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What does the mouse genome draft tell us about evolution?

Alec MacAndrew

Click on the links below to explore various aspects of the mouse genome,  its comparisons with the human genome and the consequences for evolutionary thinking:


[Mouse synteny][Mouse repeats][Mouse gene][Mouse protein][Mouse genome mutation and selection]



The draft mouse genome was published on 6th December 2002 , Waterstone et al, Nature 420, 520 - 562

Note that this is a 43 page paper (Nature averages 2 -3 pages per paper) with around 200 authors and 330 references. This is all new to science and the volume of material is more than a very fat text book if one includes the references . The detail is published not in a single paper, but in about six related papers occupying more than half of the super fat 6th December issue of Nature.

Scientists think that the mouse genome will be even important than the human genome to medicine and human welfare. That seems bizarre: why is that? The reason is that, because of the relatively 'recent' divergence of the mouse and human lineages from our common ancestor (about 75 million years ago), an astonishing 99% of mouse genes turn out to have analogues in humans. Not only that, but great tracts of code are syntenic - that means the genes appear in the same order in the two genomes.

Since we can experiment on the mouse genome (we obviously cannot do that with people), the mouse will be a hugely valuable model to understand the function and operation of the genetic machinery in people. We already have incredibly precise tools to modify the mouse genome including the ability to delete or duplicate extensive tracts of code, the ability to knockout or knock-in single genes and even the ability to make single base substitutions.

The astonishingly close homology that has been revealed in the code between mouse and human genome extends to functionality. Many homologous genes have identical functions in the two species, anatomy, physiology and metabolism are similar and genetic disease pathology can be very similar. So the fact that we can study the mouse empirically, means that we can identify the functions of genes in people and both understand human disease pathology and create ways to treat it.

One example, given in the accompanying News and Views article in the same edition of Nature, is that the same genetic defect causes cystic fibrosis in humans and a similar disease in the mouse, except that in the mouse it does not lead to the most debilitating aspect of human cystic fibrosis which is lung disease. By understanding how the mouse avoids contracting lung disease in the presence of this genetic lesion, we could well find a way to prevent the development of lung disease in human cystic fibrosis sufferers.

Another interesting finding is a surprising level of conservation in certain tracts of non-coding sequence (so-called junk DNA). It seems that some of this material does have some (probably regulatory) functionality and that there is more of this than we thought. (Not all of course is conserved - there is still a huge amount of junk that can be regarded as genetic fossils).

Click on the links below to explore various aspects of the mouse genome,  its comparisons with the human genome and the consequences for evolutionary thinking:

Human Mouse synteny

Synteny occurs when similar genetic code occurs in the genomes of two species in the same order

Sequence repeats - the repeats in human and mouse compared

Sequence repeats are the result of insertions of genetic material by retroviruses etc

Comparison of the genes of human and mouse

Concentrating on the sequences coding for proteins

Comparison of human and mouse proteins

Concentrating on the proteins themselves

A look at mutation and selection in mouse and human genomes

The basic mechanism of evolution are mutation and selection - what do the mouse and human sequences tell us?

Evidence for the Theory of Evolution

The findings of the draft mouse genome are astonishingly powerful evidence for common ancestry, mutation and selection: in short for the Theory of Evolution. There is a list with links below for the key points within the paper which can only be explained by evolution.  It is just not possible to explain what we see in the two genomes if they have only been in existence for 6500 years unless we invoke deliberate deceit on God's part:

     90.2% of the human genome and 93.3% of the mouse genome lie in conserved syntenic segments - go here


     The syntenic blocks have been re-arranged by chromosomal events over time - go here


     The distribution of size of the syntenic blocks is consistent with a random mechanism for chromosomal rearrangements - go here


     It is possible to recognise the difference between repeat sequences that were added to the genomes before divergence of mouse and man lineages and those added after divergence - go here


     The measured mutation rate since divergence of mouse and man is ample to explain the divergence of the species - go here


     The rate of insertions of repeat sequences as a function of time can be measured for both man and mouse - go here


     Repeat sequences are tolerated in the same regions in mouse and man and in both cases insertion of repeat sequences is not tolerated in functionally critical regions such as the homeobox clusters - go here


     Two sorts of pseudogene exist in eukaryotes - processed and unprocessed - we know how they arise and it has taken millions of years for the pseudogenes we see in mouse and man to arise - go here


     Pseudogenes can be identified by the ratio of synonymous to non-synonymous mutations occurring over millions of years and by the fact they do not generally have a homologous gene in the same syntenic position in the other genome - go here


     99% of mouse genes have homologues in humans and 96% are in the same syntenic location - go here


     The fact that mouse and human are relatively closely related allows us to study orthologous genes - genes which have arisen and diverged from a common ancestor - go here


     12,845 orthologous gene pairs were found between man and mouse (homologous genes in the same syntenic  location) - go here


     The Ka/Ks ratio (ratio of non-synonymous to synonymous mutations is = 1 in neutral regions and the median value is 0.115 in genes) - this can only be explained by common descent - go here


     Within genes, regions containing known domains have a lower Ka/Ks ratio than those that do not - go here


     The percentage of cases in mouse where the mouse gene matches the most common human allele at sites which have Single Nucleotide Polymorphisms is very close to the percentage of amino acid identity across the two genomes: very strong evidence for common ancestry - go here


     Expansion into gene families has occurred in cases where the family has important functionality specific to a lineage - go here


     The Ka/Ks ratio in lineage specific gene families is higher than average suggesting that they are undergoing more rapid evolution than the rest of the functional genome as evolution theory would predict - go here


     The percentage nucleotide alignment across the whole of the mouse and human genomes (about 40%) is compatible with what is known about the rate of DNA deletion in the two lineages since divergence - go here


     The rate of substitutions in ancestral repeat sequences in non-coding DNA is the same as the rate of substitution at four fold degenerate sites in functional regions - very strong evidence for mutation and selection over a long time - go here


     The detail of which parts of the genome are more highly conserved between the two species aligns well with functionality - go here


     Introns are conserved no more than background non-functional DNA and so do not appear to have functionality in their code - go here


     Gene structures - number of exons and coding length in exons - is strongly conserved across mouse and human genomes - very strong evidence for common ancestry - go here


     The difference in mutation rate (obtained by comparing mouse and human genomes) between X-chromosomes and autosomes can be explained by what we know about differences in mutation rate in male and female meiosis and relies on common ancestry and mutation over millions of years - go here



[Mouse synteny][Mouse repeats][Mouse gene][Mouse protein][Mouse genome mutation and selection]
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