Question

In chickens, a key gene involved in sex determination has recently been identified. Called \(D M R T 1\), it is located on the \(Z\) chromosome and is absent on the W chromosome. Like SRY in humans, it is male determining. Unlike \(S R Y\) in humans, however, female chickens (ZW) have a single copy while males (ZZ) have two copies of the gene. Nevertheless, it is transcribed only in the developing testis. Working in the laboratory of Andrew sinclair (a co-discoverer of the human SRY gene), Craig Smith and colleagues were able to "knock down" expression of \(D M R T 1\) in \(\mathrm{ZZ}\) embryos using RNA interference techniques (see Chapter 15 ). In such cases, the developing gonads look more like ovaries than testes [Nature 461: 267 (2009)]. What conclusions can you draw about the role that the DMRTI gene plays in chickens in contrast to the role the SRY gene plays in humans?

Short answer

Question: Describe the role of the DMRT1 gene in chickens and explain how it differs from the SRY gene in humans, based on the experiment conducted by Craig Smith and colleagues. Answer: The DMRT1 gene in chickens plays a crucial role in determining maleness and testis development, similarly to the SRY gene in humans. However, the DMRT1 gene determines maleness based on the presence of Z chromosomes, while the SRY gene is linked to the Y chromosome in humans. The experiment conducted by Craig Smith and colleagues showed that reducing the expression of DMRT1 in male chicken embryos led to the development of gonads resembling ovaries, highlighting the importance of DMRT1 in testis development and emphasizing the differences between DMRT1 and SRY in sex determination.

Step-by-step solution

Understand the genes DMRT1 and SRY

We will start by understanding the role of the DMRT1 gene in chickens and the SRY gene in humans. Both genes are involved in sex determination. DMRT1 is located on the Z chromosome in chickens and is absent on the W chromosome. In chickens, the gene is male-determining. Female chickens (ZW) have a single copy of the gene, while male chickens (ZZ) have two copies. The gene is transcribed only in the developing testis. Therefore, DMRT1 plays a role in determining maleness in chickens. SRY is a similar gene in humans, and it is also male determining. However, there are differences in their structure and function that we should take into account when comparing their roles in sex determination.

Examine the experiment conducted

In the experiment conducted by Craig Smith and colleagues, they were able to "knock down" the expression of DMRT1 in ZZ embryos using RNA interference techniques. This means that they reduced the activity of the DMRT1 gene in the developing male chicken embryos. As a result, the developing gonads in these embryos appeared to look more like ovaries than testes. This finding suggests that the DMRT1 gene plays a crucial role in the development of testes in male chickens.

Compare the roles of DMRT1 and SRY

Now that we understand the role of the DMRT1 gene in chickens, we can compare it to the role of the SRY gene in humans. Both genes are involved in sex determination and are male-determining. However, there are some differences between them. For example, the presence of DMRT1 on either one or two Z chromosomes determines maleness, while its absence on the W chromosome determines femaleness in chickens. In contrast, humans have an XY sex-determination system, where the presence of the SRY gene on the Y chromosome determines maleness. Furthermore, DMRT1 is only transcribed in the developing testis of male chickens, while the SRY gene has a broader function in humans. The experiment by Smith and colleagues showed that reducing the expression of DMRT1 in ZZ embryos leads to the development of gonads resembling ovaries, indicating the importance of DMRT1 in testis development.

Draw conclusions

In conclusion, the DMRT1 gene in chickens plays a crucial role in determining maleness and testis development, similarly to the SRY gene in humans. However, there are differences between the two genes - DMRT1 determines maleness based on the presence of Z chromosomes, while the SRY gene is linked to the Y chromosome in humans. The experiment conducted by Craig Smith and colleagues highlights the importance of DMRT1 in testis development and further emphasizes the differences between the DMRT1 and SRY genes in sex determination.

Key concepts

Understanding the DMRT1 Gene

The DMRT1 gene plays a pivotal role in chicken sex determination, mirroring the function of the SRY gene in humans, albeit with notable differences. In chickens, DMRT1 is a critical factor in the process that leads to the development of male characteristics and is found on the Z chromosome, which is part of their unique ZW sex chromosome system. Females possess one copy of this gene (as ZW), while males have two (ZZ), underscoring a gene dosage effect—where the quantity of gene product influences the phenotypic outcome.

