MicroRNAs Have Shaped The Evolution Of The Majority Of Mammalian Genes

MicroRNAs Have Shaped The Evolution Of The Majority Of Mammalian Genes: "In a paper published last January in the journal Cell, Bartel's lab, in collaboration with Chris Burge's lab at MIT, presented evidence that one third of human genes are regulated by microRNAs. In this new study, published online Nov. 24 in Science, the researchers demonstrate that microRNAs affect the expression or evolution of the majority of human genes.

Nearly all genes, the authors explain, contain short sequences that match portions of microRNAs. Some of these potential microRNA target sites are evolutionarily "conserved," meaning that they show up in the same spot on the same gene across species as disparate as the mouse and the chicken. The authors of last January's Cell paper showed that thousands of human genes contain microRNA sites that are conserved in this way. To the extent that evolution has preserved these sites more than would be expected by chance, scientists have regarded them as sites that microRNAs target.

In the new study, scientists in the Bartel lab designed an experiment that zeroed in on these nonconserved targets. Grimson took mRNAs whose target sequences were not conserved and exposed them to microRNAs, which latched on without a problem. The experiment proved that a matching sequence is generally sufficient to disrupt mRNA's ability to make protein.

Kyle Kai-How Farh, a graduate student in Bartel's lab, found that mRNAs with nonconserved sites were generally absent in cells with corresponding microRNAs--more absent than statistical models suggested. The researchers concluded that over the course of evolution many mRNAs, in order to maintain their functions and ensure fitness of the organism, have quickly lost sites that pair up with microRNAs.

In addition to the thousands of cases where genes have avoided microRNA targeting, Farh also investigated the opposite extreme, cases where genes have maintained microRNA target sites over the course of evolution. He found that as immature muscle cells stop dividing and become mature muscle cells, microRNAs are activated and suppress genes that are no longer needed at such high levels in the mature muscle. "Many of these evolutionarily conserved microRNA targets are known to be active in the processes of cell proliferation, development, and cancer," says Farh. "Our genomes have good reason to maintain the microRNA targeting sites necessary for turning down these genes at the appropriate place and time."

An emerging idea is that microRNAs often act to reduce the quantity of protein a gene produces without shutting it off all together. "We think the microRNAs are sometimes having what you can call a dampening effect," says Bartel, who is also a Howard Hughes Medical Institute investigator and MIT professor of biology. "They appear to be helping cells achieve optimal levels of proteins.""


Blogger qtr said...

Glossary of terms: classification systems and population mechanisms in speciation:

Allopatric speciation occurs when a geographical barrier sub-divides a parent species, resulting in geographic and reproductive isolation such that the descendent species can no longer interbreed upon removal of the barrier.

Anagenesis differs from cladogenesis in that one species progressively transforms into a replacement species when sufficient gene mutations fix in the descendant population. At this point, the ancestral species has become extinct. This mechanism is distinct from the increase in numbers of species generated by cladogenetic branching events.

Cladogenesis is the mechanism of speciation in which one or more lineages (clades) arise from an ancestral line. Such speciation events increase the variety of plants or animals through branching of the phylogenetic tree. Cladogenesis is differentiated from anagenesis, which is the in toto replacement of one species by an anatomically distinct species.

Monophyletic taxon or clade: an accurate grouping of only (opp. polyphyletic) and all (opp. paraphyletic) descendents of a shared common ancestor. A monopyletic group is genetically homogeneous and reflects evolutionary relationships.

Paraphyletic taxon or clade: a monophyletic group that excludes one or more discrete groups descended from the most recent common ancestral species of the entire group. Other descendent species of the most recent common ancestor have been excluded from the paraphyletic taxon, usually because of morphologic distinctiveness.

Phenetic system: groupings of organisms based on mutual similarity of phenotypic (physical and chemical) characteristics. Phenetic groupings may or may not correlate with evolutionary relationships.

Phylogenetic system: groups organisms based on shared evolutionary heritage. DNA and RNA sequencing techniques are considered to give the most meaningful phylogenies.

Phylogenetic separation into evolutionary relationships (clades), based on comparison of genomes is likely to supplant phenotypical (phenetic) taxonomies of the prokaryotes.

Peripatry (paripatry) is a subset of allopatry in which an isolated group has a smaller population than the parent group. Ernst Mayr introduced the term. Peripatric speciation occurs when the smaller sub-group of a species enters a novel niche within the range of the parent species, becoming geographically and reproductively isolated. Peripatric speciation (paripatric) is distinguished from allopatric speciation by the smaller size of the isolate group, and from sympatric speciation, which involves no barrier to breeding.

Polyphyletic taxon: opposite to monophyletic taxon: A polyphyletic group is mistakenly or improperly erected on the basis of homoplasy — characteristics that have arisen despite not sharing a common ancestor. Homoplasy arises because of convergent evolution, parallelism, evolutionary reversals, horizontal gene transfer, or gene duplications. Polyphyletic taxa are genetically heterogeneous because members do not share a common ancestor.

Neontology is a branch of biology that emphasizes the study of modern biota (living or recent organisms) rather than fossilized organisms (paleontology).

Numerical Taxonomies are a common approach to phenetic taxonomy that employ a number of phenotypic characteristics to generate similarity coefficients that may be mapped in dendrograms. Groupings based on numerical taxonomy may or may not correlate with evolutionary relationships.

Taxonomies aim to group organisms according to shared characteristics against the background of biological diversity.

Sympatry involves no geographical separation of sub-populations of individuals. Sympatric speciation events occur most often in plants by the mechanism of polyploidy in which the number of chromosomes is doubled or tripled. John Maynard Smith proposed a model called disruptive speciation, in which homozygotes might have greater fitness than heterozygotes under some environmental conditions.

10:45 PM  

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