Why is a Dolphin Not a Cat?

How repurposing non-coding elements in the genome gave rise to the great 'mammalian radiation'

Friday, 30 January 2015

Exploring gene regulation in 20 mammals

provides insights into the mammalian radiation

that occurred over 100 million years ago. Credit:

Spencer Phillips, EMBL-EBI.

New research shows how evolution has given rise to a rich diversity of species by repurposing functional elements shared by all mammals. Published in Cell by scientists at the European Bioinformatics Institute (EMBL-EBI) and the University of Cambridge Cancer Research UK-Cambridge Institute (CRUK CI), the study demonstrates how methods for understanding human biology can be used to understand a broad range of species.

Mammals all share a common ancestor, and they share a lot of the same genes. So what exactly makes a dolphin not a cat, and how did we all start to diverge from one another millions of years ago? Part of the answer lies in how - and when - genes are regulated. This latest research explores the evolution of gene regulation in 20 mammalian species, and provides deep insights into the 'mammalian radiation', a time of rapid morphological evolution that occurred shortly after the asteroid impact that caused the extinction of the dinosaurs.

Leveraging findings from a study comparing the genome sequences of 29 mammals, and with the help of conservation organisations such as the UK Cetacean Strandings Investigation Programme and the Copenhagen Zoo, the team were able to study and compare gene regulation in liver cells from 20 key species including the naked mole rat, human, Tasmanian devil, dolphin and Sei whale.

"What we've shown is that evolution repurposes things that exist in all species, to make each species unique," explains Paul Flicek, head of Vertebrate Genomics at EMBL-EBI.

"By looking at gene promoters and enhancers in many different mammals, we demonstrated that species-specific enhancers come from ancient DNA - that evolution captures DNA that's been around for a long time, and uses it for gene regulation in specific tissues."

Evolution has two ways to turn changes in the genome into differences between species: it can change a protein sequence, or it can change the way promoters or enhancers control that protein's expression. Today's study also shows that in some cases evolution uses both strategies at once. When amino acid sequences evolve very quickly, important regulation changes occur at the same time: the protein-coding sequence and the corresponding regulatory sequence change synergistically.

Gathering the samples - the experimental efforts were led by Diego Villar of CRUK CI - took well over two years, and the experiments themselves produced a staggering volume of data. Analysing the results brought the team to a new frontier in bioinformatics.

"People spend a lot of time and money trying to understand human biology, so most of the tools we have are designed to study human genomes," explains Camille Berthelot of EMBL-EBI, who led the computational work.

"The reference data we have for the less studied species, like the Sei whale or Tasmanian devil, are nothing like the pored-over datasets we have for the human genome. A lot of what we did involved benchmarking, and making sure the methods and algorithms were fit for this kind of comparison."

"What inspired this work was a desire to get on top of the mountain, look out and see what is going on in the landscape of molecular evolution across the breadth of mammalian space," says Duncan Odom of CRUK CI and Wellcome Trust Sanger Institute.

"What's exciting about this study is that we now know we can start to answer questions about the functional genetics of many under-explored species - questions we usually can ask only of humans and mice. We can use tools developed to study humans to understand the biology of all kinds of animals, whether they're blackbirds or elephants, and explore their relationship with one another. This research has given us new insights into mammalian evolution, and proven how powerful these methods can be."

Source: EMBL

Contact: Mary Todd Bergman

Reference:

Enhancer Evolution across 20 Mammalian Species

Diego Villar, Camille Berthelot, Sarah Aldridge, Tim F. Rayner, Margus Lukk, Miguel Pignatelli, Thomas J. Park, Robert Deaville, Jonathan T. Erichsen, Anna J. Jasinska, James M.A. Turner, Mads F. Bertelsen, Elizabeth P. Murchison, Paul Flicek, Duncan T. Odom

Cell, Volume 160, Issue 3, p554–566, 29 January 2015, DOI: http://dx.doi.org/10.1016/j.cell.2015.01.006

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ZenMaster

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Father's Age Influences Rate of Evolution

Chimpanzee.

Father's Age Influences Rate of Evolution

Friday, 13 June 2014

The offspring of chimpanzees inherit 90% of new mutations from their father, and just 10% from their mother, a finding which demonstrates how mutation differs between humans and our closest living relatives, and emphasises the importance of father's age on evolution.

Published today in Science, researchers from the Wellcome Trust Centre for Human Genetics and the Biomedical Primate research Centre in the Netherlands looked at whether, in chimpanzees, there was a heightened risk of fathers passing on mutations to their children compared to humans.

In humans, each individual inherits, on average, about 70 new mutations from their parents. However, this number is influenced by paternal age such that older fathers tend to result in more mutations – in humans each extra year of age results in two extra mutations.

Mutation risk is linked to father's age because the sperm lineage in males keeps dividing, while females have all the eggs they are ever going to produce present at birth. Paternal age is an established risk factor in a number of disorders including schizophrenia and autism.

The study found that the number of new mutations inherited by chimpanzees from their parents is, on average, very similar to that in humans, but that the effect of the father's age is much stronger – each additional year of father's age results in three extra mutations.

The results suggest that sexual selection can influence the rate of evolution through its effect on the male mutation rate.

Professor Gil McVean, from the Wellcome Trust Centre for Human Genetics at the University of Oxford said:

"In humans, a father's age is known to affect how many new mutations he passes on to his children, and is also an established risk factor in a number of mental health disorders.”

"This study finds that in chimpanzees the father's age has a much stronger effect on mutation rate – about one and a half times that in humans. As a consequence, a greater fraction of new mutations enter the population through males, around 90 per cent, compared to humans, where fathers account for 75 per cent of new mutations."

In the study, Wellcome Trust-funded researchers sequenced the genomes of nine western chimpanzees from a three generation family living at the biomedical primate research centre in the Netherlands.

To establish the number of new mutations a child inherits researchers sequence children and their parents and compare the genetic sequence – any change in the sequence that doesn't exist in either parent genome is a new mutation. To find out which parent the mutation comes from you need to sequence members of the next generation of the family.

One explanation for this difference is that chimpanzees, as a result of their mating system, have evolved to produce many more sperm than humans – their testes are over three times the relative size of a human. This means there are likely to be more cycles of sperm production, increasing the opportunity for new mutations to emerge.

The authors suggest that more work needs to be done across other species to investigate the impact of mating behaviour on mutation rates and male mutation bias.

Source: Wellcome Trust 

Contact: Clare Ryan

Reference:

Strong male bias drives germ line mutation in chimpanzees

Oliver Venn, Isaac Turner, Iain Mathieson, Natasja de Groot, Ronald Bontrop, Gil McVean

Science 13 June 2014, Vol. 344 no. 6189 pp. 1272-1275, DOI: 10.1126/science.344.6189.1272

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ZenMaster

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For more on stem cells and cloning, go to CellNEWS at

http://cellnews-blog.blogspot.com/

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