July 05, 2013

SMBE 2013 abstracts

Some abstracts from the SMBE 2013 conference that will take place next week. 

Legacy of Early Migrants in Neolithic East Asian Hunter-Gatherer from Fukushima, Japan
K.K. Hideaki et al.   
Clarifying the genetic relationship between Neolithic East Asian Hunter-Gatherer, Jomon people, and modern human populations is one of the Keystones to understand the controversial history of modern East Asian populations. Jomon people inhabited in the Japanese archipelago from 16,000 years ago, and their origin and the relationship with modern humans have been debated for a long time. To solve these questions, we obtained 20 million base pairs of genomic DNA from a ~4,000-year-old Jomon male tooth, excavated in Sanganji shell mound, Fukushima, Japan. We compared his genetic components with the data of modern worldwide populations. Our major findings are: (1) Sanganji Jomon was very similar with modern East Asians when we compared the worldwide populations in the PCA plot; (2) when only East Asians were compared, Sanganji Jomon was distant from both modern Northeast and Southeast Asians, indicating that Sanganji Jomon people were already isolated from other continental populations for a long time; (3) the Sanganji Jomon male shared more SNP alleles with southern and northern minorities in China than geographically close Han Chinese, implying a complex history of people in China after the divergence between Jomon ancestors and Eurasian continent people; (4) Sanganji Jomon is genetically closer to modern mainland Japanese than continental populations, indicating that some of their components were transmitted to modern Japanese; (5) within Japanese archipelago, Ainu and Ryukyuan (the populations of northern and southern edges of the Japanese archipelago) have more Jomon components than mainland Japanese, indicating that the genetic effect of agricultural people who migrated from the Eurasian continent in and after the Yayoi period is stronger in Mainland Japanese than Ainu and Ryukyuan.

Extensive Gene Gain in Human Brain Evolution
Yong E. Zhang et al.
The genetic changes contributing to the evolution of the human brain have always attracted wide interest. A emerging consensus view is that while there have been no major patterns of genome-wide changes to the coding regions of brain-related genes, cis-regulatory changes of these genes have played a key role. Here, motivated by anecdotal studies of primate-specific genes implicated in brain function, we identified thousands of lineage-specific (primate-specific or rodent-specific) genes by mining syntenic vertebrate genomic alignments and examined the expression profile of these genes in both fetal and adult brains of human and mouse across different transcriptome profiling platforms. We found that an excess of lineage-specific genes are expressed in the early (fetal or infant) developing human brain compared with those in mouse brain. Expression data covering numerous subregions of the developing brain further demonstrate that these young genes are mainly transcribed in the neocortex. They originated in the evolutionary period during which the neocortex was expanding, suggesting the functional association of new genes with this newly evolving brain structure. Our data reveal that evolutionary change in the development of the human brain happened at the protein level by gene origination and also via evolution of regulatory networks, as hinted by the enrichment of primate-specific transcriptional regulators in our dataset. More than that, these ?ndings suggest that genomes are continually evolving in both sequence and content, eroding the conservation endowed by common ancestry. Despite increasing recognition of the importance of new genes, these genes are still seriously under-characterized in functional studies and that new gene annotation is inconsistent in current practice. We propose an integrative approach based on functional and evolutionary genomic methods to better annotate these non-conserved genes.

Recent Human Demography Impacts the Architecture of Genetic Disease in Populations but Not Individual Genetic Load
Yuval Simons et al.
Human populations have undergone dramatic changes in population sizes in the past 100,000 years, including a severe bottleneck of non-African populations and recent explosive population growth. There is currently great interest in how these demographic events may have affected the burden of deleterious mutations in individuals and the allele frequency spectrum of disease mutations in populations. Here we use population genetic models to show that--contrary to previous conjectures--recent human demography likely had very little impact on the average burden of deleterious mutations carried by individuals. This prediction is supported by exome sequence data showing that African American and European American individuals carry very similar burdens of damaging mutations. We next considered whether recent population growth has increased the importance of very rare mutations in disease. Our analysis predicts that, even given recent growth, it is unlikely that very rare mutations contribute a large fraction of disease heritability except for diseases that are largely due to strongly deleterious mutations. In summary, demographic history has dramatically impacted patterns of variation in different human populations, but these changes likely had little impact on either genetic load or on the importance of rare variants in most complex traits.

Functional and Population Genetic Analyses of a High-Coverage Neandertal Genome
Fernando Racimo et al.
We have sequenced the genome of a Neandertal from the Altai mountains in Siberia at 50-fold coverage. This Neandertal was located in the same cave as the Denisovan individual, but is phylogenetically closer to Neandertals from Western Eurasia. To avoid confusion, we call this individual the Altai Neandertal. Here we show an assessment of genome data quality and functional and population genetic comparisons with the Denisovan genome and a set of 25 high-coverage modern human genomes. We present an analysis of genes with recent changes in either the modern human lineage or the archaic human lineage (Neandertal+Denisova). We find enrichment for nonsynonymous changes in genes associated with melanosomes in the modern human lineage, and genes associated with particular muscoskeletal morphologies in the archaic human lineage. We utilize a compound deleteriousness scoring that allows us to combine a variety of conservation, regulatory and expression data to rank all modern and archaic-specific single-nucleotide changes and InDels across the genome, and predict which are those that could have been most disruptive in our evolutionary history. Furthermore, we overlap the modern-specific catalog with the top regions of a screen for selective sweeps exclusive to the modern human lineage, and observe enrichments for changes in genes related to ion channel activity, muscle contraction and membrane transport. Finally, we note an excess of ancestral alleles in the Denisovan individual relative to the Altai Neandertal individual, which is strongest at sites where modern humans are fixed derived. We develop an approximate Bayesian computation approach that allows us to test different models, and conclude that gene flow between the Denisovan individual and a more anciently diverged human lineage is most consistent with the patterns observed.

