Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes

Evolutionary changes in the anatomy and physiology of the female reproductive system underlie the origins and diversification of pregnancy in Eutherian ('Placental') mammals. This developmental and evolutionary history constrains normal physiological functions and biases the ways in which dysfunction contributes to reproductive trait diseases and adverse pregnancy outcomes. Here, we show that gene expression changes in the human endometrium during pregnancy are associated with the evolution of human-specific traits and pathologies of pregnancy. We found that hundreds of genes gained or lost endometrial expression in the human lineage. Among these are genes that may contribute to human-specific maternal-fetal communication (HTR2B) and maternal-fetal immunotolerance (PDCD1LG2) systems, as well as vascular remodeling and deep placental invasion (CORIN). These data suggest that explicit evolutionary studies of anatomical systems complement traditional methods for characterizing the genetic architecture of disease. We also anticipate our results will advance the emerging synthesis of evolution and medicine ('evolutionary medicine') and be a starting point for more sophisticated studies of the maternal-fetal interface. Furthermore, the gene expression changes we identified may contribute to the development of diagnostics and interventions for adverse pregnancy outcomes.

Evolutionary transcriptomics implicates new genes and pathways in human pregnancy and adverse pregnancy outcomes

Evolutionary changes in the anatomy and physiology of the female reproductive system underlie the origins and diversification of pregnancy in Eutherian (“Placental”) mammals. This developmental and evolutionary history constrains normal physiological functions and biases the ways in which dysfunction contributes to reproductive trait diseases and adverse pregnancy outcomes. Here, we show that gene expression changes in the human endometrium during pregnancy are associated with the evolution of human-specific traits and pathologies of pregnancy. We found that hundreds of genes gained or lost endometrial expression in the human lineage. Among these are genes that may contribute to human-specific maternal-fetal communication (HTR2B) and maternal-fetal immunotolerance (PDCD1LG2) systems, as well as vascular remodeling and deep placental invasion (CORIN). These data suggest that explicit evolutionary studies of anatomical systems complement traditional methods for characterizing the genetic architecture of disease. We also anticipate our results will advance the emerging synthesis of evolution and medicine (“evolutionary medicine”) and be a starting point for more sophisticated studies of the maternal-fetal interface. Furthermore, the gene expression changes we identified may contribute to the development of diagnostics and interventions for adverse pregnancy outcomes.

Diet-related Physiological Plasticity of Mourning Doves: A Metabolomic Approach (P09-002-19)

Objectives As birds are a natural model of diabetes, the objective of this study was to test the hypothesis that feeding adult mourning doves, Zenaida macroura, a high fat diet (60% calories from fat; HF) or refined carbohydrate diet (white bread: WB) for four weeks results in diabetes-like pathologies including hyperglycemia and altered metabolic profiles. Methods Separate cohorts of doves were captured for each feeding trial and were acclimated for one week to their respective study diets; cohort 1: WB (n = 6) vs nutritionally-balanced seeds (n = 6), and cohort 2: HF (n = 4) vs control (n = 6). The WB study mimicked natural feeding options for wild birds whereas the HF study used experimental diets. Four weeks later, birds were euthanized with an overdose of sodium pentobarbital and we collected cardiac blood, liver, kidney (HF study only), and pectoralis muscle for metabolomic analyses and biochemical assays. Results Pathway analysis of metabolic concentrations revealed only two pathways that were significantly altered (p < 0.05) and concurrently highly impacted (scale: 0-1; > 0.60) by the HF diet consumption: ubiquinone and other terpenoid-quinone biosynthesis (plasma and pectoralis muscle) and alanine, aspartate, and glutamate metabolism (plasma and kidney; p < 0.05). Only three low impact pathways were significantly affected by the WB diet consumption: glutathione metabolism and histidine metabolism (liver), and glyoxylate and dicarboxylate metabolism (pectoralis muscle; p < 0.05). Further, consumption neither of the HF nor of the WB diet altered plasma uric acid, insulin, pectoralis muscle, liver triglycerides, or body mass (only measured in HF study) significantly, but liver glycogen concentrations were 2.12-fold higher in WB than control doves (p < 0.015). Lastly, blood glucose concentrations did not differ between WB or HF birds and control birds. Conclusions Contrary to our hypothesis, consumption of a WB or HF diet for four weeks did not induce symptoms of diabetes in doves. Further elucidating the apparent avian resistance to diet-induced metabolic complications may help develop novel therapeutic agents for mammalian diabetes. Funding Sources ASU School of Life Sciences/Office of Knowledge Enterprise Development - Research Investment Initiative, a summer research fellowship from the American Physiology Society, and the Center of Evolution and Medicine Graduate Fellow Award.

