Bioinformatics Lecture 2: molecular biology. Essential concepts of evolution – The Basic Tenets of evolution: Adaptability and stability in an environment.

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)