Bioinformatics Lecture 2: molecular biology

Essential concepts of evolution – The Basic Tenets of evolution: Adaptability and stability in an environment mutations/ survival of fittest – Basic Tenets of inheritance: How physical traits (phenotype) are transmitted at the genetic level (genotype) Different variants of the same gene (alleles) Relationship between alleles: dominant /recessive Two forms of inheritance,autosomal / x-linked, that are associated with the type of chromosome: non sex linked/sex linked (gender determination ) chromosomes

Stability and Adaptability Stability: cell/tissue remains in an unchanged state. Cell structure protects it from the external environment; nuclear membrane protects the DNA…. Adaptability: is essential to survival and creating the diversity of life that exists occur via mutations: A mutation is a change, mostly permanent, to the DNA and can be generalised into 2 forms: – Type: chromosomal “mutations” and point mutations – Cell location of mutation Somatic mutation: Diploid (2n) somatic cells Germ-line mutation: Haploid (n) reproductive cells [gametes] – Chromosome Location ( subset of cell location mutations): Autosomal (number 1 to 22): Huntington’s syndrome X-linked X/Y chromosome: Haemophilia

Chromosome Mutation: non-dysjunction. Non-dysjunction abnormality: – Cross-over is an integral part of meiosis and ensure greater diversity is passed from one generation to the next “parent to child” [refer to lecture 1] and an essential element is: dysjunction – However, non-dysjunction can lead to conditions such as Down’s syndrome; here one of the gamets reproduction cells) has 2 (number 21 chromsomes) due to non-disjunction [see next slide] while the other is normal has 1 (number 21)

Types of meiotic Non-dysjunction Adapted from [1] fig 6.1 p113

Chromosome mutations: deletion Deletion: – A chromosome breaks in one place or more places – The part that “falls off” the chromosome is lost – Most often fatal unless small portion lost (cri- du-chat syndrome: deletion in chromosome 5)

Chromosome Mutations Adapted from ref [1] p. 121

Chromosome mutations: duplication Duplication: – Due to error in cross- over or error in duplication prior to meiosis: – Can lead to “gene redundacy”, some physical “abnormality or even increase genetic variability.

Chromosome mutations: inversion Inversion: – No change to the amount of genetic material – A segment of the chromosome is turned around by 180 degrees – The physical consequences is minimal

Chromosome Mutations: translocation Translocation: Reciprocal and non reciprocal: – The movement of a chromosome segment to another part of the genome (between non-homologous chromosomes). – Genetic information is not lost or gained but only rearranged. – In reciprocal both chromosomes swap sections – In non reciprocal one loses a section and it is added to the other.

Point Mutations A Mutation affects only one DNA molecule – Can, but not always, change the type of amino acid [see later] – Substitution: Two types A /G is called a transition; T/C is called a transversion – Insertion : causes a frameshift to the left – the resulting sentence is non sense – Deletion : causes a frameshift to the right: the resulting sentence is non sense Note In genetics the bases (letter of a DNA molecule) are read in sets of three, where each 3 “can” have different result; just as in this example using 3 letter words).

Mutations: Physical (Phenotypic) effects Mutations “can” alter the current (wild type) protein [Phenotype] by changing the underlying Genotype Physical effects (phenotype) are: – Loss of function [can be fatal]: Null mutation (complete loss of function) Partial: can alter either dominant /recessive alleles ; so e.g. if it effects recessive then only homozygous recessive trait is affected – Gain in function: mostly produces a dominant trait – No affect: neutral mutations. Most mutations occur in non-coding regions and are referred to as

Inheritance If a gene has a two or more variants then these are called alleles; alleles are the result of mutations in gene. The presence of such alleles is the basis of differences between members of a species; Tall/dwarf [in certain plants]. Therefore each trait (phenotype/physical manifestation ) has two alleles associated with it. One on the chromosome from the male and one from the female; or one on each chromosome [in the chromosome pair]

Types of alleles-> Phenotype Dominant/recessive system – the dominant allele is capitalised/ recessive is lower case – In heterozygous only the dominant trait is seen. – In the homozygous it depends it can be either. Homozygous dominant: DD (Tall) Homozygous recessive: dd (dwarf ) Heterozygous: Dd (Tall) Incomplete / semi-dominance (snap dragon) – No allele dominant and mixed phenotype (red and white giving pink) Co-dominant (e.g. blood groups) – The phenotype of both alleles are equally expressed; AB, AA, BB, OO

Classical (autosomal) Mendelian Inheritance Somatic Monohybrid cross Adapted from ref [1] p42

Inheritance: Questions This is a dominant/recessive inheritance system. F1: stands for cross- pollination. What conclusion can you draw from F1 results? F2 is self pollination: How the ratios are obtained. For each example determine: – Which is the dominant/recessive trait. Adapted from ref [1] p. 39

X-linked inheritance Haemophilia: (a classical case is son Alexei of last tzar of Russia who was related to queen Victoria) – X chromosome has the normal/defective gene (H/h) – Y chromosome has no gene (smaller in size) – Defective allele is recessive – Male is XY and Female is XX – Homozygous defective results in the disease This includes a defective allele in males – Homozygous/heterozygous normal results in no physical effects.

Illustration of royal disease

Possible Exam Distinguish how x-linked/autosomatic mutations are transmitted throughout a population; illustrating you answer with suitable examples. Explain how mutations are essential for the adaptive character of living organisms and distinguish between the different types of mutations

Reference Klug et al; Essentials of Genetics 7ed – Chapter 6/ 14 (mutations) and Chapter 3 (inheritance)