From Bi 150 Lecture 0 October 4, 2012 An introduction to molecular biology . . .

but you will learn the cell biology in this course

3 x 109 base pairs

Lander et al

Humans have 22 pairs of chromosomes, plus the X and Y. Males are XY; females are XX.

A. Each chromosome is painted with a unique combination of fluorescent dyes

B. We have arranged the chromosomes to form pairs.

Garland; Little Alberts Fig 5-12

Genes can be localized crudely by hybridizing a fluorescent nucleotide probe to chromosomes

2 m 6 distinct genes are probed b di in this hi i image

Little Alberts Fig 10-16 Seuss 1959

Complete DNA sequence as scripture (surf NCBI)

single-nucleotide g polymorphisms (SNPs)

orthologs in other species mutations that cause disease basic sequence proteins that bind to the sequence and regulate expression

chromosomal location RNA splicing

RNA sequence RNA abundance protein sequence

protein function protein structure

How much coding sequence is in the genome?

22,000 genes x 400 codons/protein x 3 bases/codon = 26.4 million base pairs, or < 1% of the genome! g

The remainder . . . 1. Repetitive elements (junk? selfish DNA?)

2.

Regulatory regions

3.

Introns

Gene activation involves regulatory regions

Little Alberts Fig. 8-15 Garland publishing

Components of Expression Gene (DNA) coding sequences noncoding g sequences q

exon

intron transcription (mRNA synthesis) splicing (introns removed)

messenger RNA (mRNA)

translated sequences translation

untranslated sequences

protein

Protein synthesis and degradation

A. synthesis

B. degradation proteolysis proteolysis protein + Greek, breakdown

Modified from Little Alberts Panel 2-5

the tRNA synthetase translates the genetic code, because it contacts (a) the amino acid

(c) in some cases, other parts of the tRNA

(b) the anticodon loop

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receptor
a molecule on the cell surface or in the cell interior that has an affinity for a specific molecule (the ligand).
Latin, to tie

Most drug receptors are proteins.

Greek, first

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Protein Folding vs. Inverse Folding = Computational Protein Design

Protein Folding (no degeneracy)

Set of All Structures

Inverse Folding (large degeneracy)

Set of All Sequences Several ways y to make an arch

Individual amino acids

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Protein degradation is accomplished primarily by proteolytic enzymes

The genome encodes hundreds of proteolytic enzymes. They vary in -- sequence specificity for the cut cut -- cellular expression -- organelle of expression

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Cells often mark proteins for proteolysis by attaching strings of the protein, ubiquitin.

strings of ubiquitin to be proteolyzed

other protein

modified from Little Alberts Fig 18-7

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Controlled proteolysis takes place in the proteasome

shorter

modified from Little Alberts 1st edition Fig 7-32

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