Friday, April 20, 2007

9 - Inside the Genome

What is the genome ?[1]

Loosely speaking, the genome is a sequence of chemical compounds that lie along the chromosomes in the cell of a living organism.

I have heard of the human genome, are we talking about that.

Yes and more, but first let me clarify that there is nothing called the human genome. Every individual living organism has its own specific sequence of these chemical compounds so there are as many genomes in existence at any point of time as there are living organisms.

So what is that was recently discovered as the human genome.

In every species of living organisms, the genome corresponding to each individual is by-and-large similar and because they are similar they are said to belong to the same species.

That means that your genome and my genome is similar ? To what extent ?

To the extent of nearly 99.99% perhaps one in every 10000 element is different and that is why you are what you are – the skeptic – and I am what I am, the seeker !!

So what is the human genome ?

As I said, the 99.99% of the sequence that is common to all individual members of the species is often referred to as the genome of the species.

So there is a genome for human and there is a genome for chimpanzees ?

If you understand the genome of the species in the way that I have just defined, then yes, there is a genome for human being and there is a genome for chimpanzees and from what I know, they are 97% similar.

Fine, now that I am clear on the definition of the genome, can you please explain what these sequences are all about.

A sequence or pattern – and remember how we stressed on the importance of patterns earlier – is of immense significance in living organisms but before I begin let me state that we will be discussing two kinds of sequences.

What are they ?

The sequence of bases that exists in the chromosomes, also called the genotype, and the sequence of amino acids that exist in a protein, also called the phenotype.

A bit confusing.

Don’t panic, just remember the two words genotype and phenotype .. but first let us begin with the genotype.

What is that ?

Every living organism consists of living cells and each cell has a set of organic structures called chromosomes.

I know, human cells have 23 pairs of chromosomes … and in each cell, the chromosomes are identical to each other. But what are these chromosomes ?

Yes there are 23 distinct chromosomes in each human cell and since there are two copies of each chromosome, we have 23 pairs.

I know, one acts as redundant backup copy in case one get damaged.

There is a huge science and technology around genetics and the study of the genome but we shall ignore that at the moment and focus on what matters most – the sequence.

Why is this sequence so important ?

Let us assume for the time being that the genome is a “book” and this book is written using an alphabet consisting of just four letters, namely A, C, T, G. This book has 23 “chapters” and each chapter has approximately a thousand “stories” and these are called genes.

A continuous set of one thousand stories ?

Not continuous .. the stories consists of meaningful “paragraphs” – called exons – and these interspersed with junk, or irrelevant sequence of letters, like advertisements in a magazine that are called introns. Finally each paragraph, whether a meaningful exon or an inexplicable intron consists of “words” called codons.

Rather complex

True but not the bottom of the hierarchy. Remember there are only 20 kinds of codons – or 20 “words” in this vocabulary, and as we said earlier, there are only 4 letters in the alphabet – A C T G.

What is this A C T G, obviously these are not the letters of the English alphabet.

Of course, but as you would realize shortly, for our analysis they just might be but do not panic as yet. The letter A C T G are used as a short hand for four specific organic molecules namely, Adenine, Cytosine, Thiamine and Guanine … and what is remarkable is that all living organisms that we know of at the moment use the same four ‘letters’ or bases, irrespective of whether it is human being or a bacteria living in the middle of a volcano !

So the sequence that you were referring to were sequences of these molecules.

Yes, it is as if these molecules ( A / C / T / G ) were strung together, like “letters” of the alphabet, in a specific sequence to form first codons, or “words”, which are then strung together to form exons, or “paragraphs”, which in turn are strung together to form genes, or “stories”.

Is this the DNA ?

DNA is long chemical molecule that acts as the thread on which the A C T G molecules are placed to form the sequence. If A C T G are flowers in a garland, then DNA is the thread on which the flowers are placed. Of course, unlike garlands, the DNA molecules do not loop back on themselves – they are like linear or straight garlands.

And where are these DNA garlands placed ?

On one of 23 chromosomes – the so-called “chapters”. And these 23 chromosomes constitute the “book”.

But what does this “book” contain, what are these so called “stories” about ?

These stories are actually “recipes” but before I start on that, remember I talked of two kinds of sequences, the genotype and the phenotype.

Yes and you have just described the genotype, what about the phenotype ?

We say that than organism is alive if and only if it has a class of molecules called proteins and it is these proteins that are referred to as phenotype. A protein molecule gives us shape, size, colour, texture … it makes us what we are – human beings and not birds or reptiles, who have their own kinds of proteins. Significantly, it is these proteins when in the company of thousands of other proteins that gives living organisms the basic ability to eat, to see, to grow, to hear, to talk, to think and to do all that is necessary to actually live.

So it is this phenotype, this collection of protein molecules that collectively give us what is known as life ? But what exactly is a protein anyway …

Now if you take a protein and look carefully you will see that it too is a sequence of smaller molecules … these molecules are called amino acids … and once again, there are only 20 of them.

I thought that there were 20 codons.

I will come back to that in a moment but for the time being let us focus on the 20 amino acids and we will note that it is the same 20 amino acids that are present in the proteins of all living organisms that exist today or have existed in the past … from human beings to the dinosaurs.

Nature is indeed very economical with its basic materials – only 4 bases or letters are used to build the genotype and only 20 amino acids are used to build the phenotype.

Yes … and the magic is that the 4 bases – A C T G – that form the genotype are found in only 20 different combinations – the codons, or “words” – in the genotype and there is a one-to-one correspondence between a codon and an amino acid.

What does this one-to-one correspondence mean ?

Aha … you had asked what is it that the “book” contained ? what are the “stories” about .. and I had said that the genome was a recipe book and each story was indeed a recipe.

Yes .. but where is the linkage ?

The recipes in the genotype, the genes, are used to assemble the proteins of the phenotype.

You mean each gene corresponds to a protein.

Yes … each gene – which is one specific sequence of A C T G arranged on a particular stretch of a DNA molecule -- carries information but is not capable of any metabolic function. The information in each gene is used to create a specific protein molecule – by mapping the codons on the gene to the amino acid required for the protein – and it is this protein, which gives rise to the physical appearance or metabolic function of a living organism.

So the genotype – consisting of thousands of genes, has the information to create the phenotype – consisting of proteins, that give rise to life and metabolism.

Right and some of these proteins, have the ability of create other proteins and this includes, in addition to other proteins, the DNA itself and that is used in the next generation.

So the genotype and the phenotype is very closely related to each other ? But how exactly does all this happen ? How is the information in the genotype used to create the phenotype ? And how does the phenotype create further instances of the genotype for the next generation ?

The exact process[2] is a matter for molecular biologist, we are not interested in that right now, but believe me a process exists and it is reasonably well understood. For us, we need to know only the Central Dogma of molecular biology.

This is intriguing.

Certainly it is, especially if you consider the following :
* Protein – the ability of the organism to perform actual action is the phenotype
* Gene – the knowledge of how to perform an action is the genotype

and this has an uncanny resemblance to the duality of the Shiva Shakti paradigm. Shiva is knowledge but is incapable of action unless it is coupled with the Shakti the active principle.

Are you saying that they are one and the same ?

Not so fast ! We need to look closer at the persistent Gene

[1] For a more comprehensive insight into this subject, please refer to Genome, Matt Ridley, HarperCollins, ISBN 0-06-019497-9

[2] The exact process is called Transcription. Any standard textbook of genetics or molecular biology will explain this in great detail.

No comments: