Sunday, March 20, 2011

MicroRNAs Contribute to Lake Malawi Cichlid Diversity

Genetics of Adaptation Graduate Seminar
Author: Bethany A. Stahl

Cichlids are an amazingly diverse group of fishes that live in a series of rift lakes in SE Africa.  Rift lakes consistently experience water-level fluctuations that can temporarily form or breakdown isolation barriers of gene flow between adjacent populations.  As a consequence of isolation and rapid changes in the environment, species of cichlids have adapted a suite of unique morphological traits.  Adaptive characteristics can range from a mouth on the side of their head for feeding on scales of other fishes, to specialized jaws and teeth for feeding, and even range in color from blue-striped to black and spotted.  Since hundreds of these morphologically diverse species have evolved from a single common ancestor, they are an excellent model for investigating the genetic consequences of speciation (Loh et al., 2010).   

Though cichlid physical characteristics can vary significantly, their genomes are extremely similar (Moran and Kornfield, 1993; Loh et al., 2008).  Loh et al. (2010) suggested that microRNAs, molecules that “tinker” with the expression of RNA transcripts, may be the root of some of the observed cichild diversity.  The microRNA can act as a light switch to turn genes either on or off, or even a “mood-setting dimmer” to tone down the expression of a gene.  These elements are not part of the gene itself, yet play an important in the expression of physical traits.

Genes are composed of hereditary material termed DNA, and provide instructions for making the proteins that build the physical structures (phenotype) visibly seen in organisms.  Though genes seem to be the basic components leading to phenotype, additional regulatory elements play a role in gene expression.   Transcription factors are proteins that can regulate expression by binding to the enhancer or promoter regions of DNA located adjacent to the genes they regulate.   Similarly, miRNA functions in gene expression by targeting mRNA to repress or silence a gene, but differ from transcription factors in that they regulate genes after transcription has already occurred.

Loh et al. (2010) investigated miRNA as a potential target for phenotypic evolution.  They analyzed numerous cichlid sequences for the target region where the miRNA would normally bind to regulate the gene.  Comparisons were made between cichlids and other fish species.  Over 6,000 miRNA target sites were identified, and within these sites 1,002 SNPs were found.  Loh et al. (2010) further investigated the variation by mapping the substitutions to the physical locations within the genome and found that the predicted sequences fell within the 3’-UTRs – the region immediately downstream of a gene.  To determine the uniqueness of these sites within the 3’-UTRs, the sequences were compared to other fish genomes, which identified 130 sites exclusive to cichlids (Loh et al., 2010).  They also investigated sequences in the predicted miRNA targets across lineages and found that genetic diversity exists between groups of cichlid fishes (Loh et al., 2010).   In conclusion, Loh et al. (2010) described extreme genome similarity among cichlids, yet found numerous mutations among miRNA binding sites.

Though the data presented by Loh et al. (2010) is intriguing, how does it relate to questions of genetic evolution and species diversity?  Cichlids possess a highly similar genome and do not exhibit much variation within their genes, even when compared to zebrafish (Guryev et al., 2006).  Cichlid fishes experienced rapid changes in their aquatic environment, and isolation of populations have lead to a wide variety of morphological traits including color variation, feeding apparati, and breeding behaviors.  Diversity of cichlid traits has likely been accomplished through numerous changes in gene expression, including the action of miRNAs.  Loh et al. (2010) have identified over 100 distinct miRNAs unique to cichlids.  This number is likely to grow with further investigations since this is likely incomplete due to limited cichlid genome resources.  The sequence variation within the miRNA target sites suggests the miRNAs have experienced divergent selection in Lake Malawi cichlid species (Loh et al., 2010).

Loh et al. (2010) also identified one target site that is very similar between cichlids and stickleback fish.  This site is associated with a Hox gene, which is essential for fin-muscle development and regeneration.  Mutations in the miRNA sites related to Hox genes could be a mechanism underlying the observed  morphological variation in cichlid fishes.  Loh et al. (2010) suggests that other genes that may be affiliated with 3’-UTR binding sites and hope their data can help identify more interactions between miRNAs and genes.  

Clearly many complex elements contribute to gene expression and species diversity.  Genetic elements including genes and other regulatory  “switches,” such as miRNAs, contribute to phenotypic diversification.   When a species encounters a new environment, especially in cases when genes are highly conserved, evolution may be marked by alterations of these other regulatory elements to produce novel traits, potentially leading to adaptation.  miRNA diversity could be one of the numerous mechanisms targeted for changes in gene expression leading to a number of morphological features in cichlids.  As our knowledge of microRNAs and other factors contributing to gene expression expands, it will be exciting to see how it will change our perspectives of genetics of adaptation.

Guryev, V. Koudijs, M.J., Berezikov, E., Johnson, S.L., Plasterk, R.H., van Eeden, F.J., and Cuppen, E. 2006.  Genome Research. 16(4): 491-497.
Loh, Y.E.  2008.  Comparative analysis reveals signatures of differentiation amid genomic polymorphism in Lake Malawi cichlids.  Genome Biology. 9(7): R113.
Loh, Y.E., Yi, S.V., and Streelman, J.T.  2010. Evolution of MicroRNAs and the Diversification of Species. Genome Biology and Evolution. 3: 55-65.
Moran, P. and Kornfield, I.  1993. Retention of ancestral polymorphism in the Mbuna species flock of Lake Malawi. Molecular Biology and Evolution. 10: 1015-1029.
Won, Y.J., Sivasunder, A., Wang, Y., and Hey, J.  2005. On the origin of Lake Malawi cichlid species: a population genetic analysis of divergence. Proceedings of the National Academy of Sciences.  102: 828-837.

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