Talking Thursday - NeanderRAD Genome News

Neanderthal DNA shown to be in 1-4 % of non-Africans. Thank God! Now all the paleoanthropologists that I've met that look like Neanderthals don't have to feel like they belong to a different species.

Here are links to people are more erudite at discussing these things and to the paper

A Draft Sequence of the Neandertal Genome - Paper #1

Targeted Investigation of the Neandertal Genome by Array-Based Sequence Capture - Paper #2

The Neandertal Genome Project - Press Info from the Max Planck Institute

Skull Caps and Genomes - The Loom

NEANDERTALS LIVE! - John Hawks

Breaking: there’s a little bit of Neandertal in all of us - Gene Expression

You're a Neanderthal: Genes say yes — a little bit - Associated Press

Friday Five #11: GWAS, Ebola, babies, and Snoop

1) Prioritizing GWAS Results: A Review of Statistical Methods and Recommendations for Their Application (Need access to read the whole article). This is an excellent review article about what to do with GWAS results or how to go about taking the next step. The authors make a good point that GWAS is the tip of the iceberg and what is really needed is a fundamental understanding of the biology involved not just the genetic variants.

Genome-wide association studies (GWAS) have rapidly become a standard method for disease gene discovery. A substantial number of recent GWAS indicate that for most disorders, only a few common variants are implicated and the associated SNPs explain only a small fraction of the genetic risk. This review is written from the viewpoint that findings from the GWAS provide preliminary genetic information that is available for additional analysis by statistical procedures that accumulate evidence, and that these secondary analyses are very likely to provide valuable information that will help prioritize the strongest constellations of results. We review and discuss three analytic methods to combine preliminary GWAS statistics to identify genes, alleles, and pathways for deeper investigations. Meta-analysis seeks to pool information from multiple GWAS to increase the chances of finding true positives among the false positives and provides a way to combine associations across GWAS, even when the original data are unavailable. Testing for epistasis within a single GWAS study can identify the stronger results that are revealed when genes interact. Pathway analysis of GWAS results is used to prioritize genes and pathways within a biological context. Following a GWAS, association results can be assigned to pathways and tested in aggregate with computational tools and pathway databases. Reviews of published methods with recommendations for their application are provided within the framework for each approach.

2) Genome Study Provides a Census of Early Humans A NYT article regarding a PNAS study that looks at the number of ancient humans around and suggest the effective population size was small, around 18,500. Basically, they looked at Alu inserts, which are a type of retroelement and are unique to primate genomes.

3) Researcher Discovers Ebola's Deadly Secret: A cool (yes I'm a nerd) Science Daily article that demonstrates how Ebola is able to fool the host cell defense mechanism and identifies the protein involved (VP35).

4) Birth Weights Fell From 1990 to 2005: Looks at a downward secular trend in the birthweight of babies. They noted that "The lower-birth-weight trend couldn't be explained by common factors such as how much weight mothers gained during pregnancy, whether the delivery was induced or by cesarean section, the amount of prenatal care, or maternal-health issues such as smoking and hypertension, researchers said". However, I wonder if they accounted for the age of the mother, which wouldn't suprise me to much if that is the case as demonstrated by this article.

5) Snoop Dogg Shocked by Genealogy Results: From Eastman's Online Genealogy Newsletter (best viewed in Firefox of Chrome). Funny but I wonder if his results will change.

Friday Five #10: Chimps, Heart Disease, and your future career

1) Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content: You had to be on Mars to miss this one this week. An article appeared in Nature that demonstrated that the Y-chromosome between Chimps and Humans was highly divergent, on the lines of 310 millions years so there is more similarity between chickens and human males (may explain my inexplicable desire to look like Colonel Sanders) then between chimps and humans. Here is the abstract.

