Gene copies were crucial to evolution of our eyesight 

genetic, immune cells, drug development, Diabetes, Antibiotic, hydrogen generation, chronic obstructive pulmonary disease, malaria, photosynthesis, kidney failure, Brain tumours, mental health, blood cancer, cancer, dementia, cancer treatment, antibiotic resistance, blood vessel leakage, quantum simulations, atrial fibrillation, batteries, goiter treatment, terahertz radiation, organic materials , Guild of European Research Intensive Universities, gene copies, social anxiety, blue light screens, ‘Our hope is that these findings will make it possible to discover a way to selectively inhibit the TGF-beta signals that stimulate tumour development without knocking out the signals that inhibit tumour development, and that this can eventually be used in the fight against cancer,’ says Eleftheria Vasilaki, postdoctoral researcher at Ludwig Institute for Cancer Research at Uppsala University and lead author of the study. TGF-beta regulates cell growth and specialisation, in particular during foetal development. In the context of tumour development, TGF-beta has a complicated role. Initially, it inhibits tumour formation because it inhibits cell division and stimulates cell death. At a late stage of tumour development, however, TGF-beta stimulates proliferation and metastasis of tumour cells and thereby accelerates tumour formation. TGF-beta’s signalling mechanisms and role in tumour development have been studied at the Ludwig Institute for Cancer Research at Uppsala University for the past 30 years. Recent discoveries at the Institute, now published in the current study in Science Signaling, explain part of the mechanism by which TGF-beta switches from suppressing to enhancing tumour development. Uppsala researchers, in collaboration with a Japanese research team, discovered that TGF-beta along with the oncoprotein Ras, which is often activated in tumours, affects members of the p53 family. The p53 protein plays a key role in regulating tumour development and is often altered – mutated – in tumours. TGF-beta and Ras suppress the effect of mutated p53, thereby enhancing the effect of another member of the p53 family, namely delta-Np63, which in turn stimulates tumour development and metastasis.

A new study published in BMC Evolutionary Biology sheds light on the evolutionary origin of vertebrate vision and the specialisations in zebrafish to adapt to rapidly changing light conditions. The research was led by Xesús Abalo and Dan Larhammar, the Department of Neuroscience at Uppsala University and SciLifeLab,

Light perception is crucial for the survival of all major animal groups, including our own – the vertebrates. Evolution has favoured selection of the camera eye that arose in the vertebrate ancestor more than 500 million years ago. Light perception takes place in the cone and rod cells of the retina through a set of proteins. The light information registered by these cells is partially processed in the retina and then forwarded to the brain for further processing and integration with other sensory systems, eventually leading to outputs such as regulation of behaviours.

Twenty years ago, the first studies of the light receptor proteins in birds indicated that colour vision, mediated by cones, arose before the dim light greyscale vision provided by rods. This hypothesis was recently confirmed by the team led by Abalo and Larhammar in a detailed study on the visual opsin gene family, analysing a broad range of vertebrate species (Lagman and Ocampo Daza et al., 2013).

In the current study, the same group presents a detailed analysis on the evolution of the PDE6 proteins, the main effectors of light sensitivity in cones and rods. They show that the genes encoding PDE6 arose from ancestral genes that duplicated in the early vertebrate genome doublings, and further expanded in teleosts due to the extra genome duplication that took place in this lineage. They also identified another ancient vertebrate gene copy that has been lost in amniotes.

To functionally characterize the PDE6 family members, they studied zebrafish and analysed the specific specialisations in its visual system – since zebrafish have three extra gene duplicates that arose after it diverged from the lineage leading to humans. Zebrafish display the same distinction as humans between cone and rod versions of PDE6. In addition to this, the gene duplicates in zebrafish display strikingly different activity during the day–night cycle, presumably to allow efficient regulation of photoreceptor cells under different light conditions.

Altogether, the study reinforces the evolutionary importance of the two rounds of whole genome duplication that occurred in the vertebrate ancestor and sheds light on the different behaviour of gene duplicates that arose in these events. The large difference in day and night activity for the gene duplicates opens doors to functional studies of behaviours regulated by light in different animal groups.

Reference: Evolution and expression of the phosphodiesterase 6 genes unveils vertebrate novelty to control photosensitivity