Tag: Disease

Disease: global & historical context

By Razib Khan | May 29, 2013 1:41 am

Citation: Corona, Erik, et al. “Analysis of the Genetic Basis of Disease in the Context of Worldwide Human Relationships and Migration.” PLoS Genetics 9.5 (2013): e1003447.

The above figure is from a paper in PLoS GENETICS, Analysis of the Genetic Basis of Disease in the Context of Worldwide Human Relationships and Migration. The authors synthesize two diverse domains of human genomics. First, there are biomedically focused genome-wide association studies and their like which attempt to identify risk alleles for particular diseases. In some cases these risk alleles are very penetrant, in that a particular state predicts with high likelihood a disease phenotype. But in most cases the yield is elevated or decreased risks for highly complex traits such as type 2 diabetes. Second, there is the domain of evolutionary genomics which attempts to reconstruct a phylogenetic and population genetic history so as to frame contemporary patterns of variation in their proper context. How this might be important or of interest is obvious in the case of malaria resistance genes. Alleles conferring resistance have arisen in multiple populations due to parallel environmental pressures. Phylogenetic relationships between these populations should inform your predictions as to the likely similarities of the mutations between the populations. Meanwhile, population genetic theory can give you clues as to the likelihood of multiple adaptations.

Read More

Kissing and cancer

By Razib Khan | May 21, 2011 11:39 pm

I recently listened to Paul Ewald talk about how a lot of cancer is due to infection on the radio show To the Best of Our Knowledge. That wasn’t too surprising, Ewald has been making the case for a connection between infection and lots of diseases for a while. What jumped out at me is his claim that kissing can spread some of the viruses. Here’s something he told Discover a few years back:

D: How do we get infected with these dangerous pathogens?

PE: Two of the most powerful examples are sexual transmission and kissing transmission, and by that I mean juicy kissing, not just a peck on the cheek. If you think about these modes of transmission, in which it might be a decade before a person has another partner, you realize that rapidly replicating is not very valuable—the winning strategy for the microbe would be to keep a low profile, requiring persistent infections for years. So we would expect that disproportionately, the sexually transmitted pathogens would be involved in causing cancer, or chronic diseases in general. You can test this. Just look at the pathogens that are accepted as causing cancer—Epstein-Barr virus, Kaposi’s sarcoma–associated herpesvirus, human T lymphotropic virus 1—and find out whether they’re transmitted this way. They almost all are. A random sample would yield maybe 15 to 20 percent of pathogens associated with cancer being sexually transmitted, yet the figure is almost 100 percent. When you look at viruses alone, it is 100 percent.

If a lot of kissing and number of sexual partners is predictive of risk of cancer, my immediate thought is that this naturally explains a lot of the cancer that  runs in families. Families can pass on genes and cultural norms which would favor or disfavor certain behaviors.

CATEGORIZED UNDER: Health
MORE ABOUT: Cancer, Disease

The evolutionary effect of the sky gods

By Razib Khan | April 24, 2011 4:02 pm

ResearchBlogging.orgLast week I reviewed ideas about the effect of “exogenous shocks” to an ecosystem of creatures, and how it might reshape their evolutionary trajectory. These sorts of issues are well known in their generality. They have implications from the broadest macroscale systematics to microevolutionary process. The shocks point to changes over time which have a general effect, but what about exogenous parameters which shift spatially and regularly? I’m talking latitudes here. The further you get from the equator the more the climate varies over the season, and the lower the mean temperature, and, the less the aggregate radiation the biosphere catches. Allen’s rule and Bergmann’s rule are two observational trends which biologists have long observed in relation to many organisms. The equatorial variants are slimmer in their physique, while the polar ones are stockier. Additionally, there tends to be an increase in mean mass as one moves away from the equator.

But these rules are just general observations. What process underlies these observations? The likely culprit would be natural selection of course. But the specific manner in which this process shakes out, on both the organismic and genetic level, still needs to be elucidated in further detail. A new paper in PLoS Genetics attempts to do this more rigorously and deeply than has been done before for one particular world wide mammalian species, H. sapiens sapiens. We have spanned the latitudes and longitudes, and so we’re a perfect test case for an exploration of the broader microevolutionary forces which shape variation.

The paper is Adaptations to Climate-Mediated Selective Pressures in Humans. Its technical guts can be intimidating, but its initial questions and final answers are less daunting. So let’s jump straight to the last paragraph of the discussion:

Read More

The city that kills you makes you strong!

