Sex Is Always Well Worth Its Two-Fold Cost

Title borrowed from Feigel et al. [1].

Sex is costly. In an asexual population, all individuals bear offsprings, resulting in a higher growth rate than in a sexual population (two-fold cost of sex). Finding a partner is risky, costly in terms of energy and resources, and it results in sexual selection which may not always favor survival. Finally, in sexual populations each individual passes only 50% of its genetic make-up to their offsprings and, furthermore, genetic recombination could break-up alleles that are in an epitastic relationship with one another (they are advantageous when together, but once separated they may incur into fitness loss).

However:

"The advantages of sexual reproduction stem from quite various roots. For instance, sex increases genetic variability by recombination of the parental chromosomes. It makes a population more resistant against many unpredictable threats, such as deleterious mutations, parasites, a fluctuating environment, or competing groups. It also optimizes the evolutionary search for the best gene combinations in a single individual (epistasis) [1]."

Let's try an understand this better. Different alleles in the genome are not always independent, as they may affect fitness in conjunction, a mechanism called epistasis. For example, two alleles may be beneficial together, but their benefit may be lost when separated by a recombination event. Or, it could be the other way around, that a mutation arises under certain constraints, and it's not until paired with a second mutation that it becomes beneficial. This is often observed in drug resistance, for example. A mutation that confers the organism (a virus, or a bacterium) drug resistance could potentially make it less fit (for example, if it makes the organism more "visible" to the immune system). In these cases, often one observes a new mutation arise in conjunction with the drug-resistant one, and the two together restore the organism's original fitness. These secondary mutations are called compensatory mutations because they compensate for the original loss of fitness.

Recombination of genomes can go either way: it can bring beneficial mutations together, or, it can break them apart. In a Nature Genetics review [2], the authors mention a study done on segmented viruses: in this case, "sex" is equivalent to two viruses co-infecting the same cell, as when this happens the enzyme that replicates the genes jumps back and forth between the two genomes and the resulting new genome is a reshuffle of the two parental ones. The advantage of using viruses to study the effect of sex is that you can compare the result of sexual reproduction versus asexual reproduction in the same population. In the case of the segmented virus study, it was observed that an adverse mutation was slower to get cleared in the sexual population than the asexual one.

The same review cites studies done on yeast that yielded mixed results: some showed that sex did increase the rate of adaptation of the population, and some showed the opposite. A paradox? Not quite, if you throw into the picture the size of the population.

"Two recent studies have also tested the effect of recombination on the rate of adaptation in evolving microbial populations. When populations of C. reinhardtii that initially lacked genetic variation were allowed to adapt to a novel growth medium in sexual and asexual populations of varying size, sex increased the rate of adaptation at all population sizes, but particularly in large populations [2]."

Another study done on sexual and asexual yeast strains, compared adaptation in two environments: the mouse brain, which represented a highly variable environment, and a test tube with minimal growth medium.

"When sex was induced, the sexual strain won the competition in the mouse brain but not in the test tube, despite the fact that it also showed general adaptation to this environment. These results indicate an advantage to sex during adaptation to variable or harsh environments [2]."

Despite all these studies, it is still unclear what drove the evolution of sex. Did sex prevail thanks to epistasis? Or was it just drift, the random accumulation of mutations due to pure chance? More recent studies have looked at a combination of mechanisms that may have been responsible for the rise in sexual populations. For example, other aspects to account for, besides epistasis and drift, are redundancy and genome complexity. As organisms have evolved, their genomes have increased in size and complexity. Redundancy allows for more than one gene or pathway to have same function, buffering the effect of deleterious mutations. It also maintains a reservoir of non-coding allele variants that are always available in the search for new evolutionary pathways. At the same time, sex and recombination together cause genomes to be more robust and overcome the short-term disadvantage in favor of long-term advantages like increased evolvability.

[1] Alexander Feigel,, Avraham Englander,, & Assaf Engel (2009). Sex Is Always Well Worth Its Two-Fold Cost PLoS ONE DOI: 10.1371/journal.pone.0006012

[2] J. Arjan G. M. de Visser & Santiago F. Elena (2007). The evolution of sex: empirical insights into the roles of epistasis and drift Nature Genetics Review DOI: 10.1038/nrg1985

The molecular evolution of the senses

Last week we learned that vertebrates react to smells and tastes using G-protein-coupled receptors (GPCRs), a family of proteins that "sense" molecules outside the cell surface and, depending on the molecule, activate a series of cascade events inside the cell which triggers the appropriate cellular response. This is how we distinguish good flavors from bad flavors and similarly with smells.

We also learned that tastes are not always shared across species. In fact, the genes that encode GPCRs have been turned on and off throughout evolution multiple times, allowing for example some species to be sensitive to certain tastes or smells or colors, while others aren't. How do we know?

The molecular evolution of sensory systems can be retraced by looking at two things in particular: (1) the multigene families that encode the smell, taste, and pheromone receptors; (2) pseudogenes, the remnants of once functional genes that have been silenced and/or replaced by new genes. I've talked about pseudogenes in older posts (look here and here). The DNA is often redundant and gene duplication events occur relatively frequently throughout evolution. Sometimes a copy carries a mutation that, if advantageous, may be picked up by a selective sweep. When that happens, the older, now redundant copy gets silenced and becomes a pseudogene -- a no longer coding portion of DNA. Through phylogenetic analyses, researchers can determine when these genes lost their functionality and understand how senses have evolved across species.

