Edinburgh Research Explorer

The evolutionary genomics of X chromosomes

Project: Research

  • Charlesworth, Brian (Principal Investigator)
  • Betancourt, Andrea J. (Researcher)
  • Marion de Proce, Sophie (Researcher)
Effective start/end date5/12/084/03/12
Total award£422,134.00
Funding organisationBBSRC
Funder project referenceBB/G003076/1


This is an investigation of the evolutionary processes affecting the X chromosome, using a combination of whole-genome sequencing and analyses of molecular variation within species.

Layman's description

The sex of an individual is often determined by a pair of special chromosomes (the carriers of genetic information), X and Y. In many animal species, females carry two copies of the X, and males carry an X and a Y. Both males and females carry two copies of each of the other chromosomes, one derived from the mother and the other from the father. The X is a typical chromosome but the Y has only a small number of functional genes (the portions of the DNA that specify the structures of proteins). This means that most new mutations that occur on the X and alter gene function will affect males, since there is no normal copy to cover up their effects. In contrast, a mutation on the X in a female will be present together with a normal copy, just like a mutation on another chromosome. Natural selection is thus better at removing harmful mutations if they arise on the X, since part of the time they are carried in males and express their effects fully. Similarly, useful mutations that increase the fitness of their carriers may have a better chance of causing evolutionary change if they arise on the X. These differences can have important consequences, such as more evolutionary change involving mutations that improve fitness (positive selection) on the X than chromosomes not concerned with sex determination; this is the ‘Faster-X’ hypothesis.
The ability to determine the sequences of the four ‘letters’ in DNA that make up the genetic information means that we can directly measure rates of evolutionary change by comparing DNA sequences between species. Such comparisons have been used to ask whether rates of evolution differ between genes on the X chromosome, and those elsewhere in the genome. The results concerning the Faster-X hypothesis have so far been conflicting. We have used an unusually favourable system for comparisons of this kind, to help to resolve these conflicts. This involved a group of species of the fruitfly Drosophila (the pseudoobscura group), where a regular chromosome has effectively been turned into an additional X chromosome. This allowed us to compare rates of evolution of genes on this chromosome with rates for the same genes on the equivalent chromosome in other Drosophila species, where it behaves normally. We obtained the sequences of over 4000 genes from a species in this group, Drosophila affinis, and selected a set of over 100 fast-evolving genes from among these. We collected data on variation on these genes within another species, Drosophila pseudoobscura. This allows the use of statistical tests for positive selection, as opposed to the chance accumulation of mutations with little effect on fitness. The results of our studies provide no support for the Faster-X effect; indeed they showed that, for the new X chromosome, positive selection is not the cause of the rapid evolution of the genes we studied. Another strong conclusion was that fast evolving genes whose products are produced in females, but not in males, show a high rate of positive selection, in contrast to the prevailing view that genes expressed in males but not females should show this pattern.
We also studied a different process, the addition and deletion of small pieces of DNA. This process is important for the evolution of genome size, but is poorly understood. We used publicly available data on between-species differences and within species variability to examine the nature of the evolutionary forces acting on additions and deletions. The results show that insertions that increase the length of sequences within genes that have no obvious functional significance are favoured by selection when the sequences are shorter than average, but deletions are favoured when the sequences are longer than average. The X was not unusual in this respect.
This research integrates evolutionary genetic and computational approaches to maximize the understanding gained from genome sequences, and provides new tools and insights concerning evolutionary mechanisms.

Key findings

1. An Illumina sequence of the genome of Drosophila affinis has been generated in collaboration with the Schloetterer group in Vienna, providing an additional species with which to study the D. pseudoobscura group, an important model system for evolutionary
2. Using these sequences, together with our data on variation within D. pseudoobscura,we compared protein sequence evolution in the D. pseudoobscura group with the D. melanogaster group, with the specific aim of testing for the ‘Faster-X’ effect. No evidence for this was detected, but we found more adaptive evolution of genes expressed
primarily in females.
3. We also used publicly available information on between- and within-species variation in insertions and deletions of DNA in introns to infer the nature of selection on such length changes. There was support for stabilizing selection on the length of introns, i.e. insertions are favoured in short introns, and deletions in long introns.


Research outputs