Interestingly, the transcription of DMRT1 is specific to the developing testis, which indicates that its expression is tightly regulated and associated with male-specific developmental pathways. The concept of gene dosage and regulated expression becomes particularly pertinent when considering the results of experiments that utilize RNA interference (RNAi), where the repression of DMRT1 expression in embryos led to the development of gonadal structures more akin to ovaries than testes. This suggests that DMRT1 is indispensable for testis formation and the promotion of male sexual differentiation in chickens.

In humans, while the SRY gene holds a similar sex-determining role, it is present on the Y chromosome and does not manifest a dosage effect. Each of these genes—DMRT1 and SRY—highlight the diversity in sex determination mechanisms that have evolved across species.

The Role of the SRY Gene

SRY, short for Sex-determining Region Y, is a gene that dictates male sex determination in humans. Located on the Y chromosome, it acts as a switch that initiates testis development and subsequent male sexual differentiation. When the SRY gene is active, it triggers a cascade of genetic events leading to the formation of testes, which then produce hormones responsible for the development of male physical characteristics.

The presence of the SRY gene implies that in humans, sex determination is binary and primarily dependent on the presence (XY for males) or absence (XX for females) of this singular gene. This differs from the chicken DMRT1 gene, where the number of copies is linked to sex determination, indicating the variability of genetic strategies employed across organisms in establishing male phenotypes.

A key aspect to highlight is that in humans, mutations in the SRY gene can lead to disorders of sex development (DSD). These conditions exemplify the critical role that SRY plays in the intricate process of human sexual differentiation, making it a focal point in the study of human genetics and reproductive biology.

Chicken Sex Chromosomes and Sex Determination

Chickens employ a ZW sex chromosome system, which contrasts with the human XY system, to determine sex. In this system, the female chickens have distinct Z and W chromosomes (ZW), while males possess two Z chromosomes (ZZ). The DMRT1 gene's presence on the Z chromosome is pivotal since its dosage, whether as a single copy in females or double in males, influences the developmental route of the gonads.

Understanding this system has profound implications for avian genetics and sex determination. It also sheds light on how sex chromosomes can evolve different mechanisms for such a fundamental biological process. Notably, the sensitivity of the gonadal development pathway in chickens to the quantity of DMRT1 implicates this gene as a key regulatory element in the sex determination hierarchy. This system elucidates the sex determination process's adaptability and complexity across different species, highlighting evolution's role in diversifying genetic methods of development.

RNA Interference in Gene Expression Regulation

RNA interference (RNAi) is a powerful biological process used by cells to regulate gene expression and defend against viruses. It involves small RNA molecules that can target specific messenger RNA (mRNA) molecules for degradation, thereby preventing the translation of those mRNAs into proteins. This mechanism can be harnessed in a laboratory setting to silence the expression of specific genes, as seen in the experiment conducted by Smith and colleagues.

By using RNAi to 'knock down' the expression of DMRT1 in chicken embryos, researchers could observe the effects on gonadal development, which underscores both RNAi's utility as a research tool and the critical role of DMRT1 in sex determination. This technique holds promise not only for uncovering gene functions but also has therapeutic potential for treating diseases by silencing harmful genes.

Testis Development in Sexual Differentiation

Testis development is a complex, gene-driven process that is crucial for male sexual differentiation and reproductive capability. In chickens, the DMRT1 gene is transcribed specifically within the developing testes, indicating its central role in testis formation. This process is orchestrated by a symphony of genetic interactions and hormonal influences, which if disrupted—as seen through RNAi targeting of DMRT1—can result in the manifestation of ovary-like structures in genetic males (ZZ).

Human testis development begins with the activation of SRY and involves a similar but distinct set of genes that propagate the male developmental path. Understanding the genetics behind testis development in various species not only informs us about the intricacies of sexual differentiation but also helps in diagnosing and managing sex development disorders. The study of these genes and their pathways remains a dynamic field of research with implications for medicine, agriculture, and evolutionary biology.