Z chromosome linked DMRT1 determines sex in Birds

By | April 27, 2021
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Andrew Sinclair’s group in Murdoch children research institute in Australia deciphered the mechanism involved in avian sex determination, which has been a long-standing mystery in the field of developmental biology. Prof Sinclair’s group focuses on sex determination, and aims to understand how genes control gonad development. Development of the gonads (testes or ovaries) requires the coordinated functioning of many genes and proteins.

Sex determination in Birds like mammals is chromosomally depended but sex chromosomes as well as mechanism is largely different. All males in Birds possess have two Z chromosomes while females have one Z and one W chromosome. In the case of mammals: males have one X and one Y chromosome and females have two copies of X chromosomes. The Y chromosome of males carry the male-dominant testis-determining gene SRY. However there is no indication of a Bird SRY genes nor there is no clear idea of a candidate gene responsible for female determination on W chromosome ,which provides a rather fuzzy picture of mechanism involved in sex determination of birds.

Research published in last month issue of Nature led by Craig Smith provides conclusive evidence for Z linked DMRT1 as Bird sex-determination gene. DMRT1, encodes a protein containing a cysteine-rich DM domain that, at least in invertebrates, transcriptionally regulates target genes, has long been suspected as a candidate for bird sex determination. This gene is specifically transcribed in testis and is not dosage compensated (both copes on Z chromosome remains active) , while females contains only one copy of DMRT1.This provided a clue that DMRT1 could function in a dose related manner , where a certain threshold of protein of DMRT1 is required to make testis in males.These amounts can be reached only in Males as they contains two Z chromosomes, while females could reach only half of this amount. This insufficiency leads the ZW gonad in females to pursue a default female pathway.

Andrew Sinclairs group performed RNA interference (RNAi) to knock down DMRT1 in early chicken embryos. The result of reducing the amounts of DMRT1 in male embryos was remarkable, the gonads developed into ovaries rather than testes. These data strongly support the hypothesis that DMRT1 is the chicken sex-determining gene and provide direct evidence that it functions by dosage differences between males and females. The level of DMTR1 is critical and particular threshold is required for the activation of male developmental pathway and this is possible only in the case of male birds with two Z chromosomes.

These knock down embryos for DMRT1 also shows reduced expression of a male marker gene SOX9, but levels of a female marker gene aromatase (which is generally not present in male embryos) increased.

These above results predict masculinize genetically female (ZW) embryos in the converse experiment when DMRT1 is over expressed. However the authors don’t have a system yet to over express DMTR1 only in gonads cells ,while over expression in entire embryos lead to lethality of embryos at day 4 before gonadal sex differentiation.

This discovery also helped us to understand determination of sex in vertebrates a little better. DMTR1 gene is present and involved in sex determination in different vertebrates and invertebrates, suggesting in has an ancient role.Additionally the observation that monotreme mammals (the egg-laying platypus and the echidna, which diverged from all other mammals 166 million years ago at the base of the mammalian evolutionary tree) share genes similar to ZW system of birds , including DMRT1 gene unlike mammalian XY system. Observations like these indicate that ZW system of birds was ancestral to all amniotes (birds,reptiles and mammals) and SRY gene is comparatively new to sex determination arena. This work by smith et al., fills in a huge gap in our understanding of the evolution of vertebrate sex chromosomes


The avian Z-linked gene DMRT1 is required for male sex determination in the chicken.
Smith CA, Roeszler KN, Ohnesorg T, Cummins DM, Farlie PG, Doran TJ, Sinclair AH.
Nature. 2009 Sep 10;461(7261):267-71.