Function Over Form:
Phenotypic Integration and the Evolution of the Mammalian Skull

By Claire Asher, on 8 December 2014

Our bodies are more than just a collection of independent parts – they are complex, integrated systems that rely upon precise coordination in order to function properly. In order for a leg to function as a leg, the bones, muscles, ligaments, nerves and blood vessels must all work together as an integrated whole. This concept, known as phenotypic integration, is a pervasive characteristic of living organisms, and recent research in GEE suggests that it may have a profound influence on the direction and magnitude of evolutionary change.

Phenotypic integration explains how multiple traits, encoded by hundreds of different genes, can evolve and develop together such that the functional unit (a leg, an eye, the circulatory system) fulfils its desired role. Phenotypic integration could be complete – every trait is interrelated and could show correlated evolution. However, theoretical and empirical data suggest that it is more commonly modular, with strong phenotypic integration within functional modules. This modularity represents a compromise between a total lack of trait coordination (which would allow evolution to breakdown functional phenotypic units) and the evolutionary inflexibility of complete integration. Understanding phenotypic integration and its consequences is therefore important if we are to understand how complex phenotypes respond to natural selection.

Functional modules in mammals, Goswami et al (2014)

Functional modules in mammals, Goswami et al (2014)

It is thought that phenotypic integration is likely to constrain evolution and render certain phenotypes impossible if their evolution would require even temporary disintegration of a functional module. However, integration may also facilitate evolution by coordinating the responses of traits within a functional unit. Recent research by GEE academic Dr Anjali Goswami and colleagues sought to understand the evolutionary implications of phenotypic integration in mammals.

Expanding on existing mathematical models, and applying these to data from 1635 skulls from nearly 100 different mammal species including placental mammals, marsupials and monotremes, Dr Goswami investigated the effect of phenotypic integration on evolvability and respondability to natural selection. Comparing between a model with two functional modules in the mammalian skull and a model with six, the authors found greater support for a larger number of functional modules. Monotremes, whose skulls may be subject to different selection pressures due to their unusual life history, did not fit this pattern and may have undergone changes in cranial modularity during the early evolution of mammals. Compared with random simulations, real mammal skulls tend to be either more or less disparate from each other, suggesting that phenotypic integration may both constrain and facilitate evolution under different circumstances. The authors report a strong influence of phenotypic integration on both the magnitude and trajectory of evolutionary responses to selection, although they found no evidence that it influences the speed of evolution.

Thus, phenotypic integration between functional modules appears to have a profound impact on the direction and extent of evolutionary change, and may tend to favour convergent evolution of modules that perform the same function (e.g bird and bat wings for powered flight), by forcing individuals down certain evolutionary trajectories. The influence of phenotypic integration on the speed, direction and magnitude of evolution has important implications for the study of evolution, particularly when analysing fossil remains, since it can make estimates of the timing of evolutionary events more difficult. Failing to incorporate functional modules into models of evolution will likely reduce their accuracy and could produce erroneous results.

Phenotypic integration is what holds together functional units within an organism as a whole, in the face of natural selection. Modularity enables traits to evolve independently when their functions are not strongly interdependent, and prevents evolution from disintegrating functional units. Through these actions, phenotypic integration can constrain or direct evolution in ways that might not be predicted based on analyses of traits individually. This can have important impacts upon the speed, magnitude and direction of evolution, and may tend to favour convergence.

Original Article:

() Global Environmental Change


This research was made possible by support from the Natural Environment Research Council (NERC), and the National Science Foundation (NSF).

Size Matters: Why Reduced Sexual Ornaments are Rarely Seen

By Claire Asher, on 29 October 2013

Across the animal kingdom, males have evolved fancy physical ornaments, songs and courtship rituals, all in an attempt to attract the opposite sex. Most of the male ornaments and sexually-selected traits biologists tend to study are large, elaborate and flamboyant. But mathematical models predict that sexual selection is just as likely to make an ornament smaller or more modest as it is to make it more elaborate. Recent research by Dr Sam Tazzyman and Prof Andrew Pomiankowski from UCL’s Department of Genetics, Evolution and Environment, in collaboration with Prof Yoh Iwasa at Kyushu University, investigates why male ornaments tend to get bigger rather than smaller.

Male and Female Red Deer
Image by Deepsky, Creative Commons Licence

Sexual selection is the process whereby traits are favoured because they increase an individual’s success at obtaining mates, often at the expense of survival or condition. Sexual selection is a special case of natural selection, where natural selection is concerned with increasing the overall fitness of an organism. Sexual selection may act in opposition to natural selection, when traits that make you more attractive to the opposite sex also make you less fit in other ways. In these cases, the form a trait takes may be somewhere between the most attractive (sexual selection optimum) and the most fit (natural selection optimum). Sexual selection has been the focus of a great deal of evolutionary research, both experimental and theoretical, because it has the power to generate extreme physical and behavioural adaptations: huge antlers, complicated courtship displays, brightly coloured plumage, etc. Most research has focussed on bright, bold, exaggerated traits like these. But theory suggests that sexual selection should be just as likely to drive traits to be less extreme (than the natural selection optimum) as it is to make them more extreme. So why don’t we see sexually reduced traits much in nature?

