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María Alicia González Manjarrez is Grade C Senior Researcher at the Instituto de Fisiología Celular Universidad Nacional Autónoma de México, México DF, México.
She is Secretary General of the Pan-American Association for Biochemistry and Molecular Biology (PABMB).

Can you introduce yourself and your line of research?

My name is Maria Alicia González Manjarrez, a biologist graduated from the Faculty of Sciences of the National Autonomous University of Mexico (UNAM). I carried out my Master’s and PhD studies at UNAM and Postdoctoral training at the University of La Sapienza in Rome, Italy. I am currently a Senior Researcher at the Cell Physiology Institute (Instituto de Fisiología Celular, IFC) of UNAM and am  Secretary General of the Pan-American Association for Biochemistry and Molecular Biology.

My group has identified some of the mechanisms resulting in paralogous sub-functionalization and the impact of gene diversification in the physiology of the yeast Saccharomyces cerevisiae. Our achievements have been documented in 65-70 publications. 

What have been your most important scientific contributions?

S. cerevisiae was the first eukaryote whose genome was fully sequenced, revealing the presence of duplicated gene blocks, indicating that this yeast lineage arose from whole genome duplication (WGD), which was later shown to be an allopolyploidization event. Gene duplication and selective retention followed by divergence may result in the generation of novel or specialized functions. Our group has identified some of the mechanisms determining selective paralogous gene retention and sub-functionalization and their impact on the physiology of the yeast. At high glucose concentrations and regardless of oxygen availability, S. cerevisiae ferments glucose to ethanol. This physiological phenomenon is called the Crabtree effect. Analysis of the role of WGD in the acquisition of fermentative metabolism in yeasts showed that species closer to Saccharomyces in the phylogenetic tree displayed a more pronounced Crabtree effect and could generate respiration deficient mutants, while most non-WGD species could not. Post-WGD species were able to generate sufficient energy to grow under strictly anaerobic conditions, while non-WGD species showed reduced ability to grow in the absence of oxygen. These observations support the proposition that the transition of yeasts to a fermentative lifestyle began before the WGD, in non-WGD yeasts, in a multistep process. However, for Saccharomycetae this metabolic trait was established after the WGD event.

My research group has carried out detailed analysis of particular duplicated pairs, showing some of the mechanisms underlying functional diversification, and recognizing some general rules on how particular changes in paralogous genes might have contributed to the acquisition of fermentative metabolism. In this regard, I will mention two examples of sub-functionalization pathways. 

Heteromeric isozyme formation: This plays a fundamental role in the functional diversification of the WGD pair encoding cytosolic NADP-Gdhs (GDH1 and GDH3), determining the biosynthesis of glutamate from ammonia and alpha-ketoglutarate, and mitochondrial Leu4/Leu9 (LEU4 and LEU9) alpha-isopropylmalate synthases (alpha-IPMSs), involved in the biosynthesis of the leucine intermediate alpha-isopropylmalate. Analysis of the diversification of these two orthologous pairs, showed for the first time that monomers of these two enzymes could be organized as homo- or heterodimers displaying peculiar kinetic properties. We concluded that retention and subsequent diversification of the two yeast Gdhs and alpha-IPMSs resulted in a specific regulatory system that controls the glutamate and leucine alpha -IPM biosynthetic pathways by selective feedback sensitivity of homomeric and heteromeric isoforms.

Development of opposite expression profiles: Analysis of the paralogous genes BAT1 and BAT2 encoding branched chain aminotransferases showed that these two genes display opposite expression profiles and physiological roles. We were able to demonstrate that the opposite regulatory action of peculiar transcription factors, the location of cis-acting elements in the promoters of BAT1 and BAT2, chromatin organization, and the metabolic state of the cell provide crucial pathways which have influenced the functional role of the paralogous BCATs in S. cerevisiae.

The increasing number of S. cerevisiae isolates and the availability of their entire genome sequences will promote further systematic studies of WGD genes from yeast collected from natural habitats, enhancing the study of the role of duplicated genes in processes other than fermentative metabolism.

What have been the main challenges that you have experienced throughout your academic and scientific career and how have you overcome those? 

In the course of the development of my scientific career, I can identify two main challenges. Firstly,  the need to recognize and accept my own capabilities. I believe that my generation was educated in an environment in which the “roles” a woman and a man had to play in our culture were artificially distributed between the two genders, and this resulted in a miss-conception of the number and type of roles I could play in life. The second challenge was to convince my teachers and fellow students, that women and men are capable of successfully studying whatever they choose, and should be treated equally. A common problem was that male professors would not accept that I could propose a working hypothesis from the results obtained that was better than their own, and I had a hard time proving I was right. My male colleagues at the same academic level were considered more capable and their propositions were readily accepted and considered for financial and academic support.

What are the major challenges faced by female scientists at your Institution?

Nowadays, women scientists enjoy what seem to be more equal opportunities and the number of positions for women scientists has increased in our Universities. However, there are some basic concepts that need to be reconsidered and analyzed. There is still the conception that females should be self-denying and good looking, and their intelligence or scientific creativity is not always considered as an important attribute. We are still the subject of sexual harassment in a variety of conceptions. In many cases the political opinion of women is not embraced like that of our male colleagues. Political roles are mainly carried out by men, and thus political decisions still have the patriarchal imprint. I believe that young women scientists in our Institutions are facing this challenge, and will have to modify this male bias. Of course, part of this problem is related to our general education, and there is a need to change the gender-role emphasis which has prevailed.

The Covid 19 pandemic has shown that a segment of the population does not believe in scientific evidence. In your opinion why is there this discredit of science? How to change this perception?

The COVID-19 pandemic has shown that the role of science, as part of the culture and development of our countries, is still not properly recognized and this problem should be addressed urgently. I believe that we could introduce novel teaching strategies that could reinforce the way we teach science in school to stimulate creativity, resulting in a scientific approach to education.

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Whole genome duplication impacted yeast metabolism