Sex determination via conserved molecular mechanisms

Structure–function analysis of mouse Sry reveals dual essential roles of the C-terminal polyglutamine tract in sex determination

Excerpt: “We demonstrate, using a combination of biochemical, cell-based, and transgenic mouse assays, that this domain plays essential roles in both protein stabilization and transactivation of Sox9, and is required for male sex determination in mice. Our data indicate that mouse Sry has evolved a novel bifunctional module, revealing an unexpected level of plasticity of sex-determining mechanisms even among mammals.”

2) Plasticity in the transcriptional and epigenetic circuits regulating dendritic cell lineage specification and function (2014)

Excerpt: “Rapid developments in single cell genomics are beginning to provide us with robust tools to potentially revise the working models of DC specification and the common hematopoietic tree.”

3) From Fertilization to Adult Sexual Behavior (1996)

“Yet another kind of epigenetic imprinting occurs in species as diverse as yeast, Drosophila, mice, and humans and is based upon small DNA-binding proteins called “chromo domain” proteins, e.g., polycomb. These proteins affect chromatin structure, often in telomeric regions, and thereby affect transcription and silencing of various genes (Saunders, Chue, Goebl, Craig, Clark, Powers, Eissenberg, Elgin, Rothfield, and Earnshaw, 1993Singh, Miller, Pearce, Kothary, Burton, Paro, James, and Gaunt, 1991Trofatter, Long, Murrell, Stotler, Gusella, and Buckler, 1995). Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species, Drosophila melanogaster and Caenorhabditis elegans (Adler and Hajduk, 1994de Bono, Zarkower, and Hodgkin, 1995Ge, Zuo, and Manley, 1991Green, 1991Parkhurst and Meneely, 1994Wilkins, 1995Wolfner, 1988). That similar proteins perform functions in humans suggests the possibility that some human sex differences may arise from alternative splicings of otherwise identical genes.”

My comment:  In 1996, co-author TB linked molecular epigenetics (in our review, with co-author Milton Diamond) to cell type differentiation in the sexes. Others have since linked the common hemataopoietic tree to the differentiation of cell types in all cells of all tissues in all organs of all organ systems of all mammals via the same molecular mechanisms. The conserved molecular mechanisms of cell type differentiation in species from microbes (e.g., yeasts) to man indicate that sex differences in cell types are nutrient-dependent pheromone-controlled ecological adaptations. 

No experimental evidence of biologically-based cause and effect suggests that typical or atypical differences in cell types arise via mutation-initiated natural selection and the evolution of biodiversity. Thus, it appears that biophysical constraints on the stability of protein folding, which is required to organize the increasingly complex genomes of extant organisms, also prevents mutation-driven evolution of the sexes.

This does not indicate that men and women come from different planets, or that any other differences in morphological or behavioral phenotypes are caused by mutation-driven evolution. It indicates that nutrient-dependent alternative splicing techniques of pre-mRNA link the stability of DNA in the organized genome of all mammals — via the circulatory system — from changes in the microRNA/messenger RNA balance to amino acid substitutions that stabilize DNA.

That suggests how the epigenetic landscape becomes the physical landscape of DNA, which enables biodiversity via the metabolism of nutrients to species-specific pheromones. Pheromones control the physiology of reproduction, which is dependent on the ability of the common hemataopoietic tree in mammals to link epigenetic effects on hormones to their transgenerational affects on mammalian behavior via the circulatory system. 

Summary: The epigenetic landscape becomes the physical landscape of DNA via the metabolism of nutrients to species-specific pheromones that control the physiology of reproduction. Controlled nutrient-dependent reproduction enables biodiversity manifested in morphological and behavioral phenotypes. Epigenetic effects on hormones are linked to their transgenerational affects on mammalian behavior via stem cells that become circulating cells, which deliver important messages that typically enable ecological adaptations to occur in the absence of mutations. 

See for contrastReduced selection and accumulation of deleterious mutations in genes exclusively expressed in men. “We conclude that deleterious mutations in male testis-exclusive genes tend to accumulate in the human population in spite of the morbid phenotypes they are likely to cause, specifically in male reproduction processes. The more than twofold higher occurrence of such mutations in male-specific genes, relative to the other gene groups we tested in this work, is remarkable since these mutations potentially inhibit the propagation of their genotype by causing infertility. Our findings suggest that testis-exclusive genes as leading candidates in the genetic aetiology of male infertility. In general, our results emphasize the importance of mapping the sex-specific genetic architecture of humans in order to better understand the evolutionary constraints acting on these genes.


About James V. Kohl 1308 Articles
James Vaughn Kohl was the first to accurately conceptualize human pheromones, and began presenting his findings to the scientific community in 1992. He continues to present to, and publish for, diverse scientific and lay audiences, while constantly monitoring the scientific presses for new information that is relevant to the development of his initial and ongoing conceptualization of human pheromones. Recently, Kohl integrated scientific evidence that pinpoints the evolved neurophysiological mechanism that links olfactory/pheromonal input to genes in hormone-secreting cells of tissue in a specific area of the brain that is primarily involved in the sensory integration of olfactory and visual input, and in the development of human sexual preferences. His award-winning 2007 article/book chapter on multisensory integration: The Mind’s Eyes: Human pheromones, neuroscience, and male sexual preferences followed an award winning 2001 publication: Human pheromones: integrating neuroendocrinology and ethology, which was coauthored by disinguished researchers from Vienna. Rarely do researchers win awards in multiple disciplines, but Kohl’s 2001 award was for neuroscience, and his 2007 “Reiss Theory” award was for social science. Kohl has worked as a medical laboratory scientist since 1974, and he has devoted more than twenty-five years to researching the relationship between the sense of smell and the development of human sexual preferences. Unlike many researchers who work with non-human subjects, medical laboratory scientists use the latest technology from many scientific disciplines to perform a variety of specialized diagnostic medical testing on people. James V. Kohl is certified with: * American Society for Clinical Pathology * American Medical Technologists James V. Kohl is a member of: * Society for Neuroscience * Society for Behavioral Neuroendocrinology * Association for Chemoreception Sciences * Society for the Scientific Study of Sexuality * International Society for Human Ethology * American Society for Clinical Laboratory Science * Mensa, the international high IQ society