Analysis of the human microbiome reveals you are (at least related to) what you eat, in a manner of speaking

Science3Understanding microbial symbioses, and more specifically how the human microbiome affects our health, is currently a hot topic in the land of microbiology and metagenomics. The most recent special edition of Science focuses on reviews and articles centered on understanding the fundamental relationships between us and our most closely associated microbes.

Ever think that that group of people who thinks milk chocolate >> dark chocolate was a little special, well turns out they might be different for more than just that obvious reason. Some recent studies just out today have revealed that variation in the human microbiome can also be linked to differences in other food preferences.

Falony et al., 2016 / Figure 5. Drug interactions in the FGFP

Still, while we have a long way to go before we understand the significance in the variance of microbial communities a couple of articles just released in Science are some of the most extensive studies published to date on the human microbiome. The overarching goal of these impressive analyses was to try to understand what’s up with the microbes living in the large intestines of healthy individuals.

One of the studies by Falony et al., (2016) included a survey of 3,948 northern Europeans, and presents a wealth of data demonstrating that we have a long way to go before we unravel the secrets that our microbiota want to tell us…or at least what their genomes have say. All of this data might someday lead us to figuring out how we can enhance our own health by switching stuff up with our gut microbes, or how different drugs might affect different people (depending on microbial community composition).

Zhernakova et al., 2016 / Figure 2. Interindividual variation of microbial composition and function profile

There are so many variables to account for (different genetic backgrounds, ages, diets, not to mention when samples are taken post meal time…) that there’s a long way before we have a completely exhaustive dataset (is that even possible to attain??), which might be essential to figuring out health-linked stuff related to our microbiome. The other study by Zhernakova et al., (2016) looked at 1,135 Dutch individuals also demonstrated that there’s a lot we don’t know, since diversity in only 19% of the variation in the microbiome could be explained.

All of this data has led us to a bit of a chicken vs. egg situation, how much of our microbiome is influenced by genetics? or our diet? One thing is clear, affordable next-generation sequencing and the relatively recent understanding of just how essential the role our microbiome is in relation to our health will ensure that we’ll be studying our own bugs for many years to come.

References

ALEXANDRA ZHERNAKOVA, ALEXANDER KURILSHIKOV, MARC JAN BONDER, ETTJE F. TIGCHELAAR, MELANIE SCHIRMER, TOMMI VATANEN, et al. Population-based metagenomics analysis reveals markers for gut microbiome composition and diversity. Science. 352: 6285 (2016): 565-569. DOI: 10.1126/science.aad3369
 GWEN FALONY, MARIE JOOSSENS, SARA VIEIRA-SILVA, JUN WANG, YOUSSEF DARZI, KAROLINE FAUST, et al. Population-level analysis of gut microbiome variation. Science. 352: 6285 (2016): 560-564. DOI: 10.1126/science.aad3503

 

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Posted in genomics, medicine, microbiology, next generation sequencing, population genetics | Leave a comment

The slow, and sometimes incomplete, journey to diploidy

Whether you are reading this as a plant, an animal, or fungus, it is likely that some ancestor of yours doubled up on genomes. However, it is likely that these extra genomes disappeared over evolutionary time. What gives? Where are those extra genomes that I should have rightfully inherited?

Diploidization, the mysterious process that reigns extra genomes back to a diploid state, has been a vexing complexity for those who are trying to piece together the evolutionary history of ancient polyploids. For example, diploidization appears to happen at different rates at different chromosomes/loci in fish and maize.

So there are two outstanding questions. First, what taxa have undergone paleopolyploidy events? Second, how did they get back to diploidy?

 

The gradual descent into diploidy

One of the more recent whole-genome duplication events occurred in Salmonid fishes ~80 million years ago, making it a group of interest for understanding some long term evolutionary consequences of diploidization while still having enough genomic resolution to actually detect those consequences. In a recent issue of Nature, Lien et al. characterize the Atlantic Salmon genome in an attempt to document the ongoing process of diploidization in this species.

