The Nß motif of NaTrxh directs secretion as an endoplasmic reticulum transit peptide and variations might result in different cellular targeting.

Soluble secretory proteins with a signal peptide reach the extracellular space through the endoplasmic reticulum-Golgi conventional pathway. During translation, the signal peptide is recognised by the signal recognition particle and results in a co-translational translocation to the endoplasmic reticulum to continue the secretory pathway. However, soluble secretory proteins lacking a signal peptide are also abundant, and several unconventional (endoplasmic reticulum/Golgi independent) pathways have been proposed and some demonstrated. This work describes new features of the secretion signal called Nß, originally identified in NaTrxh, a plant extracellular thioredoxin, that does not possess an orthodox signal peptide. We provide evidence that other proteins, including thioredoxins type h, with similar sequences are also signal peptide-lacking secretory proteins. To be a secretion signal, positions 5, 8 and 9 must contain neutral residues in plant proteins-a negative residue in position 8 is suggested in animal proteins-to maintain the Nß motif negatively charged and a hydrophilic profile. Moreover, our results suggest that the NaTrxh translocation to the endoplasmic reticulum occurs as a post-translational event. Finally, the Nß motif sequence at the N- or C-terminus could be a feature that may help to predict protein localisation, mainly in plant and animal proteins.

Aplanar y exhibir la variación: dos estrategias de investigación de la genética humana en México / Flattening and Unpacking Variation: Two Research Strategies of Human Genetics in Mexico / Aplanar e exibir a variação: duas estratégias de pesquisa da genética humana no México

Resumen Introducción: este artículo analiza dos estrategias de investigación puestas en acción en tres proyectos de estudio de la genética humana en México, entre 1960 y 2009. Se distingue entre una estrategia que incorpora recursos multidisciplinarios en el diseño del muestreo, el análisis e interpretación de datos (a la que se le denomina de exhibición), y una que privilegia consideraciones pragmáticas sobre los análisis multidisciplinarios (a la que se le denomina de aplanamiento). Desarrollo: se analizó el trabajo del médico hematólogo Rubén Lisker en la década de 1960, el mapeo de la diversidad genómica mexicana realizado por investigadores del Instituto Nacional de Medicina Genómica entre 2004 y 2009, y el análisis de la variación nativa llevado a cabo por el genetista Andrés Moreno (en la Universidad de Stanford en ese entonces), y sus colegas en años recientes. Conclusiones: las decisiones estratégicas que toman los científicos tienen consecuencias en la medición y caracterización de la variación genética en las poblaciones humanas, pero también sobre las prácticas sociales demográficas y biomédicas relacionadas con su estudio. Mientras la primera estrategia exhibe de forma detallada la variación genética oculta en las poblaciones humanas, favoreciendo así la precisión y el realismo, la segunda tiende a aplanar las diferencias individuales y a perder profundidad histórica, pero privilegiando la generalización y la descripción de los grandes rasgos de una población.

Abstract Introduction: This article analyzes two research strategies carried out by three projects of human genetics in Mexico, between 1960 and 2009. We distinguish between a strategy that incorporates multidiscipli-nary resources in the design of sampling, analysis and interpretation of data (which we call exhibition), and one that privileges pragmatic considerations on multidisciplinary analysis (which we call flattening). Development: We analyzed the work of the hematologist Rubén Lisker in the 1960s, the mapping of Mexican genomic diversity carried out by researchers from the National Institute of Genomic Medicine between 2004 and 2009, and the analysis of the native variation carried out by geneticist Andrés Moreno (then at Stanford University), and his colleagues in recent years. Conclusions: The strategic decisions taken by scientists have consequences in the measurement and characterization of genetic variation in human populations, but also in the demographic and biomedical social practices related to their study. While the first strategy exhibits detailed genetic variation hidden in human populations, thus favoring precision and realism, the second tends to flatten individual differences and lose historical depth, but privileging the generalization and description of the broad features of a population.

Resumo Introdução: este artigo analisa duas estratégias de pesquisa colocada em prática em três projetos de estudo da genética humana no México, entre 1960 e 2009. Distinguimos entre uma estratégia que incorpora recursos multidisciplinares no desenho da amostragem, a análise e interpretação de dados (à qual chamamos de exibição), e uma que privilegia considerações pragmáticas sobre as análises multidisciplinares (a qual chamamos de aplanamento). Desenvolvimento: analisamos o trabalho do médico hematólogo Rubén Lisker na década de 1960, o mapeamento da diversidade genômica mexicana realizado por pesquisadores do Instituto Nacional de Medicina Genômica (INMEGEN) entre 2004 e 2009, e a análise da variação nativa levado a cabo pelo geneticista Andrés Moreno (para então na Universidade de Stanford), e seus colegas em anos recentes. Conclusões: as decisões estratégicas que tomam os científicos têm consequências na medição e caracterização da variação genética nas populações humanas, mas também sobre as práticas sociais demográficas e biomédicas relacionadas com o seu estudo. Enquanto a primeira estratégia exibe de forma detalhada a variação genética oculta nas populações humanas, favorecendo assim a precisão e o realismo, a segunda tende a aplanar as diferenças individuais e a perder profundidade histórica, mas privilegiando a generalização e a descrição dos grandes rasgos de uma população.

Flattening and Unpacking Human Genetic Variation in Mexico, Postwar to Present.

Argument This paper analyzes the research strategies of three different cases in the study of human genetics in Mexico - the work of Rubén Lisker in the 1960s, INMEGEN's mapping of Mexican genomic diversity between 2004 and 2009, and the analysis of Native American variation by Andrés Moreno and his colleagues in contemporary research. We make a distinction between an approach that incorporates multiple disciplinary resources into sampling design and interpretation (unpacking), from one that privileges pragmatic considerations over more robust multidisciplinary analysis (flattening). These choices have consequences for social, demographic, and biomedical practices, and also for accounts of genetic variation in human populations. While the former strategy unpacks fine-grained genetic variation - favoring precision and realism, the latter tends to flatten individual differences and historical depth in lieu of generalization.