The human Y chromosome began to evolve from an autosome hundreds of millions of years ago, acquiring a sex-determining function and undergoing a series of inversions that suppressed crossing over with the X chromosome^{1, 2}. Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. Prevailing theories hold that Y chromosomes evolve by gene loss, the pace of which slows over time, eventually leading to a paucity of genes, and stasis^{3, 4}. These theories have been buttressed by partial sequence data from newly emergent plant and animal Y chromosomes^{5, 6, 7, 8}, but they have not been tested in older, highly evolved Y chromosomes such as that of humans. Here we finished sequencing of the male-specific region of the Y chromosome (MSY) in our closest living relative, the chimpanzee, achieving levels of accuracy and completion previously reached for the human MSY. By comparing the MSYs of the two species we show that they differ radically in sequence structure and gene content, indicating rapid evolution during the past 6 million years. The chimpanzee MSY contains twice as many massive palindromes as the human MSY, yet it has lost large fractions of the MSY protein-coding genes and gene families present in the last common ancestor. We suggest that the extraordinary divergence of the chimpanzee and human MSYs was driven by four synergistic factors: the prominent role of the MSY in sperm production, ‘genetic hitchhiking’ effects in the absence of meiotic crossing over, frequent ectopic recombination within the MSY, and species differences in mating behaviour. Although genetic decay may be the principal dynamic in the evolution of newly emergent Y chromosomes, wholesale renovation is the paramount theme in the continuing evolution of chimpanzee, human and perhaps other older MSYs.

2) Telomere Length Trajectory and Its Determinants in Persons with Coronary Artery Disease: Longitudinal Findings from the Heart and Soul Study A good study that looks at telomere length and risk of cardiovascular disease. Telomeres are a good indicator of biological aging. They are basically the ends of chromosomes and as you age and the body replenishes cells through meiosis they begin to degrade.

Background

Leukocyte telomere length, an emerging marker of biological age, has been shown to predict cardiovascular morbidity and mortality. However, the natural history of telomere length in patients with coronary artery disease has not been studied. We sought to investigate the longitudinal trajectory of telomere length, and to identify the independent predictors of telomere shortening, in persons with coronary artery disease.

Methodology/Principal Findings

In a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline, and again after five years of follow-up. We used multivariable linear and logistic regression models to identify the independent predictors of leukocyte telomere trajectory. Baseline and follow-up telomere lengths were normally distributed. Mean telomere length decreased by 42 base pairs per year (p<0.001). increase =" 7.6;" years =" 1.6;" or =" 2.4;" increase =" 1.4;">

Conclusions/Significance

Leukocyte telomere length may increase as well as decrease in persons with coronary artery disease. Telomere length trajectory is powerfully influenced by baseline telomere length, possibly suggesting negative feedback regulation. Age, male sex, and abdominal obesity independently predict telomere shortening. The mechanisms and reversibility of telomeric aging in cardiovascular disease deserve further study.

3) 'Missing Link' Between Heart Failure and Environment Discovered : Similiar to the article above, this looks at the link between DNA methlyation and heart failure. Throughout most of your life certain genes or portions of genes that are not supposed to be copied are halted through methalyation or they are told you are a heart muscle cell - please stay a heart muscle cell. This is an interesting study as it indicates epigeneitic (an overused buzz word that sounds smarter than envionment).

4) U.S. Adult Obesity Still High, but Recent Data Suggest Rates May Have Stabilized A news item that mentions that obesity is still very high in the US but it seems to have stabilized, but of course this could go either way.

5) Future jobs: what might you be doing? What do you want to be in the future. Here I was hoping to do be sitting in the lab of luxury, pushing buttons ala George Jetson.

“Cultural change and biological change share the same fundamental properties of variation, selection and inheritance.” - Whitfield (2008)

“The formation of different languages and of distinct species, and the proofs that both have been developed through a gradual process, are curiously parallel” - Charles Darwin

Academically, one of my research interests is the co-evolution of genes and language. Generally, a simple observation worldwide is people who speak the same language often reproduce with each other (not always necessary but effective communication smooths the process). Based on this general observation one can assume that individuals who share a similar language will share genetic variation (see quote above).

Therefore, I was very interested in this recent feature article (view here) from PLoS Biology entitled "Across the Curious Parallel of Language and Species Evolution" by Whitfield (2008). This paper is historical in nature and starts out with Darwin (I often find if you think of a novel idea, Chucky D. thought it one hundred years ago). In an intersting parrallel I'm also wading through the first half of Janet Browne's lengthy biography, Darwin Voyaging, which is great at understanding the motivation for Darwin's love of natural history and his eventual ascendation to the thrown of biological thought. Into this Whitfield suggest evolutionary analysis will allow for a better understanding of this gene-language correlation. The author then quotes a linguist who argues that linguists may have the best case to study cultural evolution as they have the most amount of data.

