Something old, something new: Evolution and the structural divergence of duplicate genes

Jan 31, 2012 by Stuart Mason Dambrot feature
The exon-intron structures of six pairs of representative sibling paralogs and the domain organization of their proteins, showing the three types of underlying mechanisms for structural divergences. Exons that have experienced exon/intron gain/loss (A-C), exonization/pseudoexonization (B-F), and insertion/deletion (B and C) events are highlighted with pink; those without structural difference are in gray. Small white bars in B and C depict the indels that have resulted from insertion/deletion events. Copyright © PNAS, doi: 10.1073/pnas.1109047109

(PhysOrg.com) -- Gene duplications are arguably the driving force of organismal evolution – and if they survive, such duplicate genes will diverge in both regulatory and coding genomic regions. Coding divergences, in turn, can be caused by nucleotide substitutions or exon-intron structural changes. (Exons are DNA bases that are transcribed into mRNA and eventually code for amino acids in proteins. Introns are DNA bases found between exons, but which are not transcribed.) Scientists have had limited knowledge in the latter case until recently, when researchers at the Institute of Botany of the Chinese Academy of Sciences investigated structural divergences during the evolution of duplicate and nonduplicate genes. They found that such structural divergences are very common in duplicate gene evolution, and have resulted from three primary causes – exon/intron gain/loss, exonization/pseudoexonization (where an intronic or intergenic sequence becomes exonic, or vice versa), and insertion/deletion – each contributing differently to structural divergence. The scientists concluded that structural divergences play a more important role in the evolution of duplicate genes than nonduplicate genes.

The research, led by Professor Hongzhi Kong and Assistant Professor Guixia Xu in the Institute of Botany’s State Key Laboratory of Systematic and Evolutionary Botany, faced three main challenges in investigating the occurrence, importance and underlying mechanisms of structural divergences during the of duplicate and nonduplicate genes.

 “The first was to identify suitable duplicate genes for comparison,” Kong told PhysOrg.com. “Not all duplicate genes, albeit abundant, could be used for this purpose – if two genes have diverged too much, it would be difficult or even impossible to make a reliable comparison between them. The second,” Kong continues, “was to generate a reasonable alignment for each gene pair based upon which the underlying mechanisms for structural divergence were determined. The third was to calculate the genetic distance between genes, especially when changes in exon-intron structure have caused shifts in reading frame.”

Kong described the ways in which the team addressed these issues. “To identify suitable duplicate genes for this study, we only considered the most closely related duplicate genes – that is, sibling paralogs – simply because their evolutionary histories were relatively short and deducible. However, the problem with this strategy is that our estimates of structural divergence were somehow conservative. Nevertheless, because differences in exon-intron structure were widespread even between sibling paralogs, our results highlighted the prevalence and importance of structural divergence during duplicate gene evolution.“

To determine the underlying mechanisms for structural divergence, it is crucial to generate a reliable alignment for each paired sibling paralogs. “However,” Kong explains, “because such work relied heavily on the annotated gene structures, we first checked and evaluated the quality of gene annotation. We found that in plants, Arabidopsis and rice were the two species whose genomes have been most extensively and carefully annotated. We therefore focused exclusively on these species at this stage. We also found that in both Arabidopsis and rice, the annotations of some genes were likely better than others, simply because they play key roles in plant development and have been the focuses of functional studies. For this reason, and because of time and labor limits, we concentrated on seven well-known gene families.”

During alignment, the team also took into consideration alternative splicing to ensure that the observed differences in exon-intron structure were not the artifact caused by comparisons of transcription forms with different splicing choices. In other words, among the multiple transcription forms of the two paralogs, only those with the same splicing choices and the highest similarity were considered. “This is also a conservative strategy that further minimized the potential errors in gene annotation.” Kong adds.

Finally, says Kong, to calculate the genetic distances between genes, they only used the regions for which homology can be determined with confidence. “When structural changes have caused shifts in reading frame,” Kong points out, “corresponding regions were no longer homologous – especially when the corresponding amino acids were considered) and thus were excluded from further analyses. This was done manually for each of the investigated gene pairs.”

Kong also discussed the team’s conclusion that structural divergences have played a more important role during the evolution of duplicate than nonduplicate genes. “Many people believe that duplicate genes tend to evolve more rapidly than nonduplicate genes because of functional redundancy,” he observes. “However, in the past few decades, attention has been paid exclusively to nucleotide substitutions, possibly because they are easy to detect and investigate. Some people even believe that point mutation, especially those that can lead to replacements of amino acids with distinct biochemical properties, play overwhelming roles in gene evolution.”

Kong also points out that there are still scattered studies showing that changes in exon-intron structure have occurred and contributed to the generation of functionally distinct paralogs and orthologs (genes in different species that evolved from a common ancestral gene by speciation). “Actually, in many recent studies – especially those that focus on the evolution of multigene families – there are plenty of cases in which duplicate genes show obvious differences in exon-intron structure. This suggests that structural divergence have been widespread and important in gene evolution. Unfortunately, up until now, an extensive investigation of the prevalence, consequences and underlying mechanisms of structural divergence has been lacking.”

In other words, the group’s study is the first to deal with the general patterns of structural divergence in gene evolution. “The conclusion that structural divergence has played a more important role during the evolution of duplicate than nonduplicate genes will help understand why gene duplication has contributed greatly to the acquisition of novel physiological and morphological characters. Clearly, duplication and subsequent divergence of genes have led to the increase of the genetic and phenotypic diversity of life.”