Multiple Episodes of Population Mixture in Southern African History
Joseph K. Pickrell et al.
The history of southern Africa involved interactions between indigenous hunter-gatherers and a range of populations that moved temporarily or permanently into the region. The influence of these interactions on the genetic structure of current populations remains unclear. Here, using patterns of linkage disequilibrium, we show that there are at least two admixture events in the genetic history of southern African hunter-gatherers and pastoralists: one involving populations related to Niger-Congo-speaking African populations, and one which introduced ancestry most closely related to west Eurasian (European or Middle Eastern) populations. We estimate that at least a few percent of ancestry in the Khoisan is derived from this latter admixture event, which occurred on average 1,200-1,800 years ago. We show that a similar signal of west Eurasian ancestry is present throughout eastern Africa; in particular, we also find evidence for two admixture events in the genetic history of several Kenyan, Tanzanian, and Somali populations, the earliest of which involved populations related to southern Europeans and which we date to approximately 2700 - 3300 years ago. We thus suggest that west Eurasian ancestry entered southern Africa indirectly through eastern Africa. These results demonstrate how large-scale genomic datasets can inform complex models of population movements, and highlight the genomic impact of largely uncharacterized back-to-Africa migrations in human history.

Mechanistic Models of Admixture and Approximate-Approximate-Bayesian Computation 
Noah Rosenberg et al.   
Investigations of the history of migrations that underlie admixed populations often use nonmechanistic admixture models rather than a modeling perspective that incorporates a population-genetic history of admixture built from first principles. We build a general model of admixture that mechanistically accounts for complex admixture processes, considering two source populations that contribute to the ancestry of a hybrid population, potentially with variable contributions across generations. For a random individual in the hybrid population at a given point in time, we study the fraction of admixture originating from a specific one of the source populations. Quite different admixture processes can produce identical mean admixture across individuals, but such processes typically produce different values for the variance of admixture. Interestingly, even without considering sex chromosomes, the variance of admixture for autosomes captures information about sex-specific migration in the contributions of the source populations to the admixed group. To perform inference under the model, we use approximate-approximate-Bayesian computation (AABC), a modification of approximateBayesian computation well-suited to estimation under complex mechanistic models that are computationally intensive to simulate. The model and inference method can contribute to an understanding of the theory and analysis of the history of admixed populations.
Inferring Human Population History and Migration Patterns from Multiple Genome Sequences
Stephan Schiffels, Richard Durbin
The availability of human genomes from populations across the world has given rise to new inference methods that exploit high-coverage sequence data. Among the most influential recent developments is the Pairwise Sequentially Markovian Coalescenct (PSMC) by Li and Durbin, 2011. While PSMC infers the demographic history for times between 20kya and 2mya with high resolution, neither the more recent evolutionary history nor migration patterns across populations can be adressed. Here we present a new method that overcomes both of these shortcomings. The Multiple Sequentially Markovian Coalescent (MSMC) infers the recent evolutionary history within and across populations only a few thousand years ago and younger. MSMC models the pattern of mutations in multiple genome sequences under the coalescent with recombination. It fits local genealogical trees to the observed pattern, focussing on the first coalescence among any two individuals. We apply our method to the genome sequences from several family trios from the 1000 Genomes project with African, European, Asian and SouthAmerican ancestry. We infer population sizes and migration rates as a function of time with high resolution. In particular, our method resolves the more recent evolutionary history of non-African populations after the out-of-Africa event, such as the peopling of the Americas.

9 comments:

Onur said...

We develop an approximate Bayesian computation approach that allows us to test different models, and conclude that gene flow between the Denisovan individual and a more anciently diverged human lineage is most consistent with the patterns observed.

a.k.a. erectus

terryt said...

Much of interest here. For example:

"there are at least two admixture events in the genetic history of southern African hunter-gatherers and pastoralists: one involving populations related to Niger-Congo-speaking African populations, and one which introduced ancestry most closely related to west Eurasian (European or Middle Eastern) populations".

That eliminates Southern Africans as being examples of early modern humans. They are just as admixed as the rest of us.

