Systematic Identification And Database Construction Of Sex-associated Genes In 21 Species With Multiple Tissues And Multiple Developmental Stages

Sexual dimorphism is prevalent among sexually reproduction species in nature,there are huge differences in many phenotypic characteristics and behaviors between females and males.Previous research reported that sex differences in genome level might be limited to sex-specific chromosomes.Most sexual dimorphism is caused by the expression of female biased or male biased in Sex-Associated Gene(SAG)shared by both sexes.Almost all human complex traits and disease phenotypes show a certain degree of sex dimorphism.However,the SAG that causes most of the phenotypic sex differences is still unknown.Current research on sex-bias is often limited to a single species or project.How to prove that the sex-bias influence obtained through disease model research of model organisms can also be used in human diseases is an important challenge facing sex-biased research.This project is dedicated to establishing a standardized process and platform for systematic identification of SAG,so that it is possible to compare gene expression between sexes across species.This study manually collated the common RNA-seq datasets with paired male and female organisms under the same conditions,and systematically re analyzed these datasets using standardized methods.A total of 2,828 samples from 21 species were systematically identified 27793 female biased SAGs and 64043 male biased SAGs.Including human,chimpanzee,macaque,mouse,rat,cattle,horse,chicken,zebrafish,seven kinds of fly and five kinds of worm species.All these data were classified into the user-friendly database of SAGs——Sex-Associated Gene Database(SAGD,http://bioinfo.life.hust.edu.cn/SAGD),where users can browse SAGs based on gene,species,drug and data set information.In SAGD,SAG expression,annotation,targeted drugs,homologs,ontology and related RNA-seq datasets are provided to help researchers explore its functions and potential applications in agriculture and human health.Based on these SAGs that have been recognized by the system and included in SAGD,this research has carried out the characteristic analysis of SAG from three directions: 1).The study selected five species from SAGD that contain multiple tissues and have different sex chromosome systems for analysis.These five species include human,rat,mouse,Drosophila melanogaster and chicken.2).Found that SAG showed different levels of sexbiased distribution in different tissues.All tissues of chicken are enriched with more femalebiased SAG.The SAG in various tissues of other species showed more male biased.We infer that the biased distribution of SAG may be related to the sex chromosome system.3).Based on the association information between SAG and sex chromosomes in the data collected by SAGD,we were able to study the enrichment bias of SAG on sex chromosomes in different species.Genes with sex-biased expression are distributed in small or excessive amounts on the X chromosome.Different species have different patterns.The distribution biased of SAG on the sex chromosomes of chickens with the only female heterogamous(ZW/ZZ)sex chromosome system is also different from other species of male heterogamous(XX/XY)sex chromosome system.This article speculates that different sex chromosome systems and even different species may have different strategies to face the pressure of sexual selection.Different sex chromosome systems are subject to different selection pressures.Based on the mammal data collected by SAGD,this article also explores the conservation of SAG within and between species.The analysis shows that SAG is relatively conservative within species but less conservative between species,which may indicate that genetic sex-biased is closely related to species.Researchers need to be cautious about using animal models to study sex differences in diseases.This research will contribute to explore the scientific research of sex differences.In today's era of big data,the work results of scholars from all over the world who are dedicated to studying sex differences are gathered and shared.We hope that these collated and included data will not only provide a solid data foundation for theoretical research on sex evolution,but also can contribute to the research on sex differences in diseases and promote the development of precision medicine.