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RTD info logoMagazine on European Research Special Issue - April 2005   
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BIOLOGY
Title  DNA, life’s memory

To reconstruct past events, journalists can turn to witnesses, historians to the archives and biologists to… DNA. The hundreds of millions of chemical letters that make up the genome sequence retain – for anyone able to read it – the memory of the evolution that led to the appearance of the species.

Linus Pauling. This two-time Nobel prizewinner, the ‘father’ of the molecular clock – whose theory is today contested – revolutionised the history of life and offered a new slant on evolutionary concepts.   © Dick Willoughby - Linus Pauling Institute
Linus Pauling. This two-time Nobel prizewinner, the ‘father’ of the molecular clock – whose theory is today contested – revolutionised the history of life and offered a new slant on evolutionary concepts.
© Dick Willoughby - Linus Pauling Institute
Linus Pauling (1901-1994) is a member of that very select club of two-time Nobel Prize laureates. In 1954, he received the Nobel Prize for chemistry for his work on the covalent link and, in 1962, his campaigning for nuclear disarmament won him the Nobel Peace Prize. It is due to the sheer brilliance of his career that one sometimes forgets that this all-round genius is also the founder of molecular phylogeny, a discipline that seeks to decipher the history of life by studying some of the molecules of which it is composed.

From the mid-1950s, Pauling became interested in the chemistry of proteins and was one of the first to regard amino acids as the ‘building blocks’ of life. He subsequently described their arrangement in a protein (haemoglobin) in a number of vertebrate species. He was surprised to find that the number of differences between the amino acids in each species pair was proportionate to the time that separates them from their common ancestor. Together with his colleague Emile Zuckerandl, Pauling formulated the notion of the molecular clock, in 1965, postulating that the degree of divergence between two amino acid sequences is constant throughout evolution. This hypothesis was to revolutionise the history of life as, for the first time, it became possible to evaluate the divergence time for species for which there are no fossils.

The age of the molecular clock
Pauling’s innovative approach did not bring any immediate rewards because the data on the protein sequence were many, lengthy and difficult to obtain. All this changed in 1977 when the British researcher Frederic Sanger – another member of the two Nobels club – developed a method for rapid DNA sequencing. Aided by robotisation and automation, a wealth of data was soon available to molecular phylogeneticians who then looked again, with new tools, at the eternal question of the history of life. Their hypothesis was the following: mutations accumulate at a comparable speed between two distinct species subject to an equivalent selection pressure. By comparing the sequences for these genome regions in different species, it must therefore be possible to identify and quantify the differences that are the basis on which their divergence can be located in time. What is impossible when one looks at the filiation of an individual – who possesses just one quarter of the genes of each grandparent, an eighth of each great grandparent, and so on – becomes possible in terms of a species. 

DNA is the molecular basis of heredity. In this model cross-section, the various atoms are represented by different colours: carbon in orange, oxygen in blue, nitrogen in red,hydrogen in white, and phosphorous in violet. On the right, view of the horizontal axis of the helix. © INSERM/J.L.Martin/J.C.Lambry
DNA is the molecular basis of heredity. In this model cross-section, the various atoms are represented by different colours: carbon in orange, oxygen in blue, nitrogen in red, hydrogen in white, and phosphorous in violet. On the right, view of the horizontal axis of the helix. © INSERM/J.L.Martin/J.C.Lambry
DNA is the molecular basis of heredity. In this model cross-section, the various atoms are represented by different colours: carbon in orange, oxygen in blue, nitrogen in red, hydrogen in white, and phosphorous in violet. On the right, view of the horizontal axis of the helix.
© INSERM/J.L.Martin/J.C.Lambry
This assumption led to a refining of the notion of the molecular clock by distinguishing three levels. First, there are the evolutionary seconds that are the hundreds of thousands of years which researchers study on the basis of genome regions where mutations accumulate rapidly. This is the case of pseudo-genes, sequences that resemble genes but which are not expressed and, thus, not subject to much selection pressure. With this second hand, it is possible to date divergences among sub-populations within a single species. Next, come the minutes that are the millions of years of a still close past. By studying the gene coding of proteins with a vital role, such as haemoglobin, it is possible to date divergences between species. Finally, to unlock the hours – that is the tens of millions of years during which entire species separate – scientists revert to proteins subject to very strong functional constraints, such as histones that link up with DNA to permit its breakdown into chromosomes.

