Genomic- Week 1 Lecture 2

Genome

• The entire set of DNA of an organism

• Includes:

  • Eukaryotic cell

  • chloroplast DNA

  • mitochondrial DNA

  • nuclear DNA

Fundamentals for Structural Genomics

DNA

• DNA (deoxyribonucleic acid) is a molecule

  • double stranded

  • twists like a spiral staircase

  • backbone: deoxyribose sugars & phosphates

  • inside: nucleotides / nitrogenous bases

• Alphabet of 4 letters: A T C G

• Sequence gives the meaning

• Reverse complement – If you know one strand, you know the other

• DNA carries genetic information

Genome Size

• Measured in number of base pairs (bp)

• Nitrogenous bases:

  • Guanine (G) pairs with Cytosine (C)

  • Adenine (A) pairs with Thymine (T)

  • Hydrogen bond between two complementary nitrogenous bases

  • Sugar-phosphate backbone

• Human genome has ~3 billion bp – 3 Gb (gigabases)

• Distributed in chromosomes (not continuous) = 15 Kb

• Conversions:

  • 1 bp

  • 1,000 bp = 1 Kb

  • 1,000,000 bp = 1 Mb

  • 1,000,000,000 bp = 1Gb

• Genome size varies across species

  • Number of chromosomes and genes also varies, in different ways

  • Challenge with non-model species – Unknown genome size

  • Often due to variation in amount of non-coding DNA

    • Although some part might also be number of genes

DNA Inheritance

• DNA is inherited from parents

• How are the 3 Gb distributed?

  • Complete set of genetic information

  • Autosomes: 1-22

  • Sex chromosomes: X, Y

  • For each chromosome pair, one comes from each parent.

    • Both have the same genes arranged in the same order, but with slight variations in their DNA sequences.

• Genome size refers to the haploid version

  • Human genome:

    • Haploid size = 3 Gb (Egg / Sperm (n))

    • Diploid genome = 6 Gb (All other cells (2n))

DNA Packing

• DNA is tightly packed

  • Stretched human genome = 6 ft in length

  • Chromatin – condensed complex of DNA and proteins

• To be copied or read, condensed structure has to be undone

• Alternative strategies of sequencing allow to save information on conformation

Fundamentals for Functional Genomics

Genes

• Genomes contain protein-coding genes (among other things)

  • Segment of DNA with instructions for making a specific protein or set of proteins

• Genes code for proteins (coding regions)

• Non-coding regions:

  • regulatory sequences

  • unknown functions

  • repetitive sequences

  • some transcribed but not translated

• Molecules made of amino acids – Do everything in our body

  • Amino acid sequence defines the structure

  • Structure/shape determines function

• Genes are transcribed into mRNA, which are translated to proteins

• Central dogma of molecular biology: How genetic information flows from DNA to RNA to proteins

Transcription

• Genes are transcribed into mRNA

• RNA polymerase (an enzyme/protein) converts DNA into RNA transcripts

• RNA is a molecule (ribonucleic acid)

  • single stranded

  • backbone: ribose sugars & phosphates

  • inside: nucleotides – Uracil (U) instead of Thymine (T)

  • less stable than DNA

Translation

• mRNA is translated to protein

• Ribosome (complex of proteins and rRNA) converts mRNA into chain of amino acids

• mRNA: messenger from DNA to protein

• tRNA: transfers amino acids to the translation process

• rRNA: part of the ribosome (along with proteins) for building protein

• Multiple types of RNA participate in gene expression

Genetic Code

• The genetic code gives the rules of translation

• Each codon (sequence of 3 nucleotides) is converted to one amino acid, or signals the end of protein synthesis

• The genetic code is redundant

  • Multiple codons code for the same amino acid

Mutations

• Mutations in coding DNA do not necessarily change protein function

• Point mutation: substitution of a single base

  • Silent: has no effect on the protein sequence (Synonymous mutations)

• Non-synonymous mutations can lead to abnormal proteins, loss of function, disease

  • Missense: results in an amino acid substitution

Genetic Variation

• There is genetic variation within populations

  • Mutations are major source

  • Natural differences in DNA sequences between individuals

  • Range of traits & potential for adaptation to changing environments

    • Raw material for evolution through natural selection

• Genetic variation of a gene is represented by different alleles

  • Locus: physical location of a gene on a chromosome

  • Alleles: genetic variations of a gene

  • Genotype determines phenotype

• Populations can have multiple variants/alleles of same gene

• Diploid individuals can have two

  • Homozygous = two identical alleles

  • Heterozygous = two different alleles

• There is genetic variation within one individual

Comparative Genomics

• Conserved x Variable regions

  • Conserved: have not changed much over time

    • Likely because of important function across species

  • What allows us to investigate how organisms are evolving (= genetically changing over time)