Researchers uncovered that genes turned on in some cancers in humans also exist in zebrafish — but are ‘silenced’ within just hours of fertilisation. The study sheds new light on how our epigenetics can regulate genes, some of which are linked to cancer development later in life, over large evolutionary distances. It also uncovers significant differences between how the epigenome ‘resets itself’ in zebrafish and human embryos, which may guide future studies on epigenetic inheritance. …
Humans and zebrafish are estimated to have shared a common ancestor 400 million years ago. How do the zebrafish do things?
The team uncovered fundamental differences in how DNA is methylated in mammalian and zebrafish embryos.
In humans, these DNA methylation tags are mostly ‘swept clean’ when a sperm fertilises an egg, and then gradually methylated again, to ensure the embryo can develop correctly. Instead, zebrafish embryos retain the methyl group pattern of the father.
In this study, the researchers found that primordial germ cells of zebrafish do not reset their methylation patterns either, but inherit paternal DNA methylation patterns. This contrasts with findings in mammalian primordial germ cells, which undergo a second ‘sweep cleaning’ of their DNA methylation tags. The researchers say this finding sheds light on the molecular principles of germline development and highlights zebrafish as a useful experimental model to study how epigenetic signatures are inherited throughout generations.
Further, the researchers screened how DNA is methylated in zebrafish embryos, at four stages of development. They discovered 68 genes that were methylated and turned off early during embryonic development, within 24 hours of fertilisation.
“What was interesting is that most of these genes belong to a group called cancer testis antigens,” says Dr Ksenia Skvortsova, co-first author of the study. “Our work shows that these are some of the very first genes that are ‘silenced’, or targeted by DNA methylation, in both zebrafish and mammals.”
The genes that code for cancer testis antigens, or CTAs for short, are only active in the male testis, but are turned off in all other tissues, in humans. For an unknown reason, CTA genes are turned on again in some cancers, such as melanomas.
“Mammals and fish have very different strategies when it comes to developing an embryo,” says Dr Bogdanovic. “But in spite of these very different strategies, it appears that the control of CTA genes are conserved throughout evolution.” Paper. (open access) – Ksenia Skvortsova, Katsiaryna Tarbashevich, Martin Stehling, Ryan Lister, Manuel Irimia, Erez Raz, Ozren Bogdanovic. Retention of paternal DNA methylome in the developing zebrafish germline. Nature Communications, 2019; 10 (1) DOI: 10.1038/s41467-019-10895-6 More.
The main thing we’re learning these days is that epigenetics is much more important than we used to think. Which means that purely Darwinian evolution must be much less so.
See also: What if there is no genetics apart from epigenetics
Epigenetic learning confirmed in nematodes; Weismann barrier broken
Epigenetic change: Lamarck, wake up, you’re wanted in the conference room!