Comparative Genomics
Comparative genomics is the analysis and comparison of genomes from different species.
The purpose is to gain a better understanding of how species have evolved and to
determine the function of genes and non-coding regions of the genome.
DNA sequence by itself, does not tell us directly how this genetic information leads to the
observable traits and behaviors (phenotypes). Comparative Genomics present a valuable
tool in resolving this problem.
When comparing genomes, we must consider the following: Sequence similarity, gene
location, the length and number of coding regions within genes, the amount of noncoding DNA in each genome, and highly conserved regions.
Model organisms offer many advantages, often including small genomes (with less
repetitive DNA) and well established genetic resources.
We focused on two ground-breaking researches which applied comparative genomics on
the well known S. cerevisiae and related species.
The first research, conducted by Manolis Kellis et al(i), used 3 yeast species of various
evolutionary distance in addition to S.Cerevisiae.
An alignment of the 4 genomes was accomplished by using the orthologous ORFs (open
reading frames) as “anchors”. An algorithm of several steps was established for
constructing subgroups of orthologs that maintain synteny.
After aligning all 3 additional genomes with the S.Cerevisiae genome, the genic as well
as the intergenic regions were compared at the nucleotide level in order to distinguish
functionality of genes, evolutionary rate, and for the search of regulatory elements.
The research resulted in wide changes of the annotation of the S. cerevisiae genome
includig the cancellation of 503 (previously annotated) genes and discovery of 43 new
genes. 58 new introns and 42 new regulation motifs were identified. In about 500 genes a
new location was discovered for start or stop codons.
A supplementary article(ii) describes in depth all stages of the algorithm of finding
orthologues ORFs in the 4 yeast species. It also presents the intricate methods of the
discovering of new regulatory motifs.
The Second research, conducted by Audrey Gasch et al(iii) examined 14 Ascomycete
Fungal species. The research focused on the evaluation of the conservation and evolution
of cis-regulatory systems. An element is defined cis-regulating when it regulates the
transcription of an adjacent gene on the same chromosome through binding of
transcription factors. While closely related species allow alignment of non-coding
sequences where putative cis-regulatory elements can be identified and compared, more
distant species are too divergent in their regulatory regions. Thus the research’s guideline
was to construct groups of co-regulated genes that contain common regulatory sequences
in S.Cerevisae and independently examine the common regulatory sequences in their
orthologues in 13 other yeast species.
The authors believe that most genes that are co-regulated in S.Cerevisiae are also coregulated in other species. However a lesser conservation within the regulatory systems
may point to evolutionary processes and enlighten morphological and functional
differences between species.
It has been concluded that conservation in regulatory systems occur even in evolutionary
distant species. The conservation predominates in sequence and general localization.
Nevertheless, evolution of regulatory systems can be noticed through modification of
existing sequences, appearance of new regulatory sequences, reappearance of old
sequences in new locations and a shift of an existing regulatory system to regulate
different genes.
In conclusion, as sequencing technology evolves, comparative genomics will gain power,
and will likely become a common tool in order to shed light on biological problems.
i
Kellis M, et al. (2003) Sequencing and comparison of yeast species to identify genes and
regulatory elements. Nature 423: 241–254
ii
Kamvysselis M, et al. (2003) Whole-genome Comparative Annotation and Regulatory
Motif Discovery in Multiple Yeast Species. ACM Recomb-03' proceedings.
iii
Gasch AP et al. (2004) Conservation and evolution of Cis-Regulatory systems in
Ascomycete fungi. PloS Biol. 2:e-398