Indeed, Atlantic Salmon are still returning to diploidy:

Without exception, duplicated regions exhibiting rearrangements at telomeres in the form of inversions, translocations or larger deletions all displayed a sequence similarity of ∼87%. This clear correspondence between the degree of intra-block sequence similarity and blocks predicted to still participate in tetrasomic inheritance (or recently have done so) suggests that up to 25% of the salmon genome experienced delayed rediploidization after the initial large chromosome rearrangements, and that as much as 10% of the genome may still retain residual tetrasomy
From Figure 3c of Lien et al. (2016), displaying a hypothetical model of post genome duplication (Ss4R) rediploidization.

From Figure 3c of Lien et al. (2016), displaying a hypothetical model of post genome duplication (Ss4R) rediploidization in Atlantic Salmon.

During this process of diploidization, duplicated genes that are nonfunctional are often lost. Those functional duplicates that stick around can be the result of neofunctionalization, where one duplicate acquires a new function compared to the other, or subfunctionalization, where each duplicate retains only one part of the function from their ancestral gene. Lien et al. suggest more instances of neofunctionalization in Atlantic Salmon compared to subfunctionalization.

The predominance of cases where only one copy has changed its regulation compared to the assumed ancestral state indicates that regulatory subfunctionalization has not been a dominant duplicate retention mechanism post [genome duplication event], unless it was followed by subsequent neofunctionalization, which has been suggested as a common process.

 

When diploidization gets odd

Where the Atlantic Salmon may be steadily becoming diploid while retaining genes with new functions, another recent publication highlights a taxon in which diploidization got…odd.

The heartleaf bittercress (Cardamine cordifolia) is a widespread and ecologically-successful flowering plant in Western North America that happens to be triploid. This scenario is unusual because other triploid relatives are sterile. What makes C. cordifolia so special?

"Chromosome painting"

“Chromosome painting” is a technique to visualize happy little chromosomes using in situ hybridization

Mandakova et al. used chromosome painting to investigate the paradoxical genome number in C. cordifolia, and it turns out that the chromosome counts of C. cordifolia were not what they seemed. Due to four separate chromosome translocations, the ancestral tetraploidy of C. cordifolia has been reduced to (pseudo)triploidy in this species:

…the pseudotriploid genome of C. cordifolia originated through diploidization of a primary tetraploid ancestral genome. Hence, C. cordifolia , while being a functionally diploid species, arose from a tetraploid genome. The extant genome of C. cordifolia originated from its tetraploid progenitor through descending dysploidy, whereby the origin of four translocation (“fusion”) chromosomes reduced the original number of linkage groups from 16 to 12.

The authors justifiably conclude that chromosome counts can be misleading when interpreting the evolutionary histories of polyploid species, especially when “diploidization” doesn’t result in a diploid at all.

 

Cited

Lien, S., Koop, B. F., Sandve, S. R., Miller, J. R., Kent, M. P., Nome, T., … & Grammes, F. (2016). The Atlantic salmon genome provides insights into rediploidization. Nature. doi:10.1038/nature17164

Mandáková, T., Gloss, A. D., Whiteman, N. K., & Lysak, M. A. (2016). How diploidization turned a tetraploid into a pseudotriploid. American Journal of Botany. doi:10.3732/ajb.1500452

Posted in evolution, genomics, quantitative genetics, speciation | Tagged , , | 1 Comment

Sweeps and Demographic Inference

Population genetics presents us with numerous conundrums – several of which have to do with how the same genomic disposition can be “reached” over evolutionary time with multiple alternate demographic or selective processes. I have discussed several of these issues before (here and here), wherein demography confounds selection or vice versa. Studies that estimate genetic diversity, differentiation, and/or effective population sizes thus need to pay attention to the effects of linked selection, and sweeps before jumping to conclusions about their underlying evolutionary history. Schrider et al. (2016) in a new manuscript discuss the confounding effects of sweeps in the inference of effective population sizes using three popular evolutionary model-based inference platforms – ABC, δaδi, and PSMC.

