Molecular Phylogenetic Analysis

• Phylogenetics - is the science of estimating and

  analyzing evolutionary relationships.
• Molecular biology often helps in determining genetic relationships between different organisms.
• Nucleic acids (DNA and RNA) and proteins are 'information

  molecules - retain a record of an organism's evolutionary history.
• Approach - compare nucleic acid or protein sequences from

  different organisms using computer programs and estimate the evolutionary relationships based on the degree of homology between the sequences.
• The nucleotide or amino acid differences within a gene

  reflect the evolutionary distance between two organisms.
• the sequence of the small-subunit ribosomal

  RNA (rRNA) is widely used in molecular phylogeny.
• Molecular Phylogeny - A set of techniques that enable the

  evolutionary relationships between

  DNA sequences to be inferred by

  making comparisons between those

  sequences.
• Molecular phylogenetics predates DNA sequencing by several decades. It is derived from the traditional method for classifying organisms according to their similarities and differences.
• Linnaeus (18th century) - objective was to place all

  known organisms into a logical classification which he

  believed would reveal the great plan used by the

  Creator - the Systema Naturae.
• Linnaeus unknowingly laid the framework for later

  evolutionary schemes by dividing organisms into a

  hierarchic series of taxonomic categories, starting

  with kingdom and progressing down through phylum,

  class, order, family and genus to species.
• The naturalists of the 18th and early 19th centuries

  likened this hierarchy to a ‘tree of life’ an analogy that

  was adopted by Darwin (1859) in The Origin of

  Species.
• Carl Linnaeus - Swedish biologist and physician who

  formalised binomial nomenclature, the modern

  system of naming organisms. He is known as the

  "father of modern taxonomy". Many of his

  writings were in Latin; his name is rendered in

  Latin as Carolus Linnæus and, after his

  1761 ennoblement, as Carolus a Linné.
• Phylogeny - classification scheme that indicates the evolutionary relationships between organisms.
• Homolog - A gene similar in structure and evolutionary origin to a gene in another species.
• Orthologs - genes in different species that evolved from a common ancestral gene by speciation, and, in general, orthologs retain the same function during the course of evolution.
• Xenolog - A type of ortholog where the homologous sequences are found in different species because of horizontal gene transfer.
• Xenolog - A type of ortholog where the homologous sequences are found in different species because of horizontal gene transfer.
• Paralog - One of a set of homologous genes that have diverged from each other as a consequence of genetic duplication.
• Analog - in a separate species, an unrelated gene has a similar function (Gene C) but has a separate evolutionary origin
• Phylogenetic Tree - is a diagram that depicts the lines of

  evolutionary descent of different species,

  organisms, or genes from a common ancestor.
• Topology – pattern of a phylogenetic trees
• External Node - The end of a branch in a phylogenetic tree, representing one of the organisms or DNA sequences being studied.
• Internal Node - A branch point within a phylogenetic tree, representing an organism or DNA sequence that is ancestral to those being studied.
• Branches - indicate the degree of difference between the genes represented by the nodes
• COMT gene (Catechol-O-Methyltransferase) - involved in the inactivation of catecholamines such as dopamine, norepinephrine and catecholestrogens, helps the body get rid of excess Dopamine, Epinephrine, Norepinephrine and Estrogens.
• Steps in Phylogenetic Tree Construction/Reconstruction using DNA sequences

  1. Aligning the DNA sequences and obtaining the comparative data that will be used to reconstruct the tree;
  2. Converting the comparative data into a reconstructed tree;
  3. Assessing the accuracy of the reconstructed tree;
  4. Using a molecular clock to assign dates to branch points within the tree.
• Distance-based methods

  • Neighbor-Joining – (NJ)
  • Unweighted Pair Group Method with Arithmetic mean - (UPGMA)
  • Minimum evolution method
  • Fitch-Margoliash method
• Character-based methods

  • Maximum-Likelihood
  • Maximum Parsimony (MP)
• Maximum- Likelihood - Find the model which has the highest probability of producing the observed data

  • Oldest estimation method

  • Not useful for complex estimation
• Neighbor- Joining - Based on the Minimum Evolution method

  • Joins each step, the closest subtrees that are not

  already joined

  • Two taxa that are connected by a single node in

  unrooted tree
• UPGMA - Simplest method/algotrithm which result to rooted trees

  • Developed by Sokal and Michener (1958)

  • Starts with a matrix of pairwise distances
• Maximum Parsimony - Explain the observed sequences with a minimum number of

  substitutions

  • Best for small sets of sequences with high similarity
• BIOINFORMATICS WEBSITES/ TOOLS

  • NCBI Blast
  • MEGA X
• MEGA X - Molecular Evolutionary Genetics Analysis
• MEGA X Applications

  • Clarified evolutionary relationships ofhumans and other primates
  • Origin of viral diseases in humans
  • Tool in the study of human prehistory
  • Plant breeding
  • Animal breeding