Abstracts from the ASHG meeting

Three interesting abstracts from the American Society of Human Genetics meeting in New Orleans:

Neanderthal genomics. J. P. Noonan et al.

Our knowledge of Neanderthals is based on a very limited number of remains and associated artifacts from which we must make tenuous inferences concerning their biology, behavior and relationships to ourselves. Here we describe a new dataset with significant potential for characterising these extinct hominids from a new perspective based on the development, high-throughput sequencing and analysis of Neanderthal metagenomic libraries. The first library studied was created from the remains of a 45,000-year old Neanderthal. Multiple lines of evidence indicate the vast majority 66,643 bp of hominid sequence so far identified in the library are of neanderthal origin, the strongest being the identification of sequence changes in humans at sites where Neanderthal and chimpanzee genomic sequences are identical. These findings have enabled us to calculate the human-Neanderthal divergence time based on multiple, randomly distributed autosomal loci, in contrast to previous studies that relied on only a few mitochondrial loci. Our analyses suggest that the Neanderthal genomic sequence we obtained and the reference human genome sequence diverged diverged ~730,000 years ago. We also estimate that the ancestral populations that gave rise to the modern human and Neanderthal lineages diverged 370,000-470,000 years ago, prior to the emergence of anatomically modern humans. Based on these results, we are able to exclude a substantial Neanderthal contribution to modern human genetic diversity. In order to identify Neanderthal orthologs of human sequences of specific interest without having to sequence the entire genome, we have also developed a directed genomic selection method that we have successfully used to recover targeted sequences from Pleistocene metagenomic libraries. These studies advance our understanding of the evolutionary relationship of Homo sapiens and Homo neanderthalensis and signify the beginning of Neanderthal genomics.

Accelerated evolution of conserved noncoding sequences in the human genome. S. Prabhakar et al.

Changes in gene regulation likely influenced the profound phenotypic divergence of humans from other mammals, but the extent of adaptive substitution in human regulatory sequences remains unknown. Here we survey 129,405 conserved noncoding sequences (CNSs), which studies have revealed to be enriched in gene regulatory elements, for evidence of accelerated evolution in humans. We identified 1,119 CNSs with a statistically significant excess of human-specific substitutions after correcting for the local neutral substitution rate, the degree of CNS constraint in non-human lineages, unevenness of constraint within a CNS, and genome-wide relaxation of constraint in primates. These accelerated elements were disproportionately found near genes involved in neuronal cell adhesion. To assess the uniqueness of human noncoding evolution, we examined CNSs accelerated in chimpanzee and mouse. Although we observed a similar general trend towards neuronal adhesion in chimpanzee, the accelerated CNSs themselves exhibited almost no overlap with human, suggesting independent evolution towards different neuronal phenotypes in human s and chimpanzees. CNSs accelerated in mouse showed no bias toward neuronal cell adhesion. Our results indicate that widespread cis-regulatory changes in human evolution may have contributed to the rise of uniquely human features of brain development and function.

Estimating the split time of Human and Neanderthal populations. G. Coop, et al.

Previous genetic studies of Neanderthal ancestry have used mtDNA and thus have been limited in their conclusions on the relationship of humans and Neanderthals. We present here the first use of Neanderthal genomic DNA to assess the joint history of human and Neanderthal populations. Our data consist of 37kb of short fragments of genomic DNA sequenced in Neanderthal. By studying the degree to which modern human diversity is shared with Neanderthal we can assess the time at which the human and Neanderthal populations split. We use a flexible simulation based approach that demonstrates the power of using human variation data in such analyses. We find that the two populations split ~400,000 years ago, predating the emergence of modern humans. Our best fitting model predicts that the Neanderthal lineage will be outgroup to the human poulation ~52% of the time. 

New Scientist reports on the first and second abstracts.

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