1. G ENE DUPLICATIONS : PSEUDOGENES Alba Vilella Figuerola Genomics MSc in Advanced Genetics Universitat Autònoma de Barcelona

2. OVERVIEW What are pseudogenes? How do they arise? Pseudogenes and evolution Do they have a function? PTEN and PTENP1 Regulation of nNOS

3. Pseudogene : copy of a gene that has lost the capacity to produce a functional protein. (Pink et al, 2013) First discovered in X. laevis in 1977 by Jacq et. al Presents in plants, bacteria, insects, nematode worms and mammals. Nowadays we know that, in humans, are almost as numerous as coding genes (10,000 – 20,000).

4. H OW DO THEY ARISE ? Pink, R. C. et al (2013)

5. Most of them are copies of housekeeping genes. Gerstein M, Zheng D. (2006)

6. P SEUDOGENES AND E VOLUTION They are sometimes considered to represent neutral sequence  can accumulate mutations that are not selected But: Do not have as many STOP codons as they should have if being under neutral selection. Some have conserved sequences (ORFs, coding sequence...) 50% conserved with Rhesus monkey 3% conserved with mice Then.... DO THEY HAVE A FUNCTION ?

7. M OST OF THEM ARE TRANSCRIBED Their RNA (lnc-RNA) can be detected by RNA-seq Microarrays RT-PCR Can have tissue-specific transcription. Can have a different expression pattern from parental genes.

8. S O... W HAT IS THEIR F UNCTION ? Poliseno, L. et al (2015)

9. Pink, R. C. et al (2013)

10. EVIDENCES: PTEN AND PTENP1 In normal conditions: PTENPTENP1 RNAm Degradation miRNA

11. EVIDENCES: PTEN AND PTENP1 In cancer: PTENPTENP1 RNAm Degradation For example in colon cancer.

12. EVIDENCE: R EGULATION OF N NOS Lymnaea stagnalis Korneev, S. et al (1999)

13. CONCLUSIONS Pseudogenes are sequences that normally do not produce protein and that, in some cases, can be transcribed. Pseudogenes are conserved. They have functional roles as lnc-RNA: gene regulation increasing variability and new gene production production of proteins analogous to the ones coded in the parental genes They are implicated in some diseases.

14. R EFERENCES Gerstein M, Zheng D; (2006). The real life of pseudogenes. Sci. Am. 295(2): 48– 55 Groen, J. N., Capraro, D., Morris, K. V. (2014). The emerging role of pseudogene expressed non-coding RNAs in cellular functions. International Journal of Biochemistry and Cell Biology, 54, 350–355. doi:10.1016/j.biocel.2014.05.008 Korneev, S. a, Park, J. H., O’Shea, M. (1999). Neuronal expression of neural nitric oxide synthase (nNOS) protein is suppressed by an antisense RNA transcribed from an NOS pseudogene. The Journal of Neuroscience : The Official Journal of the Society for Neuroscience, 19(18), 7711–7720. Milligan, M. J., & Lipovich, L. (2014). Pseudogene-derived lncRNAs: emerging regulators of gene expression. Frontiers in Genetics, 5(February), 476. doi:10.3389/fgene.2014.00476 Pink, R. C., Carter, D. R. F. (2013). Pseudogenes as regulators of biological function. Essays in Biochemistry, 54, 103–12. doi:10.1042/bse0540103 Pink, R. C., Wicks, K., Caley, D. P., Punch, E. K., Jacobs, L., Raul, D., Carter, F. (2011). Pseudogenes: Pseudo-functional or key regulators in health and disease? RNA, 17, 792–798. doi:10.1261/rna.2658311.transcription Poliseno, L., Marranci, A., Pandolfi, P. P. (2015). Pseudogenes in Human Cancer. Frontiers in Medicine, 2(September), 1–8. doi:10.3389/fmed.2015.00068