Dogmas

Francis Crick developed the model of protein synthesis which he called the central dogma (1958) which states that DNA makes RNA makes protein. The dogma emphasises the unidirectional pathway from DNA (the archives of genetic material) by transcription converted to mRNA and then converted into specific amino acid sequences of proteins by translation.

Another step can be added: Amino acid sequences determine protein structure. Most proteins adopt specific 3D conformations dictated by their amino acid sequences alone. Protein structure determines protein function.

This one-way flow requires Darwinian natural selection at the protein level to be a mechanism of evolution – as opposed to direct selection of DNA sequence changes. This is achieved through mutation which generates variation (which changes individual DNA sequences) but does not move a population to a better-adopted state.

The ribosome makes possible the connection between heritable genetic information (as a nucleic acid) and the agents of biochemical activity (proteins). Selection acts as the functions produced by the proteins, and RNAs encoded in the genome and on the regulatory mechanisms.

Some genetic change is non-selective: neutral evolution or genetic drift. Drift is especially important in small populations. The result of both selection and drift are inherited alternations in genomes – including both changes in sequence and changes in allele frequencies. The changes change the nature and expression patterns of the proteins and RNAs in individuals of a population.

What are Proteins ?

Proteins are biological macromolecules that provide 3D structures shaped for many different individual functions. These functions include:

  • Structural Proteins: These proteins include keratins (found in hair and in the skin), the cytoskeleton and coats of viruses.
  • Enzymes: These proteins catalyse the reactions of the metabolism and the replication and transcription of DNA.
  • Antibodies: Antibodies are proteins that recognise and repel invading pathogens and inactive toxins ;
  • Regulatory Proteins: These control the transcription of genes ;
  • Sensors: Sensors detect and implement signals generated within our body and those from the environment we live in;
  • Transporters and pumps : Control the traffic into and out of cells and organelles;
  • Transducers : These are motor proteins that convert chemical to mechanical energy (e.g. for muscle contraction, kinesins and dyneins of intracellular transport, ATP synthases.

A Kinesin in action

 

Proteins: Structure and Function

 

Proteins create the structures for the wide-range of functions by varying the common underlying chemical scheme. They are linear polymers (a macromolecule composed of many repeated sub-remits) that have the same polypeptide backbone. Along the backbone is a variable sequence of side-chains that distinguishes the different proteins. The side-chain at any position is one-of-twenty canonical chemicals which make possible a common synthetic mechanism: ribosomes assemble proteins under the direction of messenger RNA (mRNA) sequences.

The three-dimensional structures of proteins are inherent in their amino acid sequences : natural proteins fold spontaneously to from individual ‘native’ structures.

The polypeptide chain is flexible, and can assume many different spatial conformations which bring into proximity different constellations of sidechains. These constellations interact with one another and with solvent (a substance that dissolves a solute). One of these conformations creates a set of stable interaction which leads to the protein’s native state at equilibrium.

The range of protein structures and functions depends on the variety in the properties of the sidechains. The 20 natural sidechains vary in size and other physiochemical properties.

  • some are polar or charged
    • they can participate in hydrogen bonding or electrostatic interactions with other residues or solvent;
  • charged atoms occur at or near ends of (relatively) long and flexible sidechains;
  • atoms close to backbone are non-polar;
  • two sidechains with positive and negative charge can form a soft bridge;
  • sidechains can be non-polar :
    • Large aliphotic sidechains are hydrophobic (do not like water);
    • The clustering of hydrophobic sidechains on the inside of proteins provides the thermodynamic force for protein-folding.

Source: Introduction to Protein Science – Arther M Lesk

Quickly convert gzip to bzip2

Ever wanted to convert from one compression scheme to another? The long way to do it is to uncompress the original file and delete it, compress the files to the second compression scheme and then delete the intermediate files. This is very time and space inefficient.

The solution

To quickly convert a gzip file to bzip2, use the following command:

You can also use this solution for other types of compression, such as zip. Hope you find this trick useful!

Gmail filter with multiple addresses

Recently I needed to update a Gmail filter for a contact with multiple addresses. To meet this requirement, I added the email addresses to the filter in the following format:

The key is using {} instead of the normal parenthesis, (). So instead of creating multiple filters for the contact, you can simply update the filter to include all the email addresses.

Hope this is a useful tip!

Solving the Even Fibonacci Challenge

The Even Fibonacci Challenge, Problem 2 in the Project Euler Challenge. The modified problem requires adding the even-valued terms in the series which do not exceed a given integer N.

My solution is as follows:

The nature of genetic code

Three bases constitute a codon, that stand for one amino acid. Out of the 64 possible 3-base codons, 61 specify amino acids while the other 3 are stop signals. The ribosomes scan a messenger RNA 3-bases at a time and bring in the corresponding amino acids to link to the growing protein chain. When they reach a stop signal, they release the completed protein.

Genetic Code

Genetic Code

 

How genes direct the production of polypeptides

Gene expression is the process by which a gene product (RNA or polypeptide) is made. Two steps (transcription and translation) are required to make a polypeptide from the instructions in a DNA gene.

 

In transcription, an enzyme called RNA polymerase makes a copy of one of the DNA strands (an RNA copy).

 

In translation, this RNA (messenger RNA or mRNA) carries the genetic instructions to the cell’s protein factories called ribosomes. The ribosomes “read” the genetic code in the mRNA and put together a protein according to its instructions.

 

Ribosomes already contain molecules of RNA (ribosomal RNA or rRNA). Experience shows that ribosomes are non-specific translation machines that can make an unlimited number of different proteins, according to the instructions in the mRNAs that visit the ribosomes.

 

The process of translation

The process of translation

One gene, one polypeptide rule

Transcription and Translation

Gene Replication

DNA is a double helix – two DNA strands wound around each other. The bases of each strand are on the inside of the helix, and a base on one strand pairs with one on the other in a very specific way. DNA has only four different bases:

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Wherever we find an A in one strand, we always find a T in the other; wherever we find a G in one strand, we always find a C in the other. The strands are complementary. If we know the base sequence of one, we automatically know the sequence of the other.

The process of replication takes one strand (after they come apart) and enzymes build new partners for them using the old strands as templates following the Watson-Crick base-pairing rules. This process is called semi-conservative replication since one strand of the parental double helix is conserved in each of the daughter double helices.

A Schematic Diagram of DNA Replication

A Schematic Diagram of DNA Replication

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