In Kong’s opinion, their work will have at least three impacts. “Firstly, it highlights the importance of structural divergence in gene evolution, and may induce more broad and thorough studies on the other properties of structural divergence,” he explains. “This will help understand more about the general patterns of gene evolution.”

Secondly, he continues, it will help understand the possible defects or even errors of studies in which only EST, CDS or protein sequences were compared. “As I wrote in our paper,” he notes, “‘in the future, when two or more genes are compared, special attention should be paid to their genomic sequences. Without the knowledge of exon-intron organization, it is impossible to guarantee the reliability of the alignments of genes if structural divergences, especially those that can cause shifts of reading frame, have occurred.’"

Lastly, Kong says that their findings will stimulate reconsideration of some definitions now being widely used. “During the study, we feel that the differences or boundaries between many biological terms or concepts – such as alternative splicing and exonization/pseudoexonization, and exon/intron gain/loss and exon shuffling – are not very clear. We discussed this briefly in the paper, but more efforts are needed to clarify these issues.”

In terms of next steps in their research, Kong says that the team is pursuing in two directions. “One is to investigate the prevalence and underlying mechanisms of structural divergence in representative animals, such as humans and fruit flies, and yeasts to see whether structural divergence play equally important roles in these eukaryotic lineages. From our preliminary data, we’re rather certain that this is not always the case.”

Their other focus is to investigate many other properties of structural divergence. “For example,” Kong adds, “at present we have neither calculated the occurrence rates of each mechanism for structural divergence, nor have we known whether and to what extent natural selection has contributed to the process. Also, in my lab, we focus a bit more on the genetic and molecular basis for morphological evolution. We’ve found that duplication and diversification of a few regulatory genes – mostly transcription factor – are responsible for the alterations in floral characters. We’re also carrying out functional studies to see how changes in exon-intron structure have contributed to phenotypic evolution.”

Kong adds that their research is extremely laborious and time-consuming, because most steps have to be performed manually. “It would be great if automatic pipelines could be developed to speed up the process. There’s some software that accomplishes this, but for many reasons, the quality of the work is not always satisfactory. We’re currently collaborating with developers to improve the quality and speed of such applications.”

Beyond their own research in molecular evolution, genomics, and evolutionary developmental biology, Kong concludes, the team’s research findings may benefit any other areas that have connections with these fields.

Explore further: Improving the productivity of tropical potato cultivation

More information: Divergence of duplicate genes in exon–intron structure. Published online before print January 9, 2012, PNAS January 24, 2012 vol. 109 no. 4 1187-1192, doi: 10.1073/pnas.1109047109

4.6 /5 (8 votes)

Related Stories

How research goes viral

Jan 10, 2012

Scores of interesting new findings from the biosciences may speed around the globe at the click of a mouse, but one thing particularly encourages other researchers to follow up on them: The chance to use the ...

CMS in 2011: A mountain of particle collision data

Jan 17, 2012

Datasets are the currency of physics. As data accumulate, measurement uncertainty ranges shrink, increasing the potential for discoveries and making non-observations more stringent, with more far-reaching ...

Unraveling malaria's genetic mysteries

Dec 22, 2011

(PhysOrg.com) -- Simon Fraser University researchers in biology and computing sciences are starting to piece together a picture that may help scientists and doctors save more than a million lives annually.

Watching a gas turn superfluid

Jan 18, 2012

Every time you boil water in a kettle, you witness a phenomenon known as a phase transition — water transforms from a liquid to a gas, as you can see from the bubbling water and hissing steam. MIT physicists ...

Recommended for you

Building better soybeans for a hot, dry, hungry world

19 hours ago

(Phys.org) —A new study shows that soybean plants can be redesigned to increase crop yields while requiring less water and helping to offset greenhouse gas warming. The study is the first to demonstrate ...

Gene removal could have implications beyond plant science

20 hours ago

(Phys.org) —For thousands of years humans have been tinkering with plant genetics, even when they didn't realize that is what they were doing, in an effort to make stronger, healthier crops that endured climates better, ...

Chrono, the last piece of the circadian clock puzzle?

Apr 15, 2014

All organisms, from mammals to fungi, have daily cycles controlled by a tightly regulated internal clock, called the circadian clock. The whole-body circadian clock, influenced by the exposure to light, dictates the wake-sleep ...

User comments : 1

Adjust slider to filter visible comments by rank

Display comments: newest first

aroc91
5 / 5 (2) Feb 01, 2012
hey Kevin, THIS is how information is added to the genome. I know how you always like to bring that (flawed) point up as an "argument" against evolution.

More news stories

More vets turn to prosthetics to help legless pets

A 9-month-old boxer pup named Duncan barreled down a beach in Oregon, running full tilt on soft sand into YouTube history and showing more than 4 million viewers that he can revel in a good romp despite lacking ...

Revealing camouflaged bacteria

A research team at the Biozentrum of the University of Basel has discovered an protein family that plays a central role in the fight against the bacterial pathogen Salmonella within the cells. The so cal ...

New clinical trial launched for advance lung cancer

Cancer Research UK is partnering with pharmaceutical companies AstraZeneca and Pfizer to create a pioneering clinical trial for patients with advanced lung cancer – marking a new era of research into personalised medicines ...