The evolutionary fluidity of sex differences – STIAS Public lecture by Diethard Tautz

23 August 2024

“There is an evolutionary fluidity in sex determination, resulting in a spectrum of phenotypes in individuals. This implies that a simple binary distinction into females and males does not properly reflect the biological reality of sex differences,” said Diethard Tautz of the Max-Planck Institute for Evolutionary Biology, Germany. “There are no binary sex phenotypes. The development of phenotypes is polygenic not binary. And, on this basis, one could ask why states need to register individuals based on sex, given that all individuals are equal by constitution anyway. We should give up registering as male or female. It’s part of a continuum and up to you to define yourself.”

STIAS Fellow Diethard Tautz during his public lecture on 13 August 2024

Tautz was presenting the first public lecture of the second semester of 2024.  He obtained his PhD in Tübingen in 1983. Following postdoc positions at the Department of Genetics in Cambridge and the Max-Planck Institute in Tübingen, he started his own group at the Department of Genetics in Munich in 1988 and then became Professor at the Department of Zoology in Munich. From 1998 to 2006 he held the chair for Evolutionary Genetics at the Department of Genetics in Cologne and since 2007 he has headed the Department of Evolutionary Genetics at the Max-Planck Institute for Evolutionary Biology in Plön. He is a member of the German National Academy Leopoldina and in 2020 received the Federal Cross of Merit for his achievements in the development of DNA fingerprinting.

“The great generality is that sexual reproduction occurs across all organisms on earth,” he continued. “Evolutionary biologists still struggle with the question of why sex is so universal, since it seems often to run contrary to short-term ecological optimisation.”

And it’s a generality that has been perpetuated at many key historical moments. Tautz showed a plaque on the 1972 Pioneer 10 Spaceship which aimed to be a message to aliens and clearly depicted humans as two sexes. “Conveying either a lifeform with binary phenotypes or that two different species cooperated to build a spaceship or that we do not know how to dress,” he joked. “It used typical human features including the average of an 8% difference in height between males and females. But we know that height is not binary – differential distributions overlap by 32%.”

“Sexual reproduction happens everywhere in life,’ he said. “The majority of organisms do it. The occurrence of sexual reproduction in all living forms suggests that in evolutionary terms sex should be one of the most stable pillars of life. But already Darwin pointed out that the effects of sexual selection can lead to very fast evolution and extreme phenotypes, such as the famous peacock’s tail.” Regarded as a classic riddle of sexual phenotypes, the Peacock’s tail was first introduced by Darwin in a letter in 1860 and further elucidated in his 1871 book The Descent of Man and Selection in Relation to Sex in which he introduced the term sexual selection suggesting that different selection regimes act on male and female phenotypes.

Explaining the history in further detail, Tautz referred to the Mendelian Rules formulated in 1865 by Austrian biologist Gregor Mendel who described heredity as combinations of independent entities and British polymath and originator of comparative statistical procedures, Francis Galton, who in 1889, described heredity as a statistical principle. In 1918 British mathematician, biologist, statistician and geneticist, Ronald Fisher combined the ideas of Darwin and Mendel and worked out the statistical link between Mendel and Galton framed as single-gene genetics versus polygenic inheritance. “Most genetic work has remained here till today,” explained Tautz. “But now polygenic genetics is being rediscovered to explain the heredity of phenotypes with a range of phenotypes across both sexes and continuum not binary variation.”

“As molecular evolutionists we study the genes that make the sexes different including not only the genes of the reproductive organs, but specifically also the genes that generate male-female differences in shared organs, such as the brain and heart. We then ask how individuals differ with respect to these so-called ‘sex-biased’ genes. It turns out that at this individual level, sex differences are much better described as overlapping distributions, rather than binary states. Moreover, the genes that determine the sex differences show extremely fast evolutionary turnover, indicative of a continuous evolutionary conflict.”

Sex ratios are part of evolutionary conflict. “We may assume it’s better to have daughters because one male can fertilise many females. But then the relative fitness of sons increases since each has a higher fraction of the offspring. A one-to-one ratio actually results in an evolutionary stable solution.”

Also there are consequences in sexual selection as the different evolutionary interests of males and females lead to divergent trait optima resulting in sexual dimorphism. “The same expression levels are suboptimal for both males and females so different expression levels develop and the genes adjust for sex differences – so there is a sex bias in gene expression which can be measured by counting the number of mRNA transcripts in an organ.”

He explained the use of the mouse model to trace these evolutionary patterns. Four closely related mouse species with defined evolutionary relationships are used. The species have a comparable evolutionary divergence as humans and chimps. The studies have looked at five somatic organs – brain, heart, kidney, liver and mammary glands and six sex organs – ovary, oviduct, uterus, testis, epidydimis and vas deferens.

And the results are surprising to most people. “If you ask which tissues have the largest number of sex bias between males and females – most guess the brain but it’s actually the least – the kidney, liver and mammary glands are the highest,” said Tautz.

“There are also major changes in the numbers of sex-biased genes between the species – which shows that the phenotypes are fluid,” he continued. If we measure evolutionary changes between the different mouse species in sex-biased genes we find that only 3% are conserved, 95% lose sex-bias in any of these species and 2% switch roles.” Putting this into context he explained that in general “about a half of non-sex related genes change expression in two million years, for sex-related ones it is 95% change. Only a small handful of sex-bias genes are conserved, the vast majority are not conserved”. (He noted also that this may also put into question the role of the mouse model in gender-specific health research.)

“Calculation of a cumulative sex-bias index which is the median expression of all female-based genes minus all male-based genes results in binary and non-binary patterns – both overlapping and distinct.” This allows to summarise the femaleness or maleness of a given individual in a single number. One can then use this to look for overlaps in variation between females and males.

Moving from mice to humans, Tautz described work doing the same evaluations using donated human tissue from the Genotype-Tissue Expression (GTEx) Portal. This has shown the highest numbers of female- and male-biased genes in the sex organs, mammary and subcutaneous fat tissues with the biggest differences between males and females. But, significantly, there are overlapping distributions for all organs except the sex organs.

“Humans are less sexually differentiated than mice,” said Tautz. “The duality of the sexes is about binary switches versus continuous distribution of phenotypes.”

In discussion, Tautz tackled issues of gender and sex, cultural and environmental factors as well as representativity in the human studies.

“No gene system is independent of environment,” he said. “For example, human height is 50% environment and 50% genes. All polygenic systems are a combination of environment and genes – we don’t yet fully understand the interactions of genes and environment.”

“The GTex database is mainly from the East Coast of the United States. There are no data on race, only sex and age. It’s not super representative. However, humans are one of the youngest species on earth, there have only been 10 000 generations, so we are very similar, much of our physiology is not that different.”

And asked about recent controversies in gender identity and sport, he replied: “Differences only really matter at the level of the Olympics – at extreme performance levels. For average sportspeople there is no difference. But at all levels one decision should be made to include/exclude an individual in a sex designation and then never be questioned again.”

“Our brains seem to be optimised to make classifications but, in reality, no one exactly fits the classification. Reality is not dichotomous.”

 

Michelle Galloway: Part-time media officer at STIAS
Photograph: Bjorn Groenewald SCPS Photography

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