Mouse synteny

1. Synteny between the mouse and human genomes

Alec MacAndrew

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.

Synteny

Synteny between species means not only that orthologous (functionally and ancestrally identical) genes are present but that they are present in the same order on the genome, thus indicating common ancestry.

The sequencing of the mouse genome and its comparison with the previously sequenced human genome reveals that 90.2% of the human genome and 93.3% of the mouse genome lie in conserved syntenic segments. These segments consist of 217 conserved syntenic blocks with an average length of 23.2Mb (23.2 million bases) So not only do we find homologous sequences between the two genomes; the genes actually lie on the chromosome in the same order. This is powerful evidence for common ancestry. It is possible to dismiss homology as arising from similar function, but it is not possible to dismiss synteny this way.

The detail is fascinating: The X-chromosomes of mouse and man are represented as single syntenic blocks. A portion of mouse chromosome 2 makes up the entirety of human chromosome 20. A portion of mouse chromosome 11 makes up the entirety of human chromosome 17, but the genetic material has been broken up into 16 separate segments.

It is not surprising that syntenic segments are rearranged within chromosomes. Inversions within a chromosome (that is where the DNA material is inverted or reversed due to a mutation - there is a famous inversion on the X-chromosome between Pan and Homo) have a low selective disadvantage.

There is a very important finding: analysis of the size of syntenic blocks is consistent with the random model of genome evolution: in other words the frequency with which different lengths of conserved syntenic sequence appear points to a random mechanism for inversion and translocation.

Analysis also indicates that a minimum of 295 rearrangements is necessary to account for the syntenic map between mouse and human. That would indicate one major chromosomal rearrangement about every 200,000 years. With only two mammals sequenced it is not possible to recover the ancestral arrangement of the syntenic genomic material in the ancestor of all mammals. However, the sequencing of more mammalian genomes will enable the recovery of the ancestral chromosomal order, and the very fact that this is possible points inexorably to common ancestry.