Reclassifying life
Carl Woese was a pioneer of this approach. In 1977, he showed, by studying ribosomal RNA sequences, that life does not divide into cells with a nucleus (eukaryotes) and without a nucleus (prokaryotes), but into three groups separated by genetic divides: archaebacteria – the oldest, still living today in extreme environments, such as the seabed and hot springs –, eubacteria and eukaryotes. At the same time, a conceptual revolution in biology, phylogenetic systematics, called into question the principles according to which life had been classified by Linné in the 18th century. Scientists were beginning to doubt the pertinence of groups regarded as fundamental, such as fish or reptiles.

However, in the late 1980s, the notion of the molecular clock was severely criticised. The DNA clock has neither the precision nor the regularity of a Swiss cuckoo clock. During certain periods, or in certain regions of the genome, mutations are more frequent, as if a mysterious clocksmith had advanced the minute hands. This deregulator could be a virus inserting its genome into that of the host, or a recombining event between chromosomes at the time of cellular division. Over long periods, the clock slows and becomes imprecise, like a mechanism that needs rewinding.

During the 1990s, phylogeneticians learned to take these phenomena into account and a whole new vision of the history of life gradually emerged. The former groups of algae or invertebrates were set aside, as they did not correspond to any difference in terms of DNA. Mammals were not spared either: the cetaceans were found to be cousins of the hippopotamus, as an examination of their morphological characteristics by phylogenetic systematics had already suggested. The combination of a conceptual revolution – phylogenetic classification – and a technological revolution – the comparison of sequences made possible by this surprising conservation of the evolutionary memory in DNA sequences – resulted in the entire classification of life being revised over a period of some 30 years, after having remained virtually fixed since Linné’s day. 


Printable version

Features 1 2 3 4 5
  Science is embedded in culture and history
  Inside the memory machine
  DNA, life’s memory
  The nuts and bolts of remembering
  From forgetfulness to dependency

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The geneticians’ bestiary

To study animal memory, biologists use protocols that often have recourse to the associative memory, distant derivatives of the protocol used by the Russian physiologist Ivan Pavlov and his famous dog. The drosophila, the species ...
 

  TO FIND OUT MORE  
 

Some European molecular phylogeny projects
  • Origin of biodiversity: molecular phylogeny of copelatinae, a megadiverse group of diving beetles
    Contact: Alfried Vogler
  • Paleontological ...
  •  


       
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    Features 1 2 3 4 5


    The geneticians’ bestiary

    To study animal memory, biologists use protocols that often have recourse to the associative memory, distant derivatives of the protocol used by the Russian physiologist Ivan Pavlov and his famous dog. The drosophila, the species of fruit fly so popular with geneticists, is presented, for example, with two tubes containing different odours. When it visits one of the tubes, it receives an electric shock and quickly learns to recognise the tube and odour that cause it no harm. By repeating the test at intervals of a few days or few hours, it is possible to distinguish two phases in any memory process: the initial phase, characterised by a short-lived and fragile storage of information, and the consolidation phase that permits lasting storage. In the drosophila, geneticists have given somewhat amusing names to the genetic mutations that are able to interfere with one or other of these phases. The ‘dunce’ mutation changes the short-term memory and the ‘crammer’ mutation disturbs the long-term memory. 

    Do these genes have equivalents in mammals? None has been found to date. On the other hand, another gene, one that encodes a protein known as CREB (Camp Responsive Element Binding), is involved in encoding the long-term memory of virtually all living creatures in which it has been studied: the aplasia, a marine snail, that learns to withdraw its gills in response to a stimulation of its siphon, rather like one pulls back one’s hand on contact with something hot; the drosophila; the mouse, in a test developed by Scotsman Richard Morris of Edinburgh University, that learns to find a platform immersed in a swimming pool; and finally humans’. It is therefore hardly surprising that the pharmaceutical industry is very interested in this CREB protein in which it hopes to find a remedy for Alzheimer’s disease or, perhaps even, a stimulant for students revising for their exams.

    CREB protein
    CREB protein

    TO FIND OUT MORE

    Some European molecular phylogeny projects
    • Origin of biodiversity: molecular phylogeny of copelatinae, a megadiverse group of diving beetles
      Contact: Alfried Vogler
    • Paleontological and molecular approaches to the phylogeny of acanthomorpha (pisces)
      Contact: Guillaume Lecointre
    • Molecular phylogeny of mammalian orders: a model study
      Contact: Wilfried de Jong

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