of 30 nm fibers uses nuclear scaffolds
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The nucleus of a mammalian cell contains the DNA
(genome)
Nucleus
Cytoplasm
Lipid bilayer
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Pathways of information flow
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Proteins are synthesized in the cytoplasmRNA
carries the genetic information to the cytoplasm
Nucleus
Cytoplasm
Lipid bilayer
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In eukaryotes, genes contain exons (coding
regions)and introns (non-coding
regions). Prokaryotic genes do notcontain
introns.
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Exons and Introns
ATGGACTCAC CACAAGAAGA AGATGTGGAG GTGAAGAAGA
AGGCGACGGA 50 AGTGGAGTAC GTTGTCAGGT CGTTGGCATC
AGATGAGCCA GCTCCATTTT 100 CCGACGAGGC GTTGGCGATT
ACGACAAGAG AAGCGGTGGA TTATTCAAAG 150 AAAATAACTT
TGGCAATGGC AGAAGCTAAT GAGGgtgaga
atttttaatt 200 tgaaaatatt atattggaat atacttgaaa
tttctaatag taaaaaggaa 250 aattagccat ttgcgaaaat
ttgcgagtta taactagaaa ataccgtcta 300 cgttctcgaa
acatttgaat attagaaaaa aaagagtgtg
tgcacttaaa 350 gagtacagaa gttgccacga ctctctatta
ctcagttttt cttcgttttt 400 tctctttatt tgcttcaaaa
atatctgtag ctttctgtaa cttacagCTG 450 GCCGACCTGT
GCGAATTTAT GCTGATGGAA TTTATGATCT
GTTCCATCAT 500 GGGCATGCGA ATCAACTTCG CCAAGTGAAG
AAAATGTTCC CAAATGTCTA 550 CCTTATTGTT GGAGgtttga
ttttttaatc tttttcaatt atgattttca 600 tttcaaattt
cagTTTGTGG TGATCGCGAC ACTCACAAGT
ACAAAGGAAG 650 AACAGTCACT TCAGAAGAAG AACGTTACGA
TGGTGTTCGG CACTGTCGGT 700 ACGTTGATGA AGTCTACAGA
GAGGCTCCAT GGTTTTGTAC TGTCGAGTTT 750 TTGAAAAACC
TTAAAGTTGA TTTCATTGCT CATGACGCTA
TTCCATATGT 800 TGCACCAGGA GAGGAGGACT TGTATGAGAA
GTTTCGTAGA GAAGGAATGT 850 TCTTGGAAAC GGAACGAACT
GAAGGTGTCT CTACAAGTGA CGTCGTCTGC 900 AGAATCATCC
GTGATTACGA TAAGTACGTG CGTCGTAATT
TGCAAAGAGG 950 ATATTCACCG AAAGAGCTCA ACGTCGGATT
TTTGGCGgta aaagttgaga 1000 atttcgaaat aataaaaaaa
ttttatgttt tagGCAAGTA AGTATCAAAT 1050 TCAAAACAAA
GTCGACTCGT TGAAAAGCAA GGGAATCGAG CTTCTGTCCA 1100
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DNA 5 ATGTTGCCTAAGACCTCGGGGACGCGGGCCACTTCGCTGGG
GAGGCCGGAGGAGGAGGAG 1 -------------------
----------------------------------- 60 DNA
3 TACAACGGATTCTGGAGCCCCTGCGCCCGGTGAAGCGACCCCTCCGG
CCTCCTCCTCCTC   RNA 5 AUGUUGCCUAAGACCUCGGGGACGC
GGGCCACUUCGCUGGGGAGGCCGGAGGAGGAGGAG   protein M
L P K T S G T R A T S L G R P E E
E E -   GATGAGCTGGCCCACCGCTGCAGCAGCTT
CATGGCCCCGCCTGTGACCGACCTGGGCGAG 61
---------------------------------------------
--------- 120 CTACTCGACCGGGTGGCGACGTCGTC
GAAGTACCGGGGCGGACACTGGCTGGACCCGCTC  
GAUGAGCUGGCCCACCGCUGCAGCAGCUUCAUGGCCCCGCCUGUGACCGA
CCUGGGCGAG   D E L A H R C S S
F M A P P V T D L G E -  
CTGCGAAGGAGGCCGGGCGACATGAAGACCAAGATGGAGCTGCTGATTCT
GGAGACCCAG 121 ---------------------------
--------------------------- 180
GACGCTTCCTCCGGCCCGCTGTACTTCTGGTTCTACCTCGACGACTAAGA
CCTCTGGGTC   CUGCGAAGGAGGCCGGGCGACAUGAAGA
CCAAGAUGGAGCUGCUGAUUCUGGAGACCCAG   L R
R R P G D M K T K M E L L I L E T
Q -
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Telomeres
Telomeres are sequences at the end of
eukaryoticchromosomes that help stabilize the
chromosome. Telomeres are repeats of the
following sequence 5-(TxGy)n x and y 1 to
4 3-(AxCy)n The TG strand is
longer 5-TTTGGTTTGGTTTGGTTTGGTTTGGTTTGG 3-AAAC
CAAACCAAACC Can be gt10,000 nucleotides in
mammals. The ends of the chromosome are
replicated by the enzyme telomerase.
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Telomerase
Telomerase is a protein that contains a 150
nucleotide RNA. The RNA contains multiple
3-(AxCy)n repeat sequences. Telomerase is a
reverse transcriptase that uses the RNA as a
template for synthesis of the 5-(TxGy)n strand
of DNA. Cellular polymerases are thought to
synthesize the corresponding complementary
(AxCy)n sequences. The remaining single stranded
(TxGy)n sequence is folded back in a T loop
structure, protecting it from degradation.
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Polymerization bytelomerase
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Proteins called TRF1 and TRF2 bind the looped DNA
at the end of the telomere, protecting the DNA
from nucleases andDNA repair machinery.
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T-loop at the end of a telomere Fig 26-37
Line 5,000 nucleotides
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Telomeres and aging
There appears to be a relationship between the
length of telomeres at the end of chromosomes
and the age of an individual. The older you
are, the shorter your telomeres are. Germ-line
cells (reproductive cells) contain telomerase
activity. Non-germ-line cells (somatic cells) do
not contain telomerase activity. We have a
certain length of telomeres that we are born
with. As we age, the telomeres get shorter. Is
our life-span pre-determined by the length of our
telomeres?
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Internet Resources

• Nucleic Acids
• National Center for Biotechnology Information
  (NCBI)
• National Library of Medicine (NLM)
• National Institutes of Health (NIH)

http//www.ncbi.nlm.nih.gov/
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http//www.ncbi.nlm.nih.gov/
http//www.ncbi.nlm.nih.gov/Database/index.html
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GenBank
GenBank is the NIH genetic sequence database, an
annotated collection of all publicly available
DNA sequences. GenBank (at NCBI), together with
the DNA DataBank of Japan (DDBJ) and the European
Molecular Biology Laboratory (EMBL) comprise the
International Nucleotide Sequence Database
Collaboration. These three organizations exchange
data on a daily basis. GenBank grows at an
exponential rate, with the number of nucleotide
bases doubling approximately every 14 months.
Currently, GenBank contains more than 13 billion
bases from over 100,000 species.
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The Databases
Nucleotide Database The Nucleotide database
contains sequence data from GenBank, EMBL, and
DDBJ, the members of the tripartite,
international collaboration of sequence
databases. EMBL is the European Molecular Biology
Laboratory (EMBL) at Hinxton Hall, UK, DDBJ is
the DNA Database of Japan (DDBJ) in Mishima,
Japan. Sequence data is also incorporated from
the Genome Sequence Data Base (GSDB), Santa Fe,
NM. Patent sequences are incorporated through
arrangements with the U.S. Patent and Trademark
Office (USPTO), and via the collaborating
international databases from other international
patent offices. Genome Database The Genome
database provides views for a variety of genomes,
complete chromosomes, contiged sequence maps, and
integrated genetic and physical maps.
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The Databases
Protein Database The Protein database contains
sequence data from the translated coding regions
from DNA sequences in GenBank, EMBL and DDBJ as
well as protein sequences submitted to Protein
Information Resource (PIR), SWISSPROT, Protein
Research Foundation (PRF), and Protein Data Bank
(PDB) (sequences from solved structures). Structu
re Database The Structure database or Molecular
Modeling DataBase (MMDB) contains experimental
data from crystallographic and NMR structure
determinations. The data for MMDB are obtained
from the Protein Data Bank (PDB). The NCBI has
cross-linked structural data to bibliographic
information, to the sequence databases, and to
the NCBI taxonomy.
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The Databases
OMIM Database The OMIM (Online Mendelian
Inheritance in Man) database is a catalog of
human genes and genetic disorders. OMIM and its
Help document OMIM Help. Taxonomy Database The
Taxonomy database contains the names of all
organisms that are represented in the NCBI
genetic database by at least one nucleotide or
protein sequence. For the context of the Taxonomy
database see Taxonomy and Taxonomy
FAQs. Bookshelf The Bookshelf has a collection of
Biomedical books that are linked in Entrez and
can also be separately searched at Bookshelf.
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http//www.ncbi.nlm.nih.gov/
http//www.ncbi.nlm.nih.gov/Database/index.html
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BLAST SEARCH
What is BLAST? BLAST (Basic Local Alignment
Search Tool) is a set of similarity search
programs designed to explore all of the available
sequence databases regardless of whether the
query is protein or DNA. The scores assigned in a
BLAST search have a well-defined statistical
interpretation, making real matches easier to
distinguish from random background hits. BLAST
uses an algorithm which seeks local as opposed to
global alignments and is therefore able to detect
relationships among sequences which share only
isolated regions of similarity.
The core of NCBI 's BLAST services is BLAST 2.0
otherwise known as "Gapped BLAST". This service
is designed to take protein and nucleic acid
sequences and compare them against a selection of
NCBI databases. Instead of relying on global
alignments (commonly seen in multiple sequence
alignment programs) BLAST emphasizes regions of
local alignment to detect relationships among
sequences which share only isolated regions of
similarity. Therefore, BLAST is more than a tool
to view sequences aligned with each other or to
calculate percent homology, but a program to
locate regions of sequence similarity with a view
to comparing structure and function.
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The BLAST search pages allow you to select from
several different programs
Below is a table of these programs.

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Nucleotide Databases

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Nucleic Acid SequenceWhat does it encode?
CGTGATGAACGGCTTCGAGCGATACGAGGGAGTGCGTCACTGCCGCTATG
TGGACGAGTTGCAGATCGTCCAGAATGCGCCATGGACTCTGTCCGATGAA
TTCATCGCCGACAACAAAATCGACTTTGTGGCCCACGACGACATTCCGTA
TGTAACCGATGGCATGGACGACATCTATGCTCCTCTCAAGGCGCGCGGCA
TGTTTGTGGCCACGGAGCGCACTGAGGGTGTGTCCACCTCGGACATCGTA
GCCCGGATCGTCAAGGATTACGATCTGTATGTGCGTCGTAATCTGGCCAG
AGGCTATTCGGCCAAGGAACTCAATGTGTCGTTCCTGTCCGAGAAGAAGT
TCCGGCTGCAGAACAA