First, Tazzyman and collegues searched the literature on mate choice and sexual selection for examples of reduced sexual traits – that is, cases in which females prefer males with a trait smaller, duller or less elaborate than the natural selection optimum. They found that for many types of trait, reduction simply isn’t possible, or is extremely difficult to define. For example, when a sexually-selected trait is a particular colour of a patch of plumage, how can we define exaggeration or reduction in this trait? Is the size of the patch most relevant, or the hue or saturation of colour? Similarly, for many traits, the natural selection optimum might be zero – no trait at all. For example, in many species the male is brightly coloured while the female is dull, here the dull colouration can be considered no trait and is assumed to be the natural selection optimum. Likewise, in many species the males carry physical adornments such as the red crests (or combs) of many gamefowl, which are totally absent in females.

Male and Female Junglefowl

Certainly, these issues with definition occur most frequently for colour, pheromone and behavioural traits. Morphological traits tend to lend themselves more readily to being classified on a simple scale, in which both exaggeration and reduction of that trait is possible. There are a few cases of females showing a preference for a smaller trait, but these examples are few and far between. Of 40 sexual traits for which both elaboration and reduction could be defined, 34 were found to be subject to sexual selection for exaggeration.

This imbalance may be partly explained by our own observation bias – smaller traits may be more difficult to detect and so tend not to become the subject of study. But, it is unlikely this is the full explanation. However, it seems that females may suffer a similar problem; if biologists aren’t noticing small ornaments, maybe the females aren’t either. This is one of three possible hypotheses that Tazzyman and colleagues tested to explain the apparent asymmetry in the direction of sexual selection. Male ornaments are signals, aimed at attracting a female – if that trait cannot easily be seen or detected by the female, then it cannot serve it’s purpose. Consistent with this, a mathematical model of sexual selection assuming asymmetrical signalling efficacy (where smaller traits are less effective at conveying their message) showed that exaggerated traits were more likely to undergo the ‘runaway’ selection characteristic of sexually-selected ornaments.

Peacock and Peahen
Image by ToastyKen, CC Licence

Their models also ruled out two other possible explanations – that it is more costly for a female to prefer a small trait than a large one, and that is it more costly for a male to carry a small trait than a large one. Neither of these models resulted in a bias towards exaggeration. Only models including an asymmetry in the efficacy of signalling produced results that mirror what we observe in nature.

Sexual selection acts upon traits that make one sex more attractive to the other, and can favour characteristics that are otherwise detrimental to survival or condition. Sexual selection has the power to generate the bright, flamboyant, exaggerated characteristics such as antlers that we see in many animals. Although many theoretical models predict both exaggeration and reduction in sexual traits, in wild populations, we rarely see this – almost all documented sexual traits are more extreme than their natural selection optimum. Sexual traits act as signals to the opposite sex, and this may explain why in the wild, sexual selection tends to exaggerate and elaborate traits which are more visible to females and so more effective at communicating their message.

Original Article:

() Evolution

This research was made possible by funding from the Natural Environment Research Council (NERC), and the Engineering and Physical Sciences Research Council (EPSRC)

Maintaining the Status Quo:
Constraints on the Evolution of Gene Regulation

By Claire Asher, on 10 September 2013

Every living cell, whether solitary or part of a larger multicellular organism, is an extremely complex system, involving a multitude of simultaneous chemical reactions regulated by proteins and RNA. Keeping this machine running relies upon a careful balance of gene expression and protein degradation, and cells must be prepared to modulate these processes in response to environmental variation (both internal and external). Homeostatic mechanisms can be an efficient way to regulate gene expression, however one key mechanism – negative autoregulation – is rarely used in organisms like flies and humans. Mathematical modelling by GEE’s Max Reuter and Andrew Pomiankowski shows that evolutionary constraints in the evolution of negative feedback may exist for species who carry multiple copies of each chromosome in their cells.

A Eukaryotic (Animal) Cell and a Prokaryotic (Bacterial) Cell

Homeostasis: From Radiators to Cells
One of the simplest ways to regulate any system is through negative feedback, whereby a particular process is inhibited by the products of that process. This is the system employed by central-heating systems, which use the temperature to regulate the action of a radiator. The radiator pumps out heat, and when the thermometer detects too much heat in the room, it signals the radiator to stop. Negative feedback systems can be highly efficient, stable and responsive.

