Initial sequencing and comparative analysis of the mouse genome

articlesInitial sequencing and comparative

analysis of the mouse genomeMouse Genome Sequencing Consortium**A list of authors and their affiliations appears at the end of the paper...........................................................................................................................................................................................................................The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key

experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality

draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes,

describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the

evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most

of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the

genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and

immunity; the evolution of proteins; and the identification of intraspecies polymorphism.With the complete sequence of the human genome nearly in hand1,2,

the next challenge is to extract the extraordinary trove of information encoded within its roughly 3 billion nucleotides. This

information includes the blueprints for all RNAs and proteins,

the regulatory elements that ensure proper expression of all genes,

the structural elements that govern chromosome function, and the

records of our evolutionary history. Some of these features can be

recognized easily in the human sequence, but many are subtle and

difficult to discern. One of the most powerful general approaches

for unlocking the secrets of the human genome is comparative

genomics, and one of the most powerful starting points for

comparison is the laboratory mouse, Mus musculus.Metaphorically, comparative genomics allows one to read evolutions laboratory notebook. In the roughly 75 million years since the

divergence of the human and mouse lineages, the process of

evolution has altered their genome sequences and caused them to

diverge by nearly one substitution for every two nucleotides (see

below) as well as by deletion and insertion. The divergence rate is

low enough that one can still align orthologous sequences, but high

enough so that one can recognize many functionally important

elements by their greater degree of conservation. Studies of...