Briefly, using coalescent simulations of 500 unlinked loci, and 100 replicate genomes under each of four population histories – constant size, bottleneck, exponential growth, and bottleneck followed by exponential growth, they determine the efficiency of genetic diversity (π), Tajima’s D, and the three methods above in recapturing the effects of linked selective sweeps of varying intensities on sites with increasing genetic distance. For inference using PSMC, the authors simulated 100 replicates of 15 Mb genomes under four scenarios – neutral, one recent sweep, three recurrent sweeps, and one of five sweeps.

Inference of effective population size change using PSMC under different scenarios of recurrent sweeps. Image courtesy: Figure 5 of Schrider et al. (2016)

Inference of effective population size change using PSMC under different scenarios of recurrent sweeps. Image courtesy: Figure 5 of Schrider et al. (2016)

Under the bottleneck model, increasing the number of loci under sweeps upwardly biased parameter estimates of effective population sizes using both δaδi, and ABC. Similarly, the population growth model simulations showed bias towards more recent and faster growth rates using both methods. Inferences were differently biased under both methods in the contraction followed by growth model as well. Inference using PSMC indicated that sweeps can influence population size change estimates considerably, depending on the number of recurrent sweeps over evolutionary time, with increased variance in estimates with increased number of sweeps, thus “dramatically skew”-ing estimates. Note however, that this is exactly what one would expect to see while using PSMC in the presence of sweeps – selective sweeps cause drastic reductions in effective population sizes, which can confound true bottlenecks (see this interesting Twitter conversation over this debate).

Rightfully so, Schrider et al. (2016) caution scientists about the challenges in “simultaneous estimation of parameters related to natural selection and demographic history”.

Until an approach to obtain accurate estimates of demographic parameters in the face of natural selection is devised, population size histories inferred from population genetic datasets could remain significantly biased.

Reference:

Schrider, Daniel, Alexander G. Shanku, and Andrew D. Kern. “Effects of linked selective sweeps on demographic inference and model selection.”bioRxiv (2016): 047019. DOI: http://dx.doi.org/10.1101/047019

Posted in bioinformatics, evolution, genomics, population genetics, selection, theory | Tagged , , , | Leave a comment

One of these things is not like the other……

...okay none of these things are very similar (courtsey wikipedia articles for: jon snow, nematodes and parrots)

While we know that bacteria are pretty scandalous with their DNA, not minding horizontal gene transfer (HGT) and such (which can be pretty confounding when trying to discuss species concepts), and although it’s clear that this kind of genetic material sharing is also important in eukaryotes, examples can be relatively more rare. Sometimes, however, some really cool and interesting cases come along….

In nature, webs of complex relationships are essential across all types of ecosystems, and, as the study points out, more and more evidence has been highlighting the role of closely associated relationships (such as that between a host and parasite) in the transfer of genetic material.

Figure 1, Suh et al., 2016

A nifty recent study published in Nature Communications from Uppsala University has published findings of fascinating transposable elements that turn up in tropical bird genomes that have only been identified in parasitic nematodes and also mammals. The group used their findings to make conclusions about the biogeography and point of occurrence of ancient host-parasite interactions. Ultimately they developed insight into the prehistoric evolutionary origins of a few human diseases, specifically lymphatic filariasis (aka elephantiasis) and loiasis, spread by mosquitoes (ugh, of course) and flies, respectively.

Figure 2, Suh et al., 2016

The transposon they identified, AviRTE, is related to a diverse group of retrotransposon-like elements (RTEs)….ah HA the acronym makes sense! This set includes a bunch of fun animals that are aquatic or reptilian. This is an interesting finding, especially given the fact that some human diseases originate from animal hosts (think about avain flu). So basically, the study found that these parasitic nematodes used to be bird parasites around 25-17 million years ago….so a LONG LONG time ago (but still in our galaxy).

