Chenghang Zong, Sijia Lu, Alec R. Chapman and X. Sunney Xie

Science, 338:1622-6 (2012)


One of my group's research activities is the study of variations in the genomes of single cells.  Single cell genomics is a difficult avenue of study because the methods used may themselves introduce errors and variations in datasets.  One of main approaches used in single cell genomics is whole genome amplification (WGS).  WGS often introduces biases during the amplification processes.  For example, genomic regions containing a large proportion of repeated sequences or high copy number genes may be over-represented in amplified genomic DNAs. In this manuscript, Zong et al describe a new method which minimises amplification bias during the amplification of DNA from single cells.  This allows for a better assessment of natural variations in the genomic DNAs.  Using this approach, the researchers evaluated changes in the genomes of individual cancer cells.  They discovered that cancer cells had a high rate of genome-level changes.  These changes included point mutations (Single Nucleotide Variations) and changes to the number of copies of genes (Copy Number Variations).  Indeed, the researchers estimated that the cancers calls had 10 times the mutation rates of non-cancerous cells.




Kindred cells can have different genomes because of dynamic changes in DNA. Single-cell 

sequencing is needed to characterize these genomic differences but has been hindered by 

whole-genome amplification bias, resulting in low genome coverage. Here, we report on a 

new amplification method—multiple annealing and looping-based amplification cycles 

(MALBAC)—that offers high uniformity across the genome. Sequencing MALBAC-amplified 

DNA achieves 93% genome coverage ≥1x for a single human cell at 25x mean sequencing 

depth. We detected digitized copy-number variations (CNVs) of a single cancer cell. By 

sequencing three kindred cells, we were able to identify individual single-nucleotide 

variations (SNVs), with no false positives detected. We directly measured the genome-wide 

mutation rate of a cancer cell line and found that purine-pyrimidine exchanges occurred 

unusually frequently among the newly acquired SNVs.

Characterization of a scavenger receptor cysteine-rich-domain-containing protein of the starfish, Asterina pectinifera: ApSRCR1 acts as an opsonin in the larval
and adult innate immune systems

Ryohei Furukawa, Midori Matsumoto and Hiroyuki Kaneko

Developmental and Comparative Immunology 36:51–61 (2012)

Esther M Ullrich-Lütera, Sam Dupont, Enrique Arboledac, Harald Hausend and Maria Ina Arnonec

Proceedings of the National Academy of Sciences USA, 108:208367-8372 (2011)



Different sea urchin species show a vast variety of responses to variations in light intensity; however, despite this behavioral evidence for photosensitivity, light sensing in these animals has remained an enigma. Genome information of the recently sequenced purple sea urchin (

Strongylocentrotus purpuratus

) allowed us to address this question from a previously unexplored molecular perspective by localizing expression of the rhabdomeric opsin




, two genes essential for photoreceptor function and development, respectively. Using a specifically designed antibody against Sp-Opsin4 and in situ hybridization for both genes, we detected expression in two distinct groups of photoreceptor cells (PRCs) located in the animal's numerous tube feet. Specific reactivity of the Sp-Opsin4 antibody with sea star optic cushions, which regulate phototaxis, suggests a similar visual function in sea urchins. Ultrastructural characterization of the sea urchin PRCs revealed them to be of a microvillar receptor type. Our data suggest that echinoderms, in contrast to chordates, deploy a microvillar, r-opsin–expressing PRC type for vision, a feature that has been so far documented only in protostome animals. Surprisingly, sea urchin PRCs lack any associated screening pigment. Indeed, one of the tube foot PRC clusters may account for directional vision by being shaded through the opaque calcite skeleton. The PRC axons connect to the animal internal nervous system, suggesting an integrative function beyond local short circuits. Because juveniles display no phototaxis until skeleton completion, we suggest a model in which the entire sea urchin, deploying its skeleton as PRC screening device, functions as a huge compound eye.

Mark B. Gerstein,Can Bruce, Joel S. Rozowsky, Deyou Zheng, Jiang Du, Jan O. Korbel, Olof Emanuelsson, Zhengdong D. Zhang, Sherman Weissman and Michael Snyder.  

Genome Research. 17:669-681 (2007).


This is an excellent review of the vagaries of gene finding in the age of genomics.  The author begins the narrative with an overview of the historical definitions of genes and then proceeds to the current ideas of genes and their structures.  The need for new, functional definitions of genes that explain established principles of genetics, together with the newer findings of genomics, is highlighted by the ENCODE project.



While sequencing of the human genome surprised us with how many protein-coding genes there are, it did not fundamentally change our perspective on what a gene is. In contrast, the complex patterns of dispersed regulation and pervasive transcription uncovered by the ENCODE project, together with non-genic conservation and the abundance of noncoding RNA genes, have challenged the notion of the gene. To illustrate this, we review the evolution of operational definitions of a gene over the past century—from the abstract elements of heredity of Mendel and Morgan to the present-day ORFs enumerated in the sequence databanks. We then summarize the current ENCODE findings and provide a computational metaphor for the complexity. Finally, we propose a tentative update to the definition of a gene: A gene is a union of genomic sequences encoding a coherent set of potentially overlapping functional products. Our definition sidesteps the complexities of regulation and transcription by removing the former altogether from the definition and arguing that final, functional gene products (rather than intermediate transcripts) should be used to group together entities associated with a single gene. It also manifests how integral the concept of biological function is in defining genes.

© Sham Nair 2014