Topic 4.1 Chromosomes, Genes, Alleles and Mutations

Gene A heritable factor controlling a specific trait or characteristic A heritable factor controlling a specific trait or characteristic A segment of DNA coding for a polypeptide sequence (or tRNA, rRNA or regulates other genes) A segment of DNA coding for a polypeptide sequence (or tRNA, rRNA or regulates other genes) Gene Trait: petal color Gene: DNA that leads to petal color

Allele A form of a gene A form of a gene Alleles for a gene are found in the same locus (location on the chromosome) Alleles for a gene are found in the same locus (location on the chromosome) They have a similar base sequence (may only be different by one base) They have a similar base sequence (may only be different by one base) Lead to an alternate version of a trait, e.g. blue petals. Lead to an alternate version of a trait, e.g. blue petals. DNA  polypeptide  enzyme  pigment  pink petals GATTCGATCTTA DNA  polypeptide  enzyme  pigment  blue petals GATTCGATTTTA

Eukaryotic chromosomes DNA strings organized by proteins DNA strings organized by proteins Each contains many genes Each contains many genes Part of a chromosome with most of the histones removed

Homologous chromosomes Have the same genes (but may have different alleles) in the same order Have the same genes (but may have different alleles) in the same order Will have the same size, centromere location. Will have the same size, centromere location. Found in pairs (inherited maternally and paternally) Found in pairs (inherited maternally and paternally) From mother From father Locus for petal color gene Blue petal allele Pink petal allele Sister chromatids Chromosome #4

Diploid Haploid Two copies of each chromosome (one from each parent) Two copies of each chromosome (one from each parent) Somatic (body) cells Somatic (body) cells 2n = 46 in humans 2n = 46 in humans One copy of each chromosome One copy of each chromosome Gametes (sperm and egg cells) Gametes (sperm and egg cells) n = 23 in humans n = 23 in humans

Chromosomes in Humans 22 homologous pairs 22 homologous pairs 2 sex chromosomes (usually XX or XY) 2 sex chromosomes (usually XX or XY) A karyotype (organized picture of an organism’s chromosomes) of a human. Could sickle cell anemia be diagnosed using a karyotype? Explain.

Genome: all of the genetic information of an organism + two plasmids A bacterial genomeOne of the smallest of the 24 chromosomes in the human genome (simplified)

Mutations: how alleles are formed Gene mutation: a change in the base sequence in the DNA of a gene Gene mutation: a change in the base sequence in the DNA of a gene Caused by damage to DNA or an error in copying (replication error) Caused by damage to DNA or an error in copying (replication error)

Sickle Cell Anemia A base substitution mutation created the sickle-cell allele. In DNA that codes for part of hemoglobin, just one nitrogen base is changed.

Sickle-cell anemia: details Red blood cells carry oxygen in hemoglobin (made of 2 α and 2 β subunits) Red blood cells carry oxygen in hemoglobin (made of 2 α and 2 β subunits) There are 146 codons in β – hemoglobin, the 6 th is mutated There are 146 codons in β – hemoglobin, the 6 th is mutated The 6 th codon (sense DNA) The 6 th codon (sense DNA) –Normal: GAG → glutamic acid (hydrophilic) –Sickle cell: GTG → valine (hydrophobic) Causes hemoglobin to polymerize, twisting the shape of red blood cells Causes hemoglobin to polymerize, twisting the shape of red blood cells

Two normal alleles: No sickle cell, no protection from malaria Two sickle cell alleles: Sickle cell disease One normal, one sickle cell allele: No sickle cell, protection from malaria

Malaria and sickle cell allele distributions Malaria Why is the sickle cell allele common where malaria is found?

More information about MUTATIONS Base substitution: one nucleotide substituted for another Base substitution: one nucleotide substituted for another TTAGCG → TCAGCG antisense DNAmRNA amino acid Silent: GGA → GGCCCU → CCG pro → pro Missense: TGA → TTAACU → AAU thr → asn Nonsense: ACG → ACTUGC → UGA cys → STOP

Frameshift mutation – adding or removing nucleotides, so the “frame” of the codons changes Frameshift mutation – adding or removing nucleotides, so the “frame” of the codons changes ORIGINAL Antisense DNA TAC GGT CTC ACG TCC ACT mRNA AUG CCA GAG UGC AGG UGA Amino acid sequence: Met (start) – pro – glu – cys – arg - STOP MUTANT Antisense DNA TAC TGG TCT CAC GTC CAC T mRNA AUG ACC AGA GUG CAG GUG A Amino acid sequence: Met (start) – thr – arg – val – gln – val