Figure 3., Suh et al., 2016

One of the reasons genomic comparison studies are sooo interesting is because they can be informative in a variety of different model systems. From bacteria and archaea, to birds, nematoes, and humans…genomes can reveal interesting evolutionary histories. In the study by Suh and colleagues, it turns out that they found a pretty cool example of a parasitic animal jumping from birds to mammals.

Reference

Suh, A., Witt, C. C., Menger, J., Sadanandan, K. R., Podsiadlowski, L., Gerth, M., Weigert, A., McGuire, J. A., Mudge, J., Edwards, S. V., Rheindt, F. E. 2016. Ancient horizontal transfers of retrotransposons between birds and ancestors of human pathogenic nematodes. Nature Communications 7: 11396. http://dx.doi.org/10.1038/ncomms11396

Posted in Coevolution, evolution, genomics, horizontal gene transfer | Tagged , , , | Leave a comment

The simpler cichlid: a recent adaptive radiation

If I was asked to name a few of the most compelling systems in evolutionary biology, I’d certainly start with Darwin’s Finches. Next might come peppered moths, African cichlids, stickleback, Caribbean Anolis lizards, or Lenski’s E. coli. What’s interesting about this (very short and incomplete) list is that 4 of the 6 examples represent adaptive radiations.

Adaptive radiation is when one ancestor occupies different environments and undergoes rapid phenotypic divergence to exploit the resources of those environments (for a full discussion of the topic, read Schluter 2000). Perhaps one of the reasons adaptive radiations are so well known as evolutionary examples is because, on the surface, it is conceptually quite clear how these processes may occur. However, our understanding of the actual underlying processes is still very much in progress. Continue reading

Posted in adaptation, evolution, selection, speciation | Leave a comment

The Fourth Reviewer: More suggestions about suggesting reviewers

Tim Vines is an evolutionary ecologist who found his calling in the process of peer review. He was Managing Editor of Molecular Ecology from 2008 to 2015, launched The Molecular Ecologist in 2010, and is the founder and Managing Editor of Axios Review. Here, Tim is The Fourth Reviewer, taking on your questions about peer review and publishing. Got a question for the Fourth Reviewer? Send us an e-mail!

Should I ask people before I recommend them as reviewers on my manuscript?

Interesting question! Getting in contact with people before listing them as ‘preferred reviewers’ has never occurred to me before, but my instinct is that this is a bad idea.

Continue reading

Posted in community, peer review, science publishing, The Fourth Reviewer | Leave a comment

Island-Hopping with an E.I.D.

If you live in the U.S. and feel like Zika virus is getting closer to home, that’s because it is. Although there are no known cases of Zika transmission by natural vectors in the lower 48, experts have stressed that the virus’ spread remains unpredictable. The key word is ‘remains’ because, over the past year, Zika raced through large parts of South and Central America, leaving epidemiologists scrambling to both characterize and contain it. A conspiracy theory this is not.

In last week’s edition of Science, Faria and colleagues take an essential step in the process of describing the dynamics of this emerging infectious disease (E.I.D.). They trace the recent history of Zika virus using a dataset of new and previously reported genome sequences from across its range. Their paper also includes a large smattering of data points from Brazil, where the virus reached epidemic proportions (and surging notoriety among Western media) by mid-2015.

Correlation between airline passengers from Zika-infected countries arriving in Brazil per month versus number of suspected cases of Zika in French Polynesia on that same timescale (Figure 3C from Faria et al. 2016).

Zika virus is native to Africa and southern/southeastern Asia, and its island-hopping trek across the Pacific in an America-ward direction over the past decade has been impressive.  Continue reading

Posted in evolution, genomics, medicine, phylogenetics, Uncategorized | Leave a comment