Human genetics just got a whole lot more complicated with a report published last week by Isidore Rigoutsos’ team in Oncotarget. As if differences in expression profiles between cells, tissues and differentiation stages weren’t already enough, it seems that race and gender also affect genomic output.
Specifically, the team focused on transfer RNAs (tRNAs). tRNAs may seem like unassuming molecules to some, with a dull factory-floor job in the production line of proteins. However, they can give rise to shorter tRNA fragments (tRFs) through cleavage, and while it is still unclear what these molecules actually do, they have been shown to affect many physiological processes, including cell growth and response to DNA damage.
They have been found in all corners of life, from bacteria and archaea to yeast and mammals, but they have not yet been extensively catalogued in humans.
To study the diversity of tRFs in human populations, Rigoutsos’ team focused on RNA-seq datasets from two large samples: lymphoblastoid cell lines derived from 452 healthy men and women representing five different races, and 311 samples of primary breast cancer tissue.
After some pretty impressive number crunching and displays of technical prowess required to cope with these repetitive sequences, here’s what they found:
- They discovered a new type of tRF which they called ‘internal tRNA fragments’ (i-tRFs) because i-tRFs begin and end in the interior of a mature tRNA.
- Mitochondrial tRNAs are a rich source of tRFs.
- Characteristics of tRFs such as their abundance and length depended on disease status, race, population and gender; for example, levels of 93 tRFs differed significantly between white and black populations.
These findings tie in with a previous study by the same team showing that miRNA isoforms also depend on gender, population and race. Rigoutsos sums up the implications of this work. “We now have to take into account race-dependencies and gender-dependencies when studying the molecular biology of disease. Will what we learn from a cell line from someone in North Europe still apply to someone from South Europe?”
“Yes there is complexity but knowledge of that complexity means more power for researchers going forward”.
Check out just how complicated things can get at Oncotarget, July 2015.