Biology Reference
In-Depth Information
differences to the level of molecular systems such as pathways, regulatory
networks, and macromolecular complexes.
The availability of whole-genome-scale data provides the opportunity
to identify the complete set of functional elements, and hence enables the
recognition not only of what is present but also of what is absent from
the genomes. This is an essential basis for many comparative techniques,
for example, to decipher gene genealogies (orthology). A prerequisite,
therefore, to higher-level comparative studies is the comprehensive anno-
tation of genomes for genes and pseudogenes, both protein-coding and
non-protein-coding RNAs, regulatory binding sites, conserved non-
coding sequences, and repetitive elements. Conversely, comparative
approaches provide evidence of evolutionary selection to guide the refine-
ment of genome annotations. Thus, the two approaches are inextricably
linked, as recently exemplified by the pilot ENCODE (ENCyclopedia Of
DNA Elements) project
1
and the analysis of 12
Drosophila
genomes.
2,3
Although many basic biological processes are similar between
human and model organisms, the detailed biology becomes less compa-
rable between more distantly related organisms. It is therefore impor-
tant to not only develop the understanding of the models as thoroughly
as possible, but also establish the common basis and recognize the line-
age-specific biology to make informed inferences regarding gene func-
tions and to translate the research into new methods for maintaining
human health and for diagnosing and treating diseases. As sequence data
continue to be generated at an ever-increasing rate, the power of com-
parative analyses to illuminate evolutionary processes on a genomic scale
and to facilitate the
de novo
discovery of functional elements character-
ized by specific evolutionary signatures is also growing. At the same
time, comparative genomics methodologies continue to evolve and
develop, with analytical approaches aimed at different levels of species
relatedness, from deep evolutionary phylogenies to genomic variations
within a population.
2. Gene Annotation
Despite the RNA origin of life, in modern organisms proteins are often
considered chiefly responsible for biological function, and therefore