"we obtained 20 million base pairs of genomic DNA from a ~4,000-year-old Jomon male tooth, excavated in Sanganji shell mound ... (3) the Sanganji Jomon male shared more SNP alleles with southern and northern minorities in China than geographically close Han Chinese, implying a complex history of people in China after the divergence between Jomon ancestors and Eurasian continent people; (4) Sanganji Jomon is genetically closer to modern mainland Japanese than continental populations, indicating that some of their components were transmitted to modern Japanese"

The whole East Asian pattern is far from simple. We don't have a 'proto-Mongoloid' population changing gradually to a 'fully-Mongoloid' population at all.

Grognard said...

Neocortex is the most complex part of brain and much larger in neanderthals. I have to wonder how much of our intelligence comes from them. Likely the biggest "smoking gun" successful genes would be fully fixed in world population by now so it would be hard to test.

Onur said...

We don't have a 'proto-Mongoloid' population changing gradually to a 'fully-Mongoloid' population at all.

That is a non sequitur. Every race must have gone through an early phase which we can call "proto phase" in their past. The Mongoloid race is no exception. Races do not suddenly spring up; such things only happen in the Bible and other religious fantasy books and fables.

eurologist said...

"a.k.a. erectus"

Perhaps - or a very old heidelbergensis lineage mixing with a more recent one.

Grognard said...

"Perhaps - or a very old heidelbergensis lineage mixing with a more recent one."

1.2 million years ago, homo erectus was mature at 8 years old. Neanderthals were mature at the same time as humans today. The erectus in africa also had pinheads compared even to the asian homo erectus. I am not certain we are even related to homo erectus at all. When you know the story of peking man you have to wonder. No one in asia believes they evolved from erectus. It's a fad related to out of africa that looks more and more like it could simply be completely wrong.


"That is a non sequitur. Every race must have gone through an early phase which we can call "proto phase" in their past. The Mongoloid race is no exception. Races do not suddenly spring up; such things only happen in the Bible and other religious fantasy books and fables."

That is exactly how evolution works. You can have no apparent change for a billion years. It's when things happen like environment changes, that dramatic population change occurs.

Annie Mouse said...

Hhhrumph

I would love to see some decent plotting of this neanderthal specimen along with the other neanderthals, Denisovans and archaics.

In a previous paper it seemed to me that some of the "Neanderthal" genomes (including the main one used for heritory estimates ala 23 and me) were already 1/2 or 1/4 Homo sapiens (Tuscan). They had certainly diverged a long way from some of the other Neanderthal genomes in the direction of Homo sapiens.

So this paper is claiming that the Neanderthal genome found alongside the Denisovans in a cave looks like a Denisovan/archaic hybrid? Well given what we already know about the genetic similarities, the most likely archaic is the close ancestor of the Homo sapiens, Homo heidelbergensis (as Eurologist said). Neanderthal lies on the heidelgergensis/human side of the Denisovans, rather than the erectus side.

But I wonder if what we are seeing is bad data in, bad data out. If they are using a Neanderthal/Homo sapiens hybrid as a neanderthal standard, then the Homo sapiens part is going to look an archaic.

Also both these individuals were found in Siberia. The Denisovans have never been found in Africa, or Western Europe (so far).

If this Neanderthal genome is typical (and not just a stray Neanderthalish/Denisovan hybrid) then the genographics of the archaics is going to require a major review.

My best guess is that this "Neanderthal" genome will prove to be a product of a mating between a Denisovan and a Human/neanderthal hybrid (leaning towards the neanderthal side). The combination of human and neanderthal mimicking an archaic.

The alternative is that neanderthals originated in asia as a Denisovan/heidelbergensis hybrid. Before spreading into Western Europe, and back into Africa. This does not seem to fit the current state of knowledge about neanderthals.

More information needed I think.

terryt said...

"Every race must have gone through an early phase which we can call 'proto phase' in their past".

But confined within a small region, not developing in the same direction over a wide region at the same time. The spread of the Mongoloid phenotype is through gene flow, and that gene flow is basically from a single small region over a long period of time. I note that most consider Southeast Asians to be 'proto-Mongoloid' as well as the Amerindians. We can be sure that the SE Asian Mongoloid phenotype for example is a result of hybrid formation with a southward-moving population, not a product of their participation in a gradually forming Mongoloid population. The fact that Amerindians are nowhere near as 'Mongoloid' as many northern East asians is surely an indication that they too are the product of a hybrid with a more Mongoloid-looking people before they reached America.

Onur said...

But confined within a small region, not developing in the same direction over a wide region at the same time. The spread of the Mongoloid phenotype is through gene flow, and that gene flow is basically from a single small region over a long period of time. I note that most consider Southeast Asians to be 'proto-Mongoloid' as well as the Amerindians. We can be sure that the SE Asian Mongoloid phenotype for example is a result of hybrid formation with a southward-moving population, not a product of their participation in a gradually forming Mongoloid population. The fact that Amerindians are nowhere near as 'Mongoloid' as many northern East asians is surely an indication that they too are the product of a hybrid with a more Mongoloid-looking people before they reached America.

There is no evidence favoring your theory of a single small region for the origin of the Mongoloid race. We have discussed this and the Mongoloidness of Amerindians (they are clearly Mongoloid, as proven by genetics, and, also, SE Asians are much more Mongoloid than you seem to assume) in detail at another thread, so there is no reason to make the same discussion here.