Biology Reference
In-Depth Information
mRNAs—miRNAs are thought to have a broad impact on the gene
regulatory networks that orchestrate mammalian physiology.
The evolutionarily oldest, most conserved miRNAs are commonly
expressed at the highest levels and alterations in their concentrations often
result in distinct phenotypes (
Johnnidis
et al
., 2008
;
Klein
et al
., 2010
;
Lu
et al
., 2008b, 2010
;
Patrick
et al
., 2010
;
Rodriguez
et al
., 2007
;
Thai
et al
.,
2007
;
Ventura
et al
., 2008
;
Xiao
et al
., 2007
). Alternatively, younger
miRNA families are commonly expressed at much lower levels and have
a higher probability of being lost during evolution (
Lu
et al
., 2008b
). In
these cases, it has been hypothesized that newly evolved miRNAs might be
substrates for the formation of new regulatory circuits. If this new interac-
tion is advantageous, a new miRNA and target mRNA connection can
become fixed. Because the miRNA “seed” interaction with a cognate
mRNA 3
0
UTR only requires 7-8 nucleotides to become functional, acqui-
sition of such sites due to spontaneous mutations within an mRNA's
3
0
UTRs should happen more often than changes that require a longer
sequence alteration (
Shomron
et al
., 2009
).
The hematopoietic system has a fascinating evolutionary history marked
by the seminal event of the acquisition of adaptive immunity when the jawed
fishes evolved (
Cooper and Alder, 2006
). Over evolutionary time, one can
see a positive correlation between the number of miRNAs expressed by
different organisms and their phenotypic complexity (
Peterson
et al
., 2009
). It
is thought that transcriptional noise, which varies in the expression of specific
genes within a given cellular population, must be limited in order to allow for
stable, complex phenotypes to take shape (
Hornstein and Shomron, 2006
).
Through their ability to regulate mRNA concentrations posttranscription-
ally, miRNAs are well suited for this job. In fact, mRNAs with conserved
3
0
UTR miRNA binding sites are expressed at more comparable levels
between species than mRNAs without miRNA sites (
Cui
et al
., 2007
).
As an aside, one might expect that quantitative control of the expression
of genes would be regulated by transcriptional modulation. That certainly
happens, but it may be that the evolutionary fine-tuning of gene transcrip-
tion is difficult, perhaps partly because of the inherently cooperative nature
of transcription due to the multiple transcription factors that control single
genes through established binding site motifs. Thus, miRNAs may have
evolved because of their ability to provide finer regulation than is conve-
niently achieved at the transcriptional event.
2.2. MicroRNAs fine-tune gene expression levels in the
hematopoietic system
There are more than 100 different miRNAs expressed in the hematopoietic
system (
O'Connell
et al
., 2010a
). A recent study investigated the types of
protein-coding genes that are predicted to be regulated by immune system