Whitfield then continues to take into account similiarites between languages and genomes. First off the most important parts of a language and a genome are highly conservative but then argue that languages make huge jumps. A kind of punctuated equilibrium effect for cultural processes. He then rehashes the arguements for biological processes in brains and if there are underlying genetic correlates with different language types. Then he delves into whether or not there are parralels between culture and biology.

I think my greatest criticisms of this paper is the complete lack of an anthropological perspective (I am of course biased). Anthropology itself has long concerned itself with these questions using an evolutionary perspective. With this in mind there are a number of notable omissions within this paper. Anthropologists have been investigating the relationship between genes and language for the last 40 years at least. The father of American Anthropology, Franz Boaz, mentioned this gene-language relationship in his 1940 book Race, Language, and Culture. Early genetic work on this relationship can be traced to Cavali-Sforza and coleauges who first documented the spread of early agriculturists along with Indo-European languages. Also see Peter Bellwood's book The First Farmers for a worldwide view of this agricultural-gene-language association. In addition the article does not take into account historical linguists such as that by Joseph Greenberg, Merrit Ruhlen, Joanna Nichols, and others work into the evolution of languges.

I realize the statistical tools these individuals are using are new to quantify language differences but they are also controversial. A problem with most papers that equate cultural and biological evolution is that they assume the rate is the same. The majority of linguists believe that the deepest time one can study a language decay rate is 8,000 years. This idea is largely based on glottochronology and Joanna Nichols (1992) suggested an earlier date of around 30,000-40,000 years using a different methodology. The method that Pagel et al. (2007) use indicates a deeper time even. However, humans are a couple hundred thousand years old at best and we don't know exactly when languages show up in evolutionary history. There is good evidence that Neanderthals can speak but could Homo erectus or earlier hominins. There is also a fundamental difference between communication and language - chimps can learn language but in the wild they use elaborate communication systems to talk to each other. Is this language? even if it isn't human language.

Breast milk contains stem cells

This is via Leslie's Life Log but it is an interesting finding and from the web site Science Alert for Oceania and has important for understanding human development and the role endogenous retroviruses may play in development (more on this in a future blog).

Breast milk contains stem cells

Monday, 11 February 2008

By Catherine Madden

The Perth scientist who made the world-first discovery that human breast milk contains stem cells is confident that within five years scientists will be harvesting them to research treatment for conditions as far-reaching as spinal injuries, diabetes and Parkinson’s disease.

But what Dr Mark Cregan is excited about right now is the promise that his discovery could be the start of many more exciting revelations about the potency of breast milk.

He believes that it not only meets all the nutritional needs of a growing infant but contains key markers that guide his or her development into adulthood.

“We already know how breast milk provides for the baby’s nutritional needs, but we are only just beginning to understand that it probably performs many other functions,” says Dr Cregan, a molecular biologist at The University of Western Australia.

He says that, in essence, a new mother’s mammary glands take over from the placenta to provide the development guidance to ensure a baby’s genetic destiny is fulfilled.

“It is setting the baby up for the perfect development,” he says. “We already know that babies who are breast fed have an IQ advantage and that there’s a raft of other health benefits. Researchers also believe that the protective effects of being breast fed continue well into adult life.

“The point is that many mothers see milks as identical – formula milk and breast milk look the same so they must be the same. But we know now that they are quite different and a lot of the effects of breast milk versus formula don’t become apparent for decades. Formula companies have focussed on matching breast milk’s nutritional qualities but formula can never provide the developmental guidance.”

It was Dr Cregan’s interest in infant health that led him to investigate the complex cellular components of human milk. “I was looking at this vast complexity of cells and I thought, ‘No one knows anything about them’.”

His hunch was that if breast milk contains all these cells, surely it has their precursors, too?

His team cultured cells from human breast milk and found a population that tested positive for the stem cell marker, nestin. Further analysis showed that a side population of the stem cells were of multiple lineages with the potential to differentiate into multiple cell types. This means the cells could potentially be “reprogrammed” to form many types of human tissue.

He presented his research at the end of January to 200 of the world’s leading experts in the field at the International Conference of the Society for Research on Human Milk and Lactation in Perth.

“We have shown these cells have all the physical characteristics of stem cells. What we will do next is to see if they behave like stem cells,” he says.

If so, they promise to provide researchers with an entirely ethical means of harvesting stem cells for research without the debate that has dogged the harvesting of cells from embryos.

