Sex determination and SRY: down to a wink and a nudge?

Team Comprehension Worksheet

The goal for this worksheet is to make sure that each one of you has the background knowledge regarding sex determination in humans that will be required to perform your ethics activity for today. As you read Sex determination andSRY: down to a wink and a nudge? use the questions in this worksheet as a guide, don’t be afraid to ask questions for clarification, and keep the following summary statement from the paper in mind each time you find yourself getting bogged down in the details:

“Overall, sex determination is a story of opposing forces and crucial alliances but, although the winning team takes all, its rule can be surprisingly tenuous.”

What specifies sex? The quest for the Holy Grail.

1)What does SRY stand for?

2)The paper refers to a ‘conserved 79 amino acid domain within SRY’. What does this mean?

3)What is the conserved domain similar to?

4)What do these types of domains tend to do to DNA?

5)May different genes have been discovered that play a role in sex determination. What are the three broad categories in which their involvement can be classified?

Sry and its protein product

6)What is known about the timing of SRY expression, and what does this mean about its role in testes differentiation?

Sry transcriptional regulation

7)If a protein activates a promoter, what impact does that have on the transcription of the gene associated with the promoter? What ultimate impact would that have on overall protein production?

8)What are some candidates for genes whose products might activate SRY promoters?

Sox9: an SRY-target gene (in mice, at least…)

9)What is a loss of function (LOF) mutant?

10)What is a gain of function (GOF) mutant?

11)What sex are Sox9 LOF mutants who are XY?

12)What sex are Sox9 GOF mutants who are XX?

13)According to the authors, Sox9 expression has 3 phases: initiation, upregulation and maintenance. Which of these phases is Sry-dependent?

14)What is TESCO and how does in impact transcription of Sox9?

15)What do the authors think the role of SF1 and SRY are in the initiation and upregulation Sox9 expression?

How is Sox9 expression maintained?

16)What is an autoregulatory feedback loop?

17)What mechanism does Sox9 appear to use to help maintain its own expression?

What happens downstream of SOX9?

18) What impact(s) is SOX9 suspected to have on the following cell types?

  1. Follicle cells
  1. Sertoli cells

The balance between testicular and ovarian genes

19) The authors state that, “ovarian development is established by active repression of one or more genes in the testicular pathway rather than it depending entirely on a passive ‘default’ pathway.” What role (s) does b-catenin seem to play in this view of sex differentiation?

20)What role (s) does FOXL2 seem to play in the regulation of sex differentiation?

Sex Determination without Sry: are there common themes in evolution?

21) Is the notion that the Y chromosome always determines maleness and the female condition is the ‘default’ supported by evolutionary evidence? Give one genetic and one non-genetic example to support your answer.

Summary:

22)Now you should be able to summarize Figure 3in your own words.