Core Principles for Evolutionary Medicine

New interest in evolution and medicine arose late in the twentieth century from the recognition that there are several possible kinds of evolutionary explanation for aspects of the body that leave it vulnerable to disease, in addition to the inevitability of mutations. Investigations of related hypotheses have led to rapid growth of evolutionary medicine, and its expansion to integrate demographic, phylogenetic, and population genetic methods. Evolutionary approaches to understanding disease are part of a major transition in biology, from viewing the body as a designed machine to a fully biological view of the body’s organic complexity as fundamentally different from that of designed machines.

A Manifesto for a Processual Philosophy of Biology

This chapter argues that scientific and philosophical progress in our understanding of the living world requires that we abandon a metaphysics of things in favour of one centred on processes. We identify three main empirical motivations for adopting a process ontology in biology: metabolic turnover, life cycles, and ecological interdependence. We show how taking a processual stance in the philosophy of biology enables us to ground existing critiques of essentialism, reductionism, and mechanicism, all of which have traditionally been associated with substance ontology. We illustrate the consequences of embracing an ontology of processes in biology by considering some of its implications for physiology, genetics, evolution, and medicine. And we attempt to locate the subsequent chapters of the book in relation to the position we defend.

Accessing and applying molecular history

Studying the evolutionary history of life’s molecules - DNA, RNA, and protein - reveals nature-based solutions to real-world problems. We discuss an approach to applied molecular evolution that is well-known within the field but may be unfamiliar to a wider audience. Using a case study at the intersection of molecular evolution and medicine, we introduce the fundamental concepts of orthology and paralogy. We also explain a practical entry point to molecular evolution named STORI: Selectable Taxon Ortholog Retrieval Iteratively. STORI is a machine learning algorithm designed to clear a bottleneck that researchers encounter when studying evolution.

Accessing and applying molecular history

Studying the evolutionary history of life’s molecules - DNA, RNA, and protein - reveals nature-based solutions to real-world problems. We discuss an approach to applied molecular evolution that is well-known within the field but may be unfamiliar to a wider audience. Using a case study at the intersection of molecular evolution and medicine, we introduce the fundamental concepts of orthology and paralogy. We also explain a practical entry point to molecular evolution named STORI: Selectable Taxon Ortholog Retrieval Iteratively. STORI is a machine learning algorithm designed to clear a bottleneck that researchers encounter when studying evolution.

Differential Evolution Approach to Detect Recent Admixture

The genetic structure of human populations is extraordinarily complex and of fundamental importance to studies of anthropology, evolution, and medicine. As increasingly many individuals are of mixed origin, there is an unmet need for tools that can infer multiple origins. Misclassification of such individuals can lead to incorrect and costly misinterpretations of genomic data, primarily in disease studies and drug trials. We present an advanced tool to infer ancestry that can identify the biogeographic origins of highly mixed individuals. reAdmix can incorporate individual's knowledge of ancestors (e.g. having some ancestors from Turkey or a Scottish grandmother). reAdmix is an online tool available at http://chcb.saban-chla.usc.edu/reAdmix/.