Comparative Genomics-Basic and Applied Research.pdf

4 Comparative Genomics
HGT is now recognized as a major force in not only the evolution of prokaryotes but
also the emergence of the eukaryotic cell. Considerable evidence exists for ancient
HGT involving the transfer of genes from putative bacterial endosymbiont ancestors
of organelles, namely, mitochondria and chloroplasts, to the eukaryotic host nuclear
genome. Some groups of single-cell eukaryotic protists, such as Apicomplexa, which
includes the human malarial parasite Plasmodium falciparum, evolved from multiple
endosymbiosis and engulfment events (for review, see Brown 23 ). The extensive
occurrence of potential HGT events has challenged the concept of species classification
for prokaryotes as well as the prospects for reconstructing a universal tree of
life. 24,25 Comparative genomics has shown HGT to be, at the very least, a potentially
significant mechanism of genome modification with an impact on nearly all species
at some point in their evolutionary history.
1.3 NOT-SO-JUNK DNA
Genes encoding proteins and RNAs, such as ribosomal and transfer RNAs, were traditionally
thought to be the key functional elements of the genome. While regulatory
elements in noncoding DNA such as promoters and enhancers were recognized as
crucial, other noncoding regions of DNA were thought to be “space fillers” or traps
for selfish, parasitic DNA segments such as transposons. However, this so-called
junk DNA has been shown to control critical cellular functions largely through the
application of comparative genomic analyses. High-density tiling DNA arrays have
revealed that most of the human genome is actively transcribed, even non-proteincoding
regions. 26, 27 Studies have unveiled the critical roles that RNAi mediated by
small noncoding RNAs (ncRNAs) play in the regulation of eukaryotic genes. A particular
important ncRNA class is microRNA (miRNA), single-stranded, 19- to 23-
nucleotide long RNAs that repress translation by binding to specific messenger RNA
target sites. The miRNA were first discovered in C. elegans but subsequently were
found to be widespread throughout metazoans. 28 The miRNAs differ from short
interfering RNAs (siRNAs) in that they are derived from single-stranded rather than
double-stranded RNA precursors. Yet, like siRNAs, miRNAs can under some circumstances
also effect messenger RNA degradation and generally share a common
route to biogenesis. Computational predictions of miRNA genes and their target sites
suggest that most metazoan and plant genomes encode at least several hundred, if
not thousands, of miRNA genes, and that a large proportion of protein-coding genes
have putative miRNA regulatory binding sites (reviewed in Brown and Sanseau 29 ).
Many crucial cellular processes are regulated by miRNAs, including tissue morphogenesis
30 and metabolic pathways. 31 The miRNAs are also implicated in various
disease pathologies, including cancer 32 and host–virus interactions. 33
Other ncRNAs have been discovered, particularly a novel class of small RNAs
isolated from mouse testis libraries; these ncRNAs are called PIWI-interacting
RNAs or piRNAs based on their processing proteins. 34,35 The piRNAs are encoded
by specific genomic regions, also conserved in rat and human, and appear to play
a role in the suppression of transposon activation. 36,37 These exciting discoveries,
facilitated by comparative genomics, have unveiled an important mechanism of cellular
regulation by indigenous antisense RNAs.