Sex differences in expression of X and Y genes during development of the human and chimpanzee central nervous system
(English)Manuscript (preprint) (Other academic)
Global microarray gene expression analyses have demonstrated that female and male embryos differ in terms of gene expression during neurodevelopment. In particular, before sexual maturation of the gonads, the differences concentrate on the expression of genes encoded on the X and Y chromosomes. Precision measurements of expression levels of X and Y gametolog genes have been hampered by the high sequence identity between each pair of X and Y homologs. To address this issue, as well as to interrogate genome-wide for differences in expression during early human development, we combined high resolution RNA sequencing technology with a nested qPCR strategy to analyse CNS samples from 8-11 weeks old human embryos. We found that, besides genes known to bind oestrogen and androgen receptors, the largest biased group consisted of genes encoded on the Y chromosome. This list of Y chromosome genes included fifteen previously known MSY genes, thirteen of which have known gametologs encoded on the X chromosome. In addition, we found 6 novel non-annotated long non-coding RNAs, four of which are poly-adenylated and show conserved expression patterns in the brain of a chimpanzee male new born. Among X-encoded genes, we found that besides XIST, only seven genes had significantly higher expression in female embryos. Of these, only three, including ZFX, KDM5C, and NLGN4X have known gametologs encoded on the Y chromosome.
In summary, the contribution of Y chromosome gene expression during early CNS development is larger than previously anticipated, while the amount of X-encoded gametolog genes that presented female-bias was limited. These results clearly indicate that the time is ripe to conduct functional studies directed to understand the male specific function of Y genes during early CNS development.
y chromosome, male, female, fetal, embryo, human, spinal cord, medulla oblongata, expression, sex biased, sex differences, conserved, chimpanzee, chimp, brain, XY, X chromosome, KDM5C, KDM5D, UTX, UTY, PCDH11Y, PCDH11X; NLGN4Y, NLGN4X, non-coding RNA, ncRNA, lincRNA, RNAseq, RNA sequencing, polyA, qPCR, Jazin, Johansson, könsskillnader
Neurosciences Developmental Biology
Research subject Biology with specialization in Molecular Biology; Neurology
IdentifiersURN: urn:nbn:se:uu:diva-261685OAI: oai:DiVA.org:uu-261685DiVA: diva2:851232
FunderSwedish Research Council, K2012-61X-22089-01-3