Negative feedback, or homeostasis, would also be a sensible way to regulate the expression of genes within a cell – a particular gene would continue to be expressed and produce its protein product until there is enough of that product in the cell, at which point expression would stop. This system would be sensitive to the demands of the cell – if the product was being used up quickly, then expression would continue as long as demand was high. In fact, many simple, single-celled organisms, such as E. coli, use this system to respond quickly to changes in their environment.

Around half of all genes in Escherichia coli are regulated by this kind of negative feedback loop, known as negative autoregulation. However, when we look at other organisms such as yeast (Saccharoymyces cerevisiae), fruit flies (Drosophila melanogaster), and humans, we find a very different picture – almost no genes show signs of negative autoregulation (around 2%). If negative autoregulation is such a neat solution to apparently common problem, why aren’t humans and flies using it?

By Ehamberg (Own work)
[CC-BY-SA-3.0 or GFDL],
via Wikimedia Commons

A Matter of Ploidy
One of the key differences between humans and E. coli (although probably not the one that springs to mind!), is that E. coli carry only a single copy of each gene in each cell. They are haploid, with a single circular chromosome in each cell that carries a single copy of each gene in the E. coli genome. By contrast, humans, yeast and fruit flies are all diploid, meaning that they carry two copies of each gene in every cell. Our genes are split up into many, straight chromosomes, and we have two copies of each chromosome. Recent research in the department of GEE has used a mathematical modelling approach to investigate how diploidy (having two sets of chromosomes) might constrain the evolution of negative autoregulation.

In a paper in PLoS Computational Biology in March this year, Dr Alexander Stewart, Professor Rob Seymour, Professor Andrew Pomiankowski and Dr Max Reuter from UCL’s GEE produced a mathematical model of how gene regulation might evolve differently in species with one or two sets of chromosomes. Their model focuses on mutations in the promoters of genes, which alter how other protein molecules interact with and repress the expression of those genes.

In haploids, with a single copy of each gene, negative autoregulation produces very tight regulation of gene expression, giving a very rapid response to changing demand. Likewise, in a diploid species with two identical copies of a particular gene, negative autoregulation tends to be beneficial and achieves very efficient gene regulation.

Constraints in the Evolution of Regulation
The problem arises when the diploid carries two different variants of the same gene. This would be the situation whenever a new mutation arises – new mutations appear in a single copy of a particular gene. For a new mutation to be favoured and spread through the population, it must be able to do well, at least initially, as a single copy. The mutated gene must be able to work well alongside the original version. And this is where the problem arises. Stewart, Seymour, Pomiankowski and Reuter (2013) found that mutations that altered the negative autoregulation of a gene didn’t tend to play well with others. Their model considered mutations that alter the strength of the binding site – essentially how strongly regulated that gene is. An individual carrying one strongly regulated gene and one weakly regulated gene actually did worse than an individual with two weakly regulated genes. These heterozygote individuals responded more slowly to changes in demand, and there was more noise in the system. This situation, known as underdominance, where a genetic variant has a lower fitness in the heterozygote form, could be a major constraint to evolution.


Underdominance in negatively autoregulated systems arises because of the disparity in binding site strength between the two different copies of a gene. As each gene pumps out gene product, the stronger binding site is quickly suppressed by the product produced by both genes. It takes much longer for the weaker binding site to be suppressed, as it requires more product to be activated, and most of this is being used up by the stronger binding site. Compared to a haploid, the strong site shows faster response times but the weak site shows a much slower response time, and this averages out to an overall slower response.

Stewart et al (2013)’s model showed that the extent of underdominance depended on how different the two genetic variants were. Large differences in the strength of their binding sites reduced response time and created more noise than smaller differences. Slower response times and increased noise in heterozygotes mean that the maximum strength of regulation achievable in a diploid may be as much as ten-fold lower than in haploids.

Because very small differences between genetic variants in their binding site strength did not experience such a strong effect of underdominance, they were more likely to lead to the evolution of autoregulation. Evolution in diploids could proceed through many very small changes, however there is also likely to be lower limit on the size of mutations – very small changes cannot be ‘seen’ by natural selection and are unlikely to spread. Likewise, multiple binding sites, each relatively weak but which act together cooperatively, were also more likely to overcome the issue of underdominance in the model. However, in general, diploids had a much harder time evolving negative feedback as a mechanism for gene regulation. This evolutionary constraint might have forced diploids such as fruit flies and humans to develop alternative mechanisms to achieve rapid responses, such as increased rates of protein degradation or alternative regulatory mechanisms.

Original Article:

() PLOS Biology

This research was made possible by funding from the Natural Environment Research Council (NERC), the Engineering and Physical Sciences Research Council (EPSRC), and the McDonnell Foundation