By Razib Khan | September 24, 2010 12:09 am

ResearchBlogging.orgOver the past day I’ve seen reports in the media of a new paper which claims that long-term urbanization in a region is strongly correlated with genetic variants for disease resistance. I managed to find the paper on Evolution‘s website as an accepted manuscript, ANCIENT URBANISATION PREDICTS GENETIC RESISTANCE TO TUBERCULOSIS:

A link between urban living and disease is seen in recent and historical records, but the presence of this association in prehistory has been difficult to assess. If the transition to urbanisation does result in an increase in disease-based mortality, we might expect to see evidence of increased disease resistance in longer-term urbanised populations, as the result of natural selection. To test this, we determined the frequency of an allele (SLC11A1 1729 + 55del4) associated with natural resistance to intra-cellular pathogens such as tuberculosis and leprosy. We found a highly significantly correlation with duration of urban settlement – populations with a long history of living in towns are better adapted to resisting these infections. This correlation remains strong when we correct for auto-correlation in allele frequencies due to shared population history. Our results therefore support the interpretation that infectious disease loads became an increasingly important cause of human mortality after the advent of urbanisation, highlighting the importance of population density in determining human health and the genetic structure of human populations.

298px-Pericles_Pio-Clementino_Inv269In some ways this seems plausible. There are a priori reasons why we’d expect to see a great deal of evolutionary change in regions of the genome correlated with variations in immune response. Diseases are one of the most likely reasons for why sex exists in complex multicellular species; sex allows a slow-reproducing population to bend with the rapid-fire punches of their pathogens by shuffling their defenses constantly. The results from recent work mapping patterns of variation in relation to natural selection generally indicate that immune related regions show plenty of signs of adaptation. No surprise, a “Red Queen” model whereby pathogens and their hosts constantly co-evolve would imply that immunologically relevant genes would never be at equilibrium frequencies for long, so we’d have a good shot at catching “selective sweeps” on some of the immune loci.

So how do cities play into this picture? I suspect that the picture is more complicated than the presentation in the paper, though I believe that the authors were constrained by considerations of space from evaluating all possibilities in full depth. There are two facts which I think are critical to understanding the pattern of variation here:

Read More

CATEGORIZED UNDER: Anthroplogy, Culture, Human Evolution

Diseases of the Silk Road

By Razib Khan | July 26, 2010 8:42 am

behcetprev1Nature has two papers out about something called “Behçet’s disease.” It has apparently also been termed the “Silk Road Disease”, because of its associations with populations connected to the Central Eurasian trade networks.Though described by Hippocrates 2,500 years ago, apparently it was “discovered” only in the 20th century by a Turkish physician. The reason that that might be is obvious; the prevalence of Behçet’s disease is far higher in Turkey than any other nation. Two orders of magnitude difference between Northwest Europeans and Turks. East Asian populations are somewhere between Europeans and Turks, while the coverage of Inner Asia itself is thin (the first case diagnosed in Mongolia was in 2003). Additionally, the relatively similar frequency in Morocco and Iran, despite the latter nation being strong influenced by Turkic migration (25-30% of Iranian citizens are ethnically Turk), and the former not at all, leads to me wonder if there may be convergence or parallelism, rather than common ancestry, at work (or, more likely, a combination of both). The relationship between Morocco and Japan to the Silk Road in a direct fashion is tenuous at best. These were two polities which managed to be just outside the maximum expanse of Turanian empires. The Japanese famously repulsed the Mongol invasion ordered by Kublai Khan, while the Arab rulers of Morocco never fell under Ottoman control.And the early documentation by Hippocrates makes me wonder at the frequency of the disease in Greece itself. Greeks presumably contributed to the ancestry of modern Anatolian Turks, but it is far less likely because of the nature of the Ottoman system that Turks would have contributed to the ancestry of Greeks. I can’t find prevalence data for Greece, but it may be an open question in what direction the disease spread along the Silk Road.

ResearchBlogging.orgBut studies like these are nice because they are steps to overcoming one of the main issues with genome-wide associations: they use a narrow population sample, and so are not of necessary world wide relevance. Remember that even if a risk allele is not the direct cause of the disease, if it is closely associated with that alleles which are, it is of diagnostic utility. At least within that particular population. This study used groups from western and eastern Eurasia to check the power of particular single nucleotide polymorphisms (SNPs) to predict disease risk. First, Genome-wide association studies identify IL23R-IL12RB2 and IL10 as Behçet’s disease susceptibility loci:

Read More

CATEGORIZED UNDER: Genetics, Genomics, Health

Disease as a byproduct of adaptation

By Razib Khan | July 22, 2010 12:34 am

How we perceive nature and describe its shape are a matter of values and preferences. Nature does not take notice of our distinctions; they exist only as instruments which aid in our comprehension. I’ve brought this up in relation to issues such as categorization of recessive vs. dominant traits. The offspring of people of Sub-Saharan African and non-African ancestry where the non-African parent has straight or wavy hair tend to have very curly hair. Therefore, one may say that the tightly curled hair form is dominant to straight or wavy hair. But, it is also the case that there is some modification in relation to the African parent in the offspring, so the dominance is not complete. When examining the morphology of the follicle, which determines the extent of the hair’s curl, the offspring may in fact exhibit some differences from both parents. In other words our perception of the outcomes of inheritance are contingent to some extent on our categorization of the traits as well as our specific focus along the developmental pathway.

