Photos of surface (top) and cavefish.

Blind Cavefish Genome Reveals Candidate Genes for Eye Loss

TGI researchers, alongside national and European collaborators, present the first de novo genome assembly for the blind cavefish. This genome may offer insights into analogous human diseases such as congenital abnormalities, retinal dysfunction, and sleep disturbances.

The study was published in Nature Communications on October 22nd, 2014.

Cavefish populations, Astyanax mexicanus, are subjected to strong environmental selection pressures and offer a window into understanding the genetic variants that contribute to evolutionary change. Found in northeastern Mexico, cavefish show repeated morphological evolution including eye degeneration, increased olfactory capabilities, and behavioral differences when compared to their surface counterparts. However, previous analysis of the cavefish genome was limited by the available reference- the zebrafish. In this study, researchers present the first de novo gene assembly for the cavefish.

This cavefish gene assembly draft size was 964Mb and researchers predicted approximately 23,000 protein-coding genes. Alignment of the open reading frames to the genome scaffolds showed a median of 81% of transcripts aligned over at least 75% of their length with at least 90% identity. From this assembly, it appears that a recent wave of transposition occurred in the genome, composed mostly of Tc-Mariner and hAT superfamilies that currently comprise about 9.5% of the genome.

The researchers used prior Quantitative Trait Loci (QTL) analyses of surface and cavefish crosses to discover genes that lie within these regions. Since cavefish have reduced, nearly absent eyes, the authors focused on the candidate genes for eye development and analyzed RNA-seq data to survey these genes. 30 genes under the QTL were implicated in congenital eye anomalies, with the QTL enriched for these genes. Eye-related QTL are qualitatively enriched for eye-related genes relative to the rest of the genomes, but the eye-related QTL are quantitatively more likely to contain genes associated with congenital eye defects.

The researchers investigated several promising eye-related candidate genes under the QTL by focusing on those with expression differences between surface and cavefish populations. These genes include cryaa, pitx3, and rx3. The authors also highlighted several phenotypes that co-localize with eye size, such as vibration attraction behavior and superficial neuromast number with the orbit on LG2. Interesting candidate genes in this region include shisa2, prox1, AIFM1, crxa, and Tbx2a.

The authors investigated genes that were putatively lost in the cavefish lineage since the divergence of cavefish and zebrafish by examining genes that were present in zebrafish and 8 other actinopterygian teleost from Ensembl. Potential lost genes include members of gene families involved in vision such as retinol dehydrogenases, crystallins, sine oculis homeoboxes, and opsins/rhodopsins. Lost genes related to the development and regulation of sleep and circadian clocks were also noted.

Wesley Warren, Ph.D., who lead the research at The Genome Institute, said, "The dramatic ecological changes associated with surface to cave dwelling force species to rapidly adapt or become extinct. Species that adapt to survive in harsh conditions, such as caves, provide us an opportunity to discover the molecular signatures of this change. In this first look at the blind cavefish genome, we provided some clues as to which genes are involved in these adaptive processes."