In [1] Emily Liman gives a beautiful example with vision: the photoreceptors in our eyes contain photopigments consisting of a GPC receptor called opsin. Humans, apes, and some primates have three distinct types of opsin, each able to maximally absorb either blue, red, or green light. This makes our vision trichromatic. Other animals like rodents, instead, are dichromatic: they only have two kinds of opsins, which maximally absorb either blue or red/green. Now, it turns out, the green opsin gene is nearly identical to the red opsin gene, making it likely that one derived from the other through a duplication event. On the other hand, humans have completely lost the capacity to detect pheromones, which is the function of the vomeronasal organ. The GPCRs in the vomeronasal organ are encoded by two gene families called V1R and V2R. Mice have 165 functional genes in the V1R family and 61 in the V24, whereas humans have 4 possibly functional genes in the former and none in the latter. However, we have roughly 200 pseudogenes in the V1R family, indicating that at some point in our evolutionary history these genes underwent a loss of function. Computational methods show that the loss of vomeronasal functionality in human evolution happened 25-40 million years ago, which happens to be the same timeline as to when trichromacy appeared.

"Interestingly, this is the same time when trichromacy appeared, suggesting that visual signaling may have replaced pheromone signaling. Indeed, catarrhine primates show prominent female sexual swelling and other sexual dimorphisms, which provide a visual signal of reproductive and social status. Thus, it is likely that as primates began to rely on these signals over chemical signals, the vomeronasal organ became redundant, and selective pressure was relaxed on molecules it uniquely expresses."

Similar observations can be made about the olfactory receptor genes: humans have 802 genes, of which ~50% are pseudogenes, versus the 25% of the 1,391 genes in the mouse, indicating that at some point in our evolutionary history selection on these genes was relaxed.

There have been evolutionary changes in taste sensation as well, and typically these changes reflect adaptive changes in diet.

"Taste allows animals to determine the nutritive content of food before ingestion: of the five identified taste modalities, three (sweet, umami, and salty) signal the presence of essential nutrients and lead to ingestive behavior. The other two modalities, bitter and sour, signal the presence of toxins or the spoilage of food, respectively, and, to most animals, are aversive."

Genes encoding the sweet receptors are well conserved across all land vertebrates with the exception of cats, whose sweet receptor T1R2 is a pseudogene (and therefore non-functional). three of the bitter receptors have become pseudogenes in humans and, furthermore, a polymorphism has been reported in the population which affects the way some of us perceive a molecule called phenythiocarbimide. This variation was also found in chimpanzee, which makes the polymorphism predate the divergence of the two species.

In conclusion,

"Expansion of the number of genes encoding sensory GPCRs has, in some cases, expanded the repertoire of signals that animals detect, allowing them to occupy new niches, while, in other cases, evolution has favored a reduction in the repertoire of receptors and their cognate signal transduction components when these signals no longer provide a selective advantage."

[1] Liman, Emily R (2006). Use it or lose it: molecular evolution of sensory signaling in primates Pflugers Arch. , 2 (453), 125-31 DOI: 10.1007/s00424-006-0120-3

The case of "junk DNA" and why it shouldn't be called junk: Redundancy.

(This is part 2 of 4 in a series dedicated to the concept of "junk DNA". Part 1 is here.)

Carl Sagan used this beautiful video to illustrate evolution:

(And Vangelis's soundtrack is the cherry on top!)

You might think that the same happens to DNA: one mutation after the other, DNA branches out just like the organisms in the video. That is not quite the case. Most of the information is saved, not erased. Why? Because that is the smart thing to do.

Mutations typically occur as random errors when cells duplicate. This often results in a new, non-functional gene. The old gene is still functioning, and the new one has a mutation that may or may not be deleterious. As mutations accumulate, things shift. The new gene may end up being functional, and, if the new mutation doesn't alter the information (what we would call a "silent" mutation), it will perform the exact same function as the old gene. That's what we call "redundancy," in other words, two or more genes sharing the same functionality. This is advantageous because if one suddenly loses its functionality, the system can revert to the old one to restore the information. It's the same mechanism used in CDs and DVDs, for example, so that you can hand them off to your kids and, unless they decide to use them as frisbees, a few scratches won't ruin your music or favorite movies.

What if the mutation was not silent and it did change the functionality of the gene?

First of all, it takes many mutations and many generations for this to happen. Sagan's video summarizes million of years in just a few minutes. But when it does happen, the new gene takes over and becomes functional. And the old gene? Still there, stored away. If you compare genes to switches, whenever a "new" gene arises, the old one is turned off and a new switch is made and turned on.

The result?

We all share most of our DNA with monkeys, giraffes, elephants, mice. What changes is which genes are "on" and which are "off." The non-functional genes that we share with other organisms are called "pseudogenes," and they are non-coding. What this means is that when DNA is unfolded and prepared for the retrieval of information to make the proteins that keep us alive, all those pseudogenes are tossed away. And that's what led to the term "junk DNA." But you see, pseudogenes have a very important role in evolution.

Imagine to toss a ball onto a rugged landscape. There are infinitely many paths the ball can take. Evolution is a rugged landscape and organisms are balls competing for the equilibrium niches. In an ever-changing landscape, saving the information can be vital. How did mammals end up back in the ocean? Because it had become advantageous and the information was already there. A few pseudogenes became functional again and the switch happened.

Again, these changes don't happen overnight. We are talking about hundreds of generations. And there is no intention behind the changes, only pure randomness driven by selection pressure from the environment. We are changing our planet a little too fast for evolution to save us. But if we had enough time, eventually our body would adapt to a CO2 laden atmosphere as the first micro-organisms that populated the Earth.

That's because Mother Nature took care of everything.

Picture: Mirror installation at the Metropolitan Museum of Art, New York. Canon 40D, focal length 66mm, exposure time 0.3 seconds.