Further research on immune cells, which have also been found in breast milk and have already been shown to survive the baby’s digestive process, could provide a pathway to developing targets to beat certain viruses or bacteria.

Kin Selection and Aging

Kin Selection and the Evolutionary Theory of Aging
Andrew F.G. Bourke

Annual Review of Ecology, Evolution, and Systematics
Vol. 38: 103-128

Abstract:Researchers are increasingly recognizing that social effects influence the evolution of aging. Kin selection theory provides a framework for analyzing such effects because an individual's longevity and mortality schedule may alter its inclusive fitness via effects on the fitness of relatives. Kin-selected effects on aging have been demonstrated both by models of intergenerational transfers of investment by caregivers and by spatially explicit population models with limited dispersal. They also underlie coevolution between the degree and form of sociality and patterns of aging. In this review I critically examine and synthesize theory and data concerning these processes. I propose a classification, stemming from kin selection theory, of social effects on aging and describe a hypothesis for kin-selected conflict over parental time of death in systems with resource inheritance. I conclude that systematically applying kin selection theory to the analysis of the evolution of aging adds considerably to our general understanding of aging.

Darwin's Suprise: HERVs

The New Yorker has an awesome (yes I come from the 80s) article (here) on current research on endogenous retroviruses. The article gives a good run down of the background that 8% of the genome is made up of these hitchhiking viruses while only 2% of the genome causes anything. Then they go into the experiment where Thierry Heidmann brought one back to life and then mixed it with human cells where it reinserted itself into the genome and published it in the paper entitled "Identification of an Infectious Progenitor for the Multiple-Copy HERV-K Human Endogenous Retroelements". It also talks about how you can build your own virus with a labtop and a PO Box but also why it is great leap forward in our understanding of the genome. You see these viruses are not only viruses but genes and they way they insert themselves into the genome, with the enzyme reverse transcriptase, as important implications for how humans evolved but also for diseases.

Zeresenay Alemseged TedTalk

I have seen this a couple of times now (both Afarensis and Dienkes have posted) and thought I would post a link. Zeresenay Almesged is an Ethiopina paleoanthropologist who discovered Selam (in the US populary known as Lucy's Baby), which is a 3 year old almost complete hominin skeleton of A. afarensis.

Kiss my Acheulian*

I've been taking a break from the lab and teaching this week in order to recuperate for the upcoming semester, hang with the kids, and catch up on some reading that I've been neglecting. The book I just finished was The Agile Gene by Matt Ridley (originally known as Nature via Nurture) on behavioral genetics and the 20th century scientific battle between biological and environmental determinists. While the book has several interesting examples of the interaction between genes and environment and how this has led to who we are today. One of the more interesting of these factoids came from Chapter 8 "The Conundrums of Culture" and why Acheulian handaxes don't change much for 1 million years in form

Ridley recounts a hypothesis put forth by Marek Kohn (1999) that these handaxes really weren't very useful at all but simply a way of males showing off to females and the goal was to create the perfect handaxe in order to acquire the best mate. In a sense, the mental template that arose for these objects was due to sexual selection and not for utilitarian purposes. While this conjures up intriguing images of multiple males of Homo erectus happily chipping away in an elaborate flint dance, it is probably unlikely.

One problem is southeast Asia, if this is symbolic of general behavior in a species why are none of these stone handaxes found with these specimens. One is probably being selected for is not the best handaxe but the male who is best able to bring home the bacon (quite literally) . He who is the best hunter will be chosen by the females. Another problem is that it suggests that males are the only ones making stone tools. If these tools were used to process meat, then it is likely that females were involved in the scraping, chopping, and schlepping. While the acquisition of meat probably fell to the males, the distribution and consumption of meat was a group activity.

While Ridley is probably right that the interaction of our genes with our environment influencing our behavior was selected for during the Pleistocene and in order to do this you sometimes need a reductionist methodology you have to be careful to not mistake the forest for the trees.

References

Kohn, M. (1999) As We Know It: Coming to Terms with the Evolved Mind. Granta. 336 p.

Ridley M (2004) The Agile Gene: How Nature Turns on Nurture. Perennial. New York New York. 326 p.

*This title comes from the remix of an Emminen song titled"The Real Hominin" by Tony DiFiore, now it's a meme stuck in my head.