RESUMEN
This research examines how the human genome and SES jointly and interactively shape verbal ability among youth in the U.S. The youth are aged 12-18 when the study starts. The research draws on findings from the latest GWAS as well as a rich set of longitudinal SES measures at individual, family and neighborhood levels from Add Health (N = 7194). Both SES and genome measures predict verbal ability well separately and jointly. More interestingly, the inclusion of both sets of predictors in the same model corrects for about 20% upward bias in the effect of the education PGS, and implies that about 20-30% of the effects of parental SES are not environmental, but parentally genomic. The three incremental R2s that measure the relative contributions of the two PGSs, the genomic component in parental SES, and the environmental component in parental SES are estimated to be about 1.5%, 1.5%, and 7.8%, respectively. The total environmental R2 and the total genomic R2 are, thus, 7.8% and 3%, respectively. These findings confirm the importance of SES environment and also pose challenges to traditional social-science research. Not only does an individual's genome have an important direct influence on verbal ability, parental genomes also influence verbal ability through parental SES. The decades-long blueprint of including SES in a model and interpreting their effects as those of SES needs to be amended accordingly. A straightforward solution is to routinely collect DNA data for large social-science studies granted that the primary purpose is to understand social and environmental influences.
RESUMEN
The T-cell protein tyrosine phosphatase (TCPTP/PTPN2) targets a broad variety of substrates across different subcellular compartments. In spite of that, the structural basis for the regulation of TCPTP's activity remains elusive. Here, we investigated whether the activity of TCPTP is regulated by a potential allosteric site in a comparable manner to its most similar PTP family member (PTP1B/PTPN1). We determined two crystal structures of TCPTP at 1.7 and 1.9 Å resolutions that include helix α7 at the TCPTP C-terminus. Helix α7 has been functionally characterized in PTP1B and was identified as its allosteric switch. However, its function is unknown in TCPTP. Here, we demonstrate that truncation or deletion of helix α7 reduced the catalytic efficiency of TCPTP by â¼4-fold. Collectively, our data supports an allosteric role of helix α7 in regulation of TCPTP's activity, similar to its function in PTP1B, and highlights that the coordination of helix α7 with the core catalytic domain is essential for the efficient catalytic function of TCPTP.
Asunto(s)
Proteína Tirosina Fosfatasa no Receptora Tipo 2/química , Proteína Tirosina Fosfatasa no Receptora Tipo 2/metabolismo , Regulación Alostérica , Sitio Alostérico/genética , Secuencia de Aminoácidos , Sustitución de Aminoácidos , Fenómenos Biofísicos , Dominio Catalítico/genética , Cristalografía por Rayos X , Humanos , Cinética , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Conformación Proteica en Hélice alfa , Proteína Tirosina Fosfatasa no Receptora Tipo 1/química , Proteína Tirosina Fosfatasa no Receptora Tipo 1/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 1/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 2/genética , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transducción de SeñalRESUMEN
Recently, several genome-wide association studies of educational attainment have found education-related genetic variants and enabled the integration of human inheritance into social research. This study incorporates the newest education polygenic score (Lee et al., 2018) into sociological research, and tests three gene-environment interaction hypotheses on status attainment. Using the Health and Retirement Study (N = 7599), I report three findings. First, a standard deviation increase in the education polygenic score is associated with a 58% increase in the likelihood of advancing to the next level of education, while a standard deviation increase in parental education results in a 53% increase. Second, supporting the Saunders hypothesis, the genetic effect becomes 11% smaller when parental education is one standard deviation higher, indicating that highly educated parents are more able to preserve their family's elite status in the next generation. Finally, the genetic effect is slightly greater for the younger cohort (1942-59) than the older cohort (1920-41). The findings strengthen the existing literature on the social influences in helping children achieve their innate talents.