Or consider the division between “traits” and “diseases.” The quotations are necessary. Lactose intolerance is probably one of the best cases to illustrate the gnarly normative obstructions which warp our perceptions. As a point of fact lactose intolerance is the ancestral human state, and numerically predominant. It is the “wild type.” Lactose tolerance is a relatively recent adaptation, found among a variety of West Eurasian and African populations. A more politically correct term, lactase persistence, probably better encapsulates the evolutionary history of the trait, which has shifted from the class of disease to that of genetic trait when we evaluate the bigger picture (obviously diseases are simply “bad” traits”).

Read More

When sickliness is manliness

By Razib Khan | March 31, 2010 3:25 am

ResearchBlogging.orgBelow I note that sex matters when it comes to evolution, specifically in the case of how sexual reproduction forces the bits of the genome to be passed back and forth across sexes. In fact, the origin of sex is arguably the most important evolutionary question after the origin of species, and it remains one of the most active areas of research in evolutionary genetics. More specifically the existence of males, who do not bear offspring themselves but seem to be transient gene carriers is a major conundrum. But that’s not the main issue in this post. Let’s take the existence of males as a given. How do sex differences play out in evolutionary terms shaping other phenotypes? Consider Bateman’s principle:

Bateman’s principle is the theory that females almost always invest more energy into producing offspring than males, and therefore in most species females are a limiting resource over which the other sex will compete.

Female ova are energetically more expensive, and scarcer, than male sperm. Additionally, in mammals and other live-bearing species the female invests more time and energy after the point of fertilization but before the young exhibit any modicum of organismic independence (the seahorse being the exception). And, often the female is the “primary caregiver” in the case of species where the offspring require more care after birth. The logic of Bateman’s principle is so obvious when its premises are stated that it easily leads to a proliferation of numerous inferences, and many data are “explained” by its operation (in Mother Nature: Maternal Instincts and How They Shape the Human Species the biological anthroplogist Sarah Hrdy moots the complaint that the principle is applied rather too generously in the context of an important operationally monogamous primate, humans).

But the general behavioral point is rooted in realities of anatomy and life-history; in many dioecious species males and females exhibit a great deal of biological and behavioral dimorphism. But the direction and nature of dimorphism varies. Male gorillas and elephant seals are far larger than females of their kind, but among raptors females are larger. If evolution operated like Newtonian mechanics I assume we wouldn’t be theorizing about why species or sex existed at all, we’d all long ago have evolved toward perfectly adapted spherical cows floating in our own effluvium, a species which is a biosphere.

Going beyond what is skin deep, in humans it is often stated that males are less immunologically robust than females. Some argue that this is due to higher testosterone levels, which produce a weakened immune system. Amtoz Zahavi might argue that this is an illustration of the ‘handicap principle’. Only very robust males who are genetically superior can ‘afford’ the weakened immune system which high testosterone produces, in addition to the various secondary sexual characteristics beloved of film goers. Others would naturally suggest that male behavior is to blame. For example, perhaps males forage or wander about more, all the better to catch bugs, and they pay less attention to cleanliness.

But could there be a deeper evolutionary dynamic rooted in the differential behaviors implied from Bateman’s principle? A new paper in The Proceedings of the Royal Society explores this question with a mathematical model, The evolution of sex-specific immune defences:
Read More

CATEGORIZED UNDER: Evolution, Genetics, Science
NEW ON DISCOVER
OPEN
CITIZEN SCIENCE
ADVERTISEMENT

Discover's Newsletter

Sign up to get the latest science news delivered weekly right to your inbox!

Gene Expression

This blog is about evolution, genetics, genomics and their interstices. Please beware that comments are aggressively moderated. Uncivil or churlish comments will likely get you banned immediately, so make any contribution count!
ADVERTISEMENT

See More

ADVERTISEMENT

RSS Razib’s Pinboard

Edifying books

Collapse bottom bar
+

Login to your Account

X
E-mail address:
Password:
Remember me
Forgot your password?
No problem. Click here to have it e-mailed to you.

Not Registered Yet?

Register now for FREE. Registration only takes